Positron Emission Tomography in Acute Coronary Syndromes

Several imaging techniques have been used to assess cardiac structure and function, to understand pathophysiology, and to guide clinical decision making in the setting of acute coronary syndromes (ACS). Over the last years, cardiac positron emission tomography (PET) has affirmed its role in this setting. Indeed, the combined quantitative assessment of myocardial metabolism and perfusion has allowed to better understand the functional status of infarcted and non-infarcted myocardium, thus improving our knowledge of myocardial response to necrosis. More recently, several studies, taking advantage of previous observations in patients with cancer, have shown that PET could also provide important information on the mechanisms of vascular instability through the early identification of activated inflammatory cells in the atherosclerotic plaque. These findings are opening the way to more effective forms of prevention of acute vascular syndromes in high-risk patients; furthermore, new more sensitive and specific tracers for the identification of vascular inflammation are under development. In this review, we describe the potential and limitations of PET in the assessment of ACS.     

Depression, hypertension, and comorbidity: Disentangling their specific effect on disability and cognitive impairment in older subjects

We aimed to demonstrate that depression and hypertension are associated independently of each other with disability and cognitive impairment in older subjects and that such an association is not attributable to number and severity of comorbidities. An observational study was performed on elderly patients admitted to the Hospital Network of the Italian National Research Center on Aging (INRCA) from January 2005 to December 2006. Depression was defined according to 15-item geriatric depression scale (GDS) score; physical disability according to activities of daily living (ADL) and instrumental activities of daily living (IADL) scores; cognitive impairment on the mini-mental state examination (MMSE) test; the number and severity of comorbidities by means of physician-administered cumulative illness rating scale (CIRS). Among 6180 older subjects (age = 79.3 ± 5.8 years; 47% men), 48.3% were normotensive, 21.8% normotensive depressed, 21.7% hypertensive, and 8.2% hypertensive and depressed. Both depression and hypertension remained significantly associated with functional disability and cognitive impairment. When controlling for age, gender, the number and severity of comorbidities, hypertension was associated with a significantly higher likelihood of having functional disability or cognitive impairment only in the presence of depression (odds ratio = OR = 2.02, 95% confidence interval = 95%CI = 1.60-2.54, p < 0.001 for functional disability; OR = 2.21, 95%CI = 1.79-2.74, p < 0.001 for cognitive impairment) as compared to normotensive controls without depression. We conclude that depression per se’ or co-occurrence of hypertension and depression is associated with higher functional disability and cognitive impairment in older subjects. This effect is not attributable to the number or to the severity of comorbidities.     

Origin of facilitation of motor-evoked potentials after paired magnetic stimulation: direct recording of epidural activity in conscious humans

A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below active threshold for obtaining motor-evoked potentials (MEPs) facilitates EMG responses evoked at rest in hand muscles by a suprathreshold magnetic stimulus given 10-25 ms later. This is known as intracortical facilitation (ICF). We recorded descending volleys produced by single and paired magnetic motor cortex stimulation through high cervical epidural electrodes implanted for pain relief in six conscious patients. At interstimulus intervals (ISIs) of 10 and 15 ms, although MEP was facilitated, there was no change in the amplitude or number of descending volleys. An additional I wave sometimes was observed at 25 ms ISI. In one subject, we also evaluated the effects of reversing the direction of the induced current in the brain. At 10 ms ISI, the facilitation of the MEPs disappeared and was replaced by slight suppression; at 2 ms ISI, there was a pronounced facilitation of epidural volleys. Subsequent experiments on healthy subjects showed that a conditioning stimulus capable of producing ICF of MEPs had no effect on the EMG response evoked by transmastoidal electrical stimulation of corticospinal tract. We conclude that ICF occurs because either 1) the conditioning stimulus has a (thus far undetected) effect on spinal cord excitability that increases its response to the same amplitude test volley or 2) that it can alter the composition (but not the amplitude) of the descending volleys set up by the test stimulus such that a larger proportion of the activity is destined for the target muscle.     

Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans

Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA_A receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA_A activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA_A activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI  ( F _3,9= 3.19, P = 0.039)  . In contrast to SICI, SAI was significantly reduced by lorazepam  ( F _3,9= 9.39, P = 0.0002)  . Our findings demonstrate that GABA_A activity enhancement determines a suppression of SAI and an increase of SICI.     

Dissociated effects of diazepam and lorazepam on short-latency afferent inhibition

Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short-latency afferent inhibition, SAI). This can be tested by coupling electrical stimulation of peripheral nerve with transcranial magnetic stimulation (TMS) of the motor cortex. SAI is reduced by the anticholinergic drug scopolamine, and in patients with Alzheimer's disease. Therefore, it is possible that SAI is a marker of central cholinergic activity important for memory function. The benzodiazepine lorazepam also reduces SAI. Since benzodiazepines impair memory formation, but do not do so uniformly, with a maximum amnesic effect after lorazepam but less or no effect after diazepam, we were interested in testing in this non-behavioural study to what extent the effects of lorazepam and diazepam on circuits involved in SAI could be dissociated. In addition, and for control, we tested the effects of lorazepam and diazepam on short-interval intracortical inhibition (SICI), a motor cortical inhibition mediated through the GABA_A receptor. Lorazepam markedly reduced SAI, whereas diazepam slightly increased it. In contrast, both benzodiazepines uniformly increased SICI. Our findings demonstrate opposite effects of lorazepam and diazepam on SAI, an inhibition modulated by central cholinergic activity, but the same effects on SICI, a marker of neurotransmission through the GABA_A receptor. This dissociation suggests, for the first time, that TMS measures of cortical inhibition provide the opportunity to segregate differences of benzodiazepine action in human central nervous system circuits.     

Modulation of motor cortex neuronal networks by rTMS: comparison of local and remote effects of six different protocols of stimulation

Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS depend critically on stimulus frequency. The aim of our present study was to compare the effects of different rTMS protocols. We compared the aftereffects of 6 different rTMS protocols [paired associative stimulation at interstimulus intervals of 25 (PAS(25)) and 10 ms (PAS(10)); theta burst stimulation delivered as continuous (cTBS) or intermittent delivery pattern (iTBS); 1- and 5-Hz rTMS] on the excitability of stimulated and contralateral motor cortex in 10 healthy subjects. A pronounced increase of cortical excitability, evaluated by measuring the amplitude of motor evoked potentials (MEPs), was produced by iTBS (+56%) and PAS(25) (+45%). Five-hertz rTMS did not produce a significant increase of MEPs. A pronounced decrease of cortical excitability was produced by PAS(10) (-31%), cTBS (-29%), and 1-Hz rTMS (-20%). Short-interval intracortical inhibition was suppressed by PAS(10). Cortical silent period duration was increased by 1-Hz stimulation. No significant effect was observed in the contralateral hemisphere. Head-to-head comparison of the different protocols enabled us to identify the most effective paradigms for modulating the excitatory and inhibitory circuits activated by TMS.     

Worrisome Trend of New Multiple Mechanisms of Linezolid Resistance in Staphylococcal Clones Diffused in Italy

In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (cfr, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).     

Cerebral arteriovenous malformations (CAVM)]

Two infants with endocranic A-V malformations and irreversible picture of congestive cardiac failure are presented: the first is a newborn with a very large angioma, the second is a newborn with a large aneurysm of the vein of Galen. A review of the literature is presented: the salient age-related features required to make a diagnosis are discussed.