Fabio Colombo

Presurgical identification of hibernating myocardium by combined use of technetium-99m hexakis 2-methoxyisobutylisonitrile single photon emission tomography and fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography in patients with coronary artery disease

We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-d-glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary arterybypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13 %) was estimated in the segments with no 18F-FDG uptake. Despite the potential limitations due to the semiquantitative analysis of the images, the method appears to provide reliable information for the diagnostic and prognostic evaluation of patients with CAD undergoing CABG and confirms that the identification of hibernating myocardium with 18F-FDG is of paramount importance in the diagnosis of patients undergoing CABG.

Metabolic Impairment in Human Amnesia: A PET Study of Memory Networks

Human amnesia is a clinical syndrome exhibiting the failure to recall past events and to learn new information. Its “pure” form, characterized by a selective impairment of long-term memory without any disorder of general intelligence or other cognitive functions, has been associated with lesions localized within Papezs circuit and some connected areas. Thus, amnesia could be due to a functional disconnection between components of this or other neural structures involved in long-term learning and retention. To test this hypothesis, we measured regional cerebral metabolism with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) and positron emission tomography (PET) in 11 patients with “pure” amnesia. A significant bilateral reduction in metabolism in a number of interconnected cerebral regions (hippocampal formation, thalamus, cingulate gyrus, and frontal basal cortex) was found in the amnesic patients in comparison with normal controls. The metabolic impairment did not correspond to alterations in structural anatomy as assessed by magnetic resonance imaging (MRI). These results are the first in vivo evidence for the role of a functional network as a basis of human memory.

Errors Introduced by Tissue Heterogeneity in Estimation of Local Cerebral Glucose Utilization with Current Kinetic Models of the [18F]Fluorodeoxyglucose Method

The effects of tissue heterogeneity on the estimation of regional cerebral glucose utilization (rCMRglc) in normal humans with [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) and positron emission tomography (PET) were compared with respect to the various kinetic models of the [18F]FDG method. The kinetic models were conventional homogeneous tissue models of the [18F]FDG method, with (4K Model) and without (3K Model) a rate constant to account for an apparent loss of [18F]2-fluoro-2-deoxy-d-glucose-6-phosphate ([18F]FDG-6-P), and a tissue heterogeneity model (TH Model). When either of the kinetic models designed for homogeneous tissues was applied to heterogeneous tissues, estimates of the rate constant for efflux of [18F]FDG from the tissue (k*2) and of the rate constant for phosphorylation of [18F]FDG (k*3) decreased as the duration of the experimental period was increased. When the 4K Model was used, estimates of the rate constant for the apparent dephosphorylation of [18F]FDG-6-P (k*4) were significantly greater than zero and fell with increasing duration of the experimental period. Although the TH Model included no term to describe an apparent dephosphorylation of [18F]FDG-6-P, the fit of the TH Model to the time course of total tissue radioactivity was at least as good as and often better than the fit of the 4K Model in the 120-min period following the pulse of [18F]FDG. Hence, the high estimates of k*4 found in PET studies of ≤120 min can be explained as the consequence of measuring radioactivity in a heterogeneous tissue and applying a model designed for a homogeneous tissue; there remains no evidence of significant dephosphorylation of [18F]FDG-6-P in this time period. Furthermore, use of the 4K Model led to an overestimation of rCMRglc; whole-brain glucose utilization calculated with the 4K Model was >20% higher than values usually obtained in normal humans by the model-independent Kety–Schmidt technique. rCMRglc was accurately estimated by the TH Model and, in experimental periods sufficiently long to minimize the effects of tissue heterogeneity, also by the original 3K Model of the deoxyglucose method.

Biodistribution of Tc-99m methoxy-isobutyl-isonitrile (MIBI) in humans

Hexakis (methoxyisobutilisonitrile) technetium(I), 99mTc-MIBI, has been proposed for myocardial perfusion studies. We have evaluated the biodistribution of this new agent in normal volunteers at rest and after stress. The biodistribution of 99mTc-MIBI is characterized by rapid blood clearance and a consequently early myocardial uptake. The initial intense hepatic activity is cleared into the gallbladder at 1 h after injection, and the best target to non target ratio is observed at 60–90 min after injection. Absorbed radiation dose calculations show that the thyroid is the critical target organ (230 mRad/mCi at rest), presumably because of 99mTc-pertechnetate generated in vivo. Our results indicate that 99mTc-MIBI is a promising tracer for myocardial perfusion imaging.

Buffalo meat as a salted and cured product

Bresaola, a GPI product, is produced by salting and curing different cuts of the hindquarters of lean bovine meat. The use of buffalo meat to produce similar processed, cold-cut products demonstrated the possibility of transforming cuts of buffalo rump into a product similar to that of beef, even considering parameters that penalise the buffalo product like tenderness and colour.

Treatment and control of arterial hypertension in a rural community in Ecuador

Cardiovascular diseases are widespread in developing countries, but little is known about cardiovascular risk profiles in rural communities. To assess the importance of arterial hypertension in a rural district of Ecuador, we screened 4284 of the 8876 adults who lived in the area. 1542 (36%) individuals had hypertension, only four (0.3%) of whom were well controlled by treatment. We monitored all deaths for 2.5 years, and noted that cardiovascular diseases were the primary cause of death in the adult population. Furthermore, of the individuals who died of a cardiovascular disease, four out of five had a history of hypertension. Our findings indicate that in this rural area of Ecuador the high prevalence of uncontrolled hypertension is a major cause of total mortality.

Time dependence of residual tissue viability after myocardial infarction assessed by [18F]fluorodeoxyglucose and positron emission tomography

Areas of myocardial infarction may retain glycolytic activity and this finding is indicative of tissue viability and predictive of functional recovery after revascularization. In order to assess the relation between the time elapsed from the occurrence of acute myocardial infarction and persistence of myocardial metabolic activity in the infarcted tissue, we prospectively studied 65 patients with previous myocardial infarction diagnosed clinically and by electrocardiographic (Q wave) and enzymatic criteria. All patients underwent coronary angiography and contrast left ventriculography, evaluation of regional myocardial glucose metabolism (in the fasting state) by positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and assessment of myocardial perfusion by single photon emission computed tomography (SPECT) with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI). Based on the regional metabolic and perfusion findings, patients were divided into 2 groups, depending on the absence (group 1, 26 patients) or presence (group 2, 39 patients) of [18F]FDG uptake in the underperfused regions. Areas of underperfusion at rest, consistent with the clinically identified myocardial infarction site, were observed in all patients. Severity of coronary artery disease, presence of collaterals, number of hypocontractile segments, and wall motion score did not differ significantly in the 2 groups. The time elapsed from the infarction was significantly greater (1,860 +/- 1,333 days) in group 1 than in group 2 (92 +/- 115 days; p < 0.0001). Exercise caused an increase in severity and/or extent of resting perfusion abnormalities in a greater proportion of patients of group 1 (53% vs 23%).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term vitamin E supplementation fails to reduce lipid peroxidation in people at cardiovascular risk: analysis of underlying factors

BackgroundAntioxidant supplementation with vitamin E had no effect in the prevention of cardiovascular diseases (CVD) in three recent large, randomized clinical trials. In order to reassess critically the role of vitamin E in CVD prevention, it is important to establish whether these results are related to a lack of antioxidant action.MethodsWe examined the in vivo antioxidant effect of vitamin E (300 mg/day for about three years) in 144 participants in the Primary Prevention Project (females and males, aged ≥ 50 y, with at least one major CV risk factor, but no history of CVD). Urinary 8-epi-PGF2α (isoprostane F2α-III or 15-F2t-isoP), a validated biomarker of lipid peroxidation, was measured by mass spectrometry.ResultsUrinary excretion of 8-epi-PGF2α [pg/mg creatinine, median (range)] was 141 (67–498) in treated and 148 (76–561) in untreated subjects (p = 0.10). Taking into account possible confounding variables, multiple regression analysis confirmed that vitamin E had no significant effect on this biomarker. Levels of 8-epi-PGF2α were in the normal range for most subjects, except smokers and those with uncontrolled blood pressure or hyperglycemia.ConclusionsProlonged vitamin E supplementation did not reduce lipid peroxidation in subjects with major cardiovascular risk factors. The observation that the rate of lipid peroxidation was near normal in a large proportion of subjects may help explain why vitamin E was not effective as an antioxidant in the PPP study and was ineffective for CVD prevention in large scale trials.

Identification of Penicillium aurantiogriseum species with a method of polymerase chain reaction-restriction fragment length polymorphism

Abstract A polymerase chain reaction method, added of restriction fragment length polymorphism analysis, was utilised to identify moulds, isolated from foods, belonging to Penicillium aurantiogriseum species. Suitable restriction enzymes were found. This simple method could be useful to face mycotoxin problem, discriminating toxic from non-toxic strains.

Computer-assisted evaluation of isoelectric focusing patterns in electrophoretic gels: identification of smoothhounds (Mustelus mustelus, Mustelus asterias) and comparison with lower value shark species.

In this work, the most commercially important Selachian species, smoothhound (Mustelus mustelus) and starry smoothhound (Mustelus asterias), have been identified by polyacrylamide isoelectric focusing (IEF‐PAGE), along with several shark species of minor commercial value. In Italy, these two smoothhound species are commonly subjected to fraudulent substitution with lesser valued sharks. After the electrophoretic runs, the band patterns of the two Mustelus species were compared with those of dogfish (Scyliorhinus canicula), spurdog (Squalus acanthias), blue shark (Prionace glauca) and black‐mouthed dogfish (Galeus melanostomus), both visually and with gel analysis software. The actual isoelectric points were then submitted to cluster analysis to differentiate the single species, despite the possible occurrence of electrophoretic variations or protein polymorphism. Every shark showed species‐specific band patterns and could therefore be well differentiated, as confirmed by statistical analysis.