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Biomedical subjects

M Leone

Publications and source records attributed to M Leone.

At least 19 recordsLinked to original sources

Platelet glutamate uptake and release in migraine with and without aura.

Glutamate may play an important role in the pathogenesis of migraine: glutamate release in the brain may be involved in the development of spreading depression and increased concentrations of this amino acid have been reported in plasma and platelets from migraine patients. Here we assessed platelet glutamate uptake and release in 25 patients affected by migraine with aura (MA) and 25 patients affected by migraine without aura (MoA), comparing the results with a group of 20 healthy matched controls. Both glutamate release from stimulated platelets and plasma concentrations of the amino acid were assessed by high-performance liquid chromatography, and were increased in both types of migraine, although more markedly in MA. Platelet glutamate uptake, assessed as 3H-glutamate intake, was increased in MA, while it was reduced in MoA with respect to the control group. These results support the view that MA might involve different pathophysiological mechanisms from MoA and, specifically, up-regulation of the glutamatergic metabolism. Understanding these dysfunctional pathways could lead to new, possibly more successful therapeutic approaches to the management of migraine.

Adolescent↗

Acute hypothalamic stimulation and ongoing cluster headache attacks.

Long-term hypothalamic stimulation is effective in improving drug-resistant chronic cluster headache (CH). We assessed acute hypothalamic stimulation to resolve ongoing CH attacks in 16 patients implanted to prevent chronic CH, investigating 136 attacks. A pain intensity reduction of > or =50% occurred in 25 of 108 evaluable attacks (23.1%). Acute hypothalamic stimulation is not effective in resolving ongoing CH attacks, suggesting that hypothalamic stimulation acts by complex mechanisms in CH prevention.

Adult↗

Criticality on networks with topology-dependent interactions.

Weighted scale-free networks with topology-dependent interactions are studied. It is shown that the possible universality classes of critical behavior, which are known to depend on topology, can also be explored by tuning the form of the interactions at fixed topology. For a model of opinion formation, simple mean field and scaling arguments show that a mapping gamma'=(gamma-mu)(1-mu) describes how a shift of the standard exponent gamma of the degree distribution can absorb the effect of degree-dependent pair interactions J(ij) proportional to (k(i)k(j))(-mu), where k(i) stands for the degree of vertex i. This prediction is verified by extensive numerical investigations using the cavity method and Monte Carlo simulations. The critical temperature of the model is obtained through the Bethe-Peierls approximation and with the replica technique. The mapping can be extended to nonequilibrium models such as those describing the spreading of a disease on a network.

Journal Article↗

SOD1 gene mutations in Italian patients with Sporadic Amyotrophic Lateral Sclerosis (ALS).

Mutations in the SOD1 gene exons and exon/intron boundaries were searched in 66 sporadic and 4 familial Italian ALS cases consecutively referred to our centre from different Italian regions. A mutation was found in three sporadic cases (4.5%): a new nonsense mutation in exon 5 (K136X) in a patient with a rapid and severe disease course and two previously described missense nucleotide substitutions (N65S and A95T) in two patients with a mild disease course. Comparison of the clinical characteristics with previously reported patients carrying the same or similar mutations showed a remarkable genotype-phenotype correlation. No association was found with intronic sequence variations by comparing their frequency in the patients and in 181 matched controls.

Amyotrophic Lateral Sclerosis↗

A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort.

OBJECTIVE: To investigate the molecular genetic basis of cluster headache (CH), using a genome-wide scan and candidate gene strategy. METHODS: Northern European CH families and a case-control cohort of Danish, Swedish, and British origin (total n = 259 sporadic CH patients), including 267 control subjects matched for ancestry, participated in the study. A genome-wide genetic screen using approximately 400 microsatellite markers was performed for five informative Danish CH families. Additional markers were typed for those loci generating statistical evidence suggestive of linkage, together with genotypes for 111 individuals from further Danish and Italian kindreds. Sporadic CH patients and controls were investigated by association analysis for variation in the candidate gene, HCRTR2. Finally, complete HCRTR2 sequencing was undertaken for eight independent probands. RESULTS: Potential linkage was identified at four possible disease loci in Danish kindreds, yet no single chromosome location generated a lod or NPL score of recognized significance. No deleterious sequence variants of the HCRTR2 gene were detected by comparison to wild-type sequence. Association of the HCRTR2 gene was not replicated in this large dataset, even when the data were stratified into distinct populations. CONCLUSIONS: Cluster headache is a complex genetic disorder, with possible phenotypic and genetic heterogeneity compounding attempts at gene identification.

Adolescent↗

[What sedation for prevention and treatment secondary brain insult?].

The aim of sedation and analgesia is to prevent secondary brain insult. The goals of sedation are the prevention and treatment of intracranial hypertension and systemic disorders. In such situation, the use of sedative and analgesic therapy should respect the rate of cerebral blood flow/cerebral oxygen consumption coupling while preserving cerebral perfusion pressure and decreasing the intracranial pressure. This treatment should have an analgesic and myorelaxing action with short and predictable time of action. The optimal agent with all these characteristics does not exist, but the combination of several pharmacological compounds may reach this goal. Benzodiazepines are the most frequently agents used. In most of cases they are associated with analgesics like opioids or ketamine. Opioids are the basis of analgesia because they do not produce brain haemodynamic alterations if arterial pressure is maintained. Ketamine, which use in this indication is matter of debate, has the advantage to maintain haemodynamics. Ketamine has no side effects on brain haemodynamics when used in combination with propofol or midazolam. Because of their side effects on haemodynamics and immune response, barbituric are no longer used as long term sedative agents. However, they are still recommended in cases of refractory intracranial hypertension. Propofol remains the optimal sedative agent because of its short duration action although its use is restricted because it is an expensive drug. Its use is recommended for short time sedation with or without opioids. The use of neuromuscular blockers should be focused on the patients with an intracranial hypertension refractory to standard treatment. The presence of brain damage in patients makes difficult to assess the level of sedation. One should avoid over sedation, which increases morbidity by prolongation of the duration of mechanical ventilation.

Procedural Sedation↗

[Management of ventilator acquired pneumonia].

Ventilator-associated pneumonia occurs in the evolution of 8 to 70% of patients in the Intensive Care Unit. It is the main site of nosocomial infection for mechanically ventilated patients. Nosocomial pneumonia represents an important cause of morbidity and mortality, despite progresses in antibiotic prescription, use of intensive care and prevention. This review is based on the ATS guidelines, and reviews epidemiology, diagnosis and treatment of ventilator-acquired pneumonia, in non-immunocompromised adults.

Anti-Bacterial Agents↗

[How about blood pressure in brain injury?].

One of the goals of the medical management of head injured patients is to get a cerebral perfusion pressure between 60 and 70 mmHg. To reach such a goal, catecholamines are used after fluid challenge. Systemic effects of catecholamines depend on their affinity for the receptors alpha and beta. The topical application of norepinephrine (alpha predominant) induced a vasoconstriction on large cerebral arteries only. Cerebral blood flow increased in the pericontusionnal area, suggesting a loss of autoregulation. The topical application of dopamine at low concentration relaxed large cerebral arteries. Dopamine increased cerebral blood flow in the pericontusional area but data suggest a possible raise in the volume of contusion. Four human comparative studies have been published. The first study, which was not randomized, showed an intracranial pressure increase associated with dopamine. Two randomized clinical trials, published by the same group, demonstrated a better predictability with norepinephrine. The fourth study did not find any difference regarding cerebral haemodynamics. In conclusion, the quality of data on the effects of catecholamines on cerebral haemodynamics of head injured patients do not make it possible to conclude about their use.

Animals↗

Core percolation and onset of complexity in boolean networks.

The determination and classification of fixed points of large Boolean networks is addressed in terms of a constraint-satisfaction problem. We develop a general simplification scheme that, removing all those variables and functions belonging to trivial logical cascades, returns the computational core of the network. The transition line from an easy to a complex regulatory phase is described as a function of the parameters of the model, identifying thereby both theoretically and algorithmically the relevant regulatory variables.

Algorithms↗

Neuroimaging and pain: a window on the autonomic nervous system.

Pain is one of the most common experiences of humans. Neuroimaging techniques can visualize the main brain areas involved in pain modulation, the pain matrix. It is noteworthy that many of the brain areas forming the pain matrix are also involved in modulating autonomic nervous system (ANS) activity that in turn plays a major role in determining the best adaptive response to the pain experience. The tight connection between the pain system and ANS is also evident from neuroanatomical studies indicating that the lamina 1 neurons receive both painful and visceral stimuli from all visceral organs giving rise to the spinothalamocortical pathway concerned with conveying interoceptive information to central structures. The resulting interoceptive stream projects to the viscerosensory cortex in the mid-insula and onto the right anterior insula and orbitofrontal cortices. Right anterior insula activation is involved in the sympathetic arousal associated with mental tasks. This brain region receives numerous other inputs including pain and painful stimuli are conveyed somatotopically to both insulae. A similar somatotopic organization of painful stimuli has also been shown in the basal ganglia involved in cognitive, affective, motor and autonomic states. This highly specialized organization of nociceptive information in these brain areas may subserve a number of functions, particularly of coupling pain with the most appropriate autonomic states and affective/emotional states. The anterior cingulated cortex, another brain area playing a crucial role in nociception, is also directly involved in the control of autonomic functions such as arousal during volitional behaviour, including effortful cognitive processing. It is evident that the nociceptive system and ANS closely interact in many processes involved in maintaining internal homeostatis and in order to give the most appropriate biological substrate for cognitive, affective and emotional states.

Autonomic Nervous System↗

EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias.

Cluster headache and the other trigeminal-autonomic cephalalgias [paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome] are rare but very disabling conditions with a major impact on the patient's quality of life. The objective of this study was to give evidence-based recommendations for the treatment of these headache disorders based on a literature search and consensus amongst a panel of experts. All available medical reference systems were screened for any kind of studies on cluster headache, paroxysmal hemicrania and SUNCT syndrome. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies resulting in level A, B or C recommendations and good practice points. For the acute treatment of cluster headache attacks, oxygen (100%) with a flow of at least 7 l/min over 15 min and 6 mg subcutaneous sumatriptan are drugs of first choice. Prophylaxis of cluster headache should be performed with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy or tolerability). Although no class I or II trials are available, steroids are clearly effective in cluster headache. Therefore, the use of at least 100 mg methylprednisone (or equivalent corticosteroid) given orally or at up to 500 mg i.v. per day over 5 days (then tapering down) is recommended. Methysergide, lithium and topiramate are recommended as alternative treatments. Surgical procedures, although in part promising, require further scientific evaluation. For paroxysmal hemicranias, indomethacin at a daily dose of up to 225 mg is the drug of choice. For treatment of SUNCT syndrome, large series suggest that lamotrigine is the most effective preventive agent, with topiramate and gabapentin also being useful. Intravenous lidocaine may also be helpful as an acute therapy when patients are extremely distressed and disabled by frequent attacks.

Advisory Committees↗

Abnormal platelet trace amine profiles in migraine with and without aura.

Trace amines, including tyramine, octopamine and synephrine, are closely related to classic biogenic amines. In one study, where these substances were found elevated in plasma of migraineurs, it was hypothesized that trace amine metabolism is deranged in migraine. To confirm these findings, we studied, using a multichannel electrochemical high-performance liquid chromatography system, the concentrations of trace amines in platelets of migraine without aura (MoA) and migraine with aura (MA) patients in headache-free period, compared with controls. Platelet concentrations of trace amines, although elevated in both migraine types, showed a different profile in MoA and MA. Octopamine was significantly higher in MoA sufferers (0.69 +/- 0.43 ng/10(8) platelets) compared with both control subjects (0.22 +/- 0.16 ng/10(8) platelets) and MA patients (0.39 +/- 0.37 ng/10(8) platelets). Synephrine was significantly higher in MA patients (0.72 +/- 0.44 ng/10(8) platelets) with respect to both controls (0.33 +/- 0.25 ng/10(8) platelets) and MoA sufferers (0.37 +/- 0.29 ng/10(8) platelets). These results strengthen the hypothesis that tyrosine metabolism is deranged in migraine and may participate in its pathophysiology.

Adolescent↗

[A case of type A botulism].

The neurotoxin produced by Clostridium botulinum, is responsible for botulism. The clinical signs are digestive disorders, pupillar alterations, and peripheral muscular weakness. The failure of thoracic muscles is responsible for the severity of botulism. We describe a case of a 74 year old woman who presented a severe form of botulism, requiring a prolonged intensive care unit stay.

Aged↗

Predictive perioperative factors for developing severe sepsis after major surgery.

BACKGROUND: Early identification of high-risk patients undergoing major surgery can result in an aggressive management affecting the outcome. METHODS: We designed a prospective cohort study of 93 adult patients undergoing major oncological surgery to identify the predictive risk factors for developing postoperative severe sepsis. RESULTS: Nineteen of 93 patients developed a severe sepsis after surgery; seven of the septic patients died in intensive care unit. Multivariate analysis discriminated preoperative and postoperative (first and second day after surgery) predictive risk factors. The postoperative severe sepsis was independently associated with preoperative factors like male gender (OR 4.7, 95% CI between 1.5 and 15.5, P<0.01) and Charlson co-morbidity index (OR 1.3, 95% CI between 1.07 and 1.6, P<0.01). After the surgery, the presence of systemic inflammatory response syndrome (OR 4.0, 95% CI between 1.02 and 15.7, P<0.05) and a logistic organ dysfunction score on day 2 (OR 3.3, 95% CI between 1.9 and 5.7, P<0.001) were found as independent predictive factors. CONCLUSION: We have shown that some of the markers that can be easily collected in the preoperative or postoperative visits can be used to screen the patients at high risk for developing severe sepsis after major surgery.

Adult↗

Trading interactions for topology in scale-free networks.

Scale-free networks with topology-dependent interactions are studied. It is shown that the universality classes of critical behavior, which conventionally depend only on topology, can also be explored by tuning the interactions. A mapping, gamma'=(gamma-mu)/(1-mu), describes how a shift of the standard exponent gamma of the degree distribution P(q) can absorb the effect of degree-dependent pair interactions J(ij)proportional to(q(i)q(j))(-mu). The replica technique, cavity method, and Monte Carlo simulation support the physical picture suggested by Landau theory for the critical exponents and by the Bethe-Peierls approximation for the critical temperature. The equivalence of topology and interaction holds for equilibrium and nonequilibrium systems, and is illustrated with interdisciplinary applications.

Journal Article↗

The role of the ear, nose and throat specialist in diagnosing headaches.

The revised International Headache Society classification (2004) represents a very good reference also for ear, nose and throat (ENT) specialists and can be largely shared. The authors follow the classification outline and comment on the chapters of ENT interest. The classification leaves unsolved problems and most of them are of ENT competence, such as mucosal contact point headache. It will be a task for ENT specialists to clarify the real role of very hypothetical primary forms frequently assigned to diagnosis without a correct rationale.

Ear↗