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Biomedical subjects

G Micieli

Publications and source records attributed to G Micieli.

At least 37 records · Page 2Linked to original sources

Simulation of a stroke unit careflow.

This paper describes the development and use of a simulation model representing part of the medical practice within a Stroke Unit. In particular, we modelled the medical activities as described in a guideline for the ischemic stroke treatment, adopted by the Stroke Unit of our hospital. The Petri net formalism has been chosen for the model representation. The numerical parameters have been estimated both using a database of about 100 patients collected during the last two years, and eliciting knowledge from the neurologists. A commercial tool was used for performing simulations, while ad-hoc routines were written for tailoring the result presentation to the specific context. We consider simulation a very useful preliminary step for the subsequent implementation of a patient workflow (careflow) management system. In fact, simulation is based on the process model (the clinical practice guideline) and on the organisation model (human and technological resources), so allowing to detect bottlenecks in the care delivery organisation and to find the optimal resource allocation. For example, we show that simulation has been able to find some of the causes of the delay in the patients treatment, and accordingly, to suggest changes in the organisation.

Brain Ischemia↗

Guideline-based careflow systems.

This paper describes a methodology for achieving an efficient implementation of clinical practice guidelines. Three main steps are illustrated: knowledge representation, model simulation and implementation within a health care organisation. The resulting system can be classified as a 'guideline-based careflow management system'. It is based on computational formalisms representing both medical and health care organisational knowledge. This aggregation allows the implementation of a guideline, not only as a simple reminder, but also as an 'organiser' that facilitates health care processes. As a matter of fact, the system not only suggests the tasks to be performed, but also the resource allocation. The methodology initially comprehends a graphical editor, that allows an unambiguous representation of the guideline. Then the guideline is translated into a high-level Petri net. The resources, both human and technological necessary for performing guideline-based activities, are also represented by means of an organisational model. This allows the running of the Petri net for simulating the implementation of the guideline in the clinical setting. The purpose of the simulation is to validate the careflow model and to suggest the optimal resource allocation before the careflow system is installed. The final step is the careflow implementation. In this phase, we show that the 'workflow management' technology, widely used in business process automation, may be transferred to the health care setting. This requires augmenting the typical workflow management systems with the flexibility and the uncertainty management, typical of the health care processes. For illustrating the proposed methodology, we consider a guideline for the management of patients with acute ischemic stroke.

Artificial Intelligence↗

Doppler sonography to monitor flow in different cerebral arteries in the rabbit.

Most of the transcranial Doppler (TCD) experimental studies on cerebral haemodynamics have been performed in the rabbit because of the similarity between its Willis circle and that of the human, but these studies have mainly been limited to the basilar artery. The present study was aimed at extending the use of TCD sonography to all other large cerebral arteries. In anaesthetised rabbits, these arteries were insonated from three different recording sites, i.e. top-cranial, suboccipital and orbital, using a two-channel pulsed Doppler device equipped with 4 and 8 MHz probes. First, discrimination between intra- and extracranial arteries was achieved through a standard 'rebreathing' test (hypercapnic-hypoxic stimulation). The distinctive blood velocity response patterns, reflecting the different extents of metabolic reactivity in intra- and extracranial territories, are described and discussed. Intracranial arteries were then identified on the basis of their response to ipsi- and contralateral common carotid artery occlusion. This procedure allowed recording from the following arteries: anterior common trunk, anterior cerebral, internal carotid, middle cerebral and basilar; the latter could be simultaneously monitored with any of the others. This study provides an experimental model allowing investigation of regional differences in the haemodynamic response to neurogenic and pharmacological stimuli.

Animals↗

Vasomotor response to CO2 and L-Arginine in patients with severe internal carotid artery stenosis; pre- and post-surgical evaluation with transcranial Doppler.

BACKGROUND AND AIM: Carotid artery disease may cause both thromboembolism and cerebral blood flow disturbances, particularly in subjects with impaired hemodynamic compensatory mechanisms. The aim of this study was to evaluate by transcranial Doppler (TCD) the hemodynamic changes induced by CO2 and L-Arginine stimulation in a selected population with severe unilateral carotid stenosis (70-80%), before and after carotid endarterectomy, in order to determine the effect of surgery in the vascular hemodynamics of these patients. METHODS: We studied 20 subjects (mean age 66.4 years) consecutively admitted to our institute with ischemia and unilateral severe internal carotid artery stenosis (70-80%) detected by Color Doppler. All patients underwent arterial digital subtraction angiography to confirm the ultrasonographic evaluation. TCD was performed bilaterally; blood flow velocity was monitored during CO2 and L-Arginine stimulation both in basal conditions and three months after surgery. RESULTS: After endarterectomy, mean velocity increased in response to both stimuli with a trend toward statistical significance. A significantly lower reactivity to L-Arginine on the stenotic side was found in the pre-operative phase: this asymmetrical reactivity was no longer observable after carotid endarterectomy. CONCLUSIONS: We found a statistically significant difference in L-Arginine reactivity in the stenotic side of patients with severe unilateral internal carotid stenosis. This is probably related to an alteration of the endothelium function due to the carotid pathology, since the abnormalities disappeared three months after endarterectomy.

Aged↗

Alpha-dihydroergocryptine in the prophylaxis of migraine: a multicenter double-blind study versus flunarizine.

This multicenter, double-blind, clinical study was designed to compare the efficacy and safety of alpha-dihydroergocryptine and flunarizine in the prophylaxis of migraine without aura. One hundred thirty-five patients fulfilling the diagnostic criteria of the International Headache Society were enrolled at five neurologic centers. The study design included a 1-month pretreatment phase with placebo; a 6-month, double-blind, double-dummy treatment phase with alpha-dihydroergocryptine (10 mg twice daily) or flunarizine (5 mg once daily); a further 3-month follow-up phase without treatment. Efficacy was assessed using the patient's diary. Laboratory tests, vital signs, and adverse events were monitored. Analysis of covariance for repeated measures was performed on the intent-to-treat sample. Both treatments led to a significant reduction in the frequency of migraine, days with headache, and use of relief medication. Overall, 51% of those treated with alpha-dihydroergocryptine and 49% of those treated with flunarizine were responders (50% or greater reduction in attack frequency), the average percentage of reduction being 64% with alpha-dihydroergocryptine and 51% with flunarizine. There was no significant difference between the two groups in terms of incidence of adverse events; dizziness and weight gain were the most frequent observed adverse events with alpha-dihydroergocryptine and flunarizine, respectively. Based on the overall improvement in migraine parameters, alpha-dihydroergocryptine can be recommended for use in migraine prophylaxis.

Adult↗

Bromocriptine test in the evaluation of patients with syncope of unknown aetiology. A case-control study.

The aim of the present study was to evaluate, through a case-control study, the specificity of the upright tilt test with bromocriptine as a marker of neurally mediated syncope of unknown aetiology. We have compared upright tilt test with bromocriptine (2.5 mg p.o.) in patients with syncope of unknown aetiology and controls. A total of 23 patients and controls matched by age and sex had upright tilt test with bromocriptine. The upright tilt test procedure consisted of 10 min in supine position, 10 min of 60 degree head-up tilt and a further 10 min with the subject supine; this procedure was performed in baseline condition and 60, 120, 180 and 240 min after the administration of bromocriptine. The protocol end points were the development of syncope or presyncope in association with hypotension with or without bradycardia. A positive response to bromocriptine test was found in 78% (95% CI, 61% to 95%) of patients and in 13% (95% CI, 0% to 26%) of controls (P<0.001). No significant differences were detectable among patients and controls showing a positive response to the test. Bromocriptine test seems to be a useful alternative tool for the diagnosis of neuromediated syncope also suggesting that dopaminergic supersensitivity may, at various and to varying degrees, play a role in the pathogenesis of syncopal episodes.

Adolescent↗

Effect of generalised sympathetic activation by cold pressor test on cerebral haemodynamics in healthy humans.

There is no general agreement regarding several aspects of the role of the sympathetic system on cerebral haemodynamics such as extent of effectiveness, operational range and site of action. This study was planned to identify the effect of a generalised sympathetic activation on the cerebral haemodynamics in healthy humans before it is masked by secondary corrections, metabolic or myogenic in nature. A total of 35 healthy volunteers aged 20-35 underwent a 5 min lasting cold pressor test (CPT) performed on their left hand. The cerebral blood flow (CBF) velocity in the middle cerebral arteries and arterial blood pressure were recorded with transcranial Doppler sonography and with a non-invasive finger-cuff method, respectively. The ratio of arterial blood pressure to mean blood velocity (ABP/Vm) and Pulsatility Index (PI) were calculated throughout each trial. CPT induced an increase in mean ABP (range 2-54 mmHg depending on the subject) and only a slight, though significant, increase in blood velocity in the middle cerebral artery (+2.4 and +4.4% on ipsi- and contralateral side, respectively). During CPT, the ratio ABP/Vm increased and PI decreased in all subjects on both sides. These changes began simultaneously with the increase in blood pressure. The increase in ABP/Vm ratio is attributed to an increase in the cerebrovascular resistance, while the concomitant reduction in PI is interpreted as due to the reduction in the compliance of the middle cerebral artery. The results suggest that generalised increases in the sympathetic discharge, causing increases in ABP, can prevent concomitant increases in CBF by acting on both small resistance and large compliant vessels. This effect is also present when a slight increase in blood pressure occurs, which suggests a moderate increase in the sympathetic discharge, i.e. when ABP remains far below the upper limit of CBF autoregulation.

Adult↗

Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications.

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.

Adult↗

Combined evaluation of pupillary and cardiovascular responses to cold pressor test in cluster headache patients.

Little is known about the structures and mechanisms involved in the pathophysiology of cluster headache (CH). In this study, pupillary and cardiovascular responses to the cold pressor test (CPT) were monitored in CH patients during either an active phase of disease or a remission period in order to evaluate the oculocephalic and cardiovascular functioning of the autonomic nervous system in this form of idiopathic headache. CH patients showed a specific pattern of pupillary response on both sides during both phases of the disease. This response differed from that of controls because of an absent miosis. The pressor response to CPT was more marked in CH patients than in controls. Naloxone pretreatment caused specific and selective changes in both the pupillary and cardiovascular responses of CH patients. These data suggest a systemic sympathetic hyperactivation in response to CPT in CH patients. An oculocephalic sympathetic hypofunction is possibly associated as well as an altered opioid neuromodulation.

Adult↗

Cerebral hemodynamics in primary headaches: the transcranial Doppler experience.

This paper is an extensive review of the use of transcranial Doppler (TCD) devices in "vascular" forms of headache, and a discussion of the possible occurrence of nonunivocal results, particularly in migraine with or without aura. Despite the large variability in findings, TCD is a noninvasive, safe, and reproducible method for studying hemodynamic phenomena which characterize the clinical profile of migraine and cluster headache attacks. Similarly, it can detect cerebrovasomotor reactivity to external/internal environmental stimuli, as well as responses to pharmacological (therapeutic or diagnostic) agents. Possible future applications of TCD in monitoring vasomotor changes in response to selective stimuli (sympathetic, neuropeptidergic, etc.) are also considered.

Cerebrovascular Circulation↗

Business management of headache centers.

Economic evaluation of the costs and benefits of a headache center or unit has become very important for headache specialists. Many of the problems concerning this "financial" approach to headache derive from the model of organization of the Headache Unit, which is dependent on the various approaches to healthcare practiced in the country considered. So far there are two models of headache center that are generally considered: the hospital-based center and the independent center. An argument favoring hospital-based headache clinics is the lower costs, primarily because of their functional connection with the services of a general hospital, i.e., neuroradiology, neurophysiology, routine laboratory analysis, etc. Another is that the headache specialist has the possibility to visit the patients presenting to the emergency room in the acute phase of headache. Independent clinics have greater costs, but are equally as effective as hospital-based models.

Ambulatory Care Facilities↗

Opposite effects of L-arginine and nitroglycerin on cerebral blood velocity: nitric oxide precursors and cerebral blood velocity.

Nitric oxide (NO), a gaseous molecule synthesized in the arteriolar endothelium from the amino acid L-arginine (L-arg), has been identified as the previously described Endothelium-Derived Relaxing Factor (EDRF): nitroderivatives such as nitroglycerin are known to induce vasodilation via NO release. The aim of this study was to evaluate by Transcranial Doppler (TCD) monitoring any changes in cerebral hemodynamics induced by both the infusion of L-arg and the sublingual administration of nitroglycerin in 20 healthy subjects. L-arg infusion induced a significant increase in blood velocity compared to the baseline value (mean +/- S.D. percent change = 18 +/- 8.71; p<0.0001 ) and a slight but significant decrease in Pulsatility Index. By contrast, nitroglycerin was able to cause a significant decrease in blood velocity (mean +/- S.D. percent change = 24.8 +/- 7.68; p<0.0001), while leaving Pulsatility Index unchanged. These data suggest that L-arg and nitroglycerin, both hypothesized to use NO as the final product at the vascular level, result in opposite blood velocity patterns within the cerebral circulation. This may be due to the particular type of artery and/or to the local endothelial environment whereby the released NO may act.

Adult↗

Haemodynamic correlates of early and delayed responses to sublingual administration of isosorbide dinitrate in migraine patients: a transcranial Doppler study.

In normal subjects or migraine patients, nitrates induce a non-specific early headache caused by vasodilation of intracranial arteries. In migraineurs a delayed headache response to nitrates may have a typical clinical profile of a spontaneous migraine attack. The cerebral vasomotor changes of this delayed response require further study. Isosorbide dinitrate (IDN), an exogenous nitric oxide (NO) donor, was given at a dose of 5 mg sublingually and a bilateral transcranial Doppler device was used to monitor bilateral mean velocity (Vm) changes at the middle cerebral artery (MCA) after IDN administration and until delayed headache occurred. Spontaneous migraine-like headache occurred only in migraine patients during the delayed phase after IDN and was accompanied by a prolonged arterial vasodilation compared to normal subjects. This vasomotor response was more evident on the customary side of the head pain of a spontaneous migraine attack. Our findings suggest a particular vasomotor response to nitrates in migraine patients. This response is associated with the nitrate-induced headache and it is not evident in healthy pain-free controls during the delayed phase after administration of an NO donor. Owing to the short half-life of NO, the neurotransmitter released by IDN, and because of the late onset of headache, we believe the mechanism is unlikely to be vascular in origin, but may have a neurogenic component.

Administration, Sublingual↗

Sympathetically-induced changes in microvascular cerebral blood flow and in the morphology of its low-frequency waves.

The effect of bilateral cervical sympathetic nerve stimulation on microvascular cerebral blood flow, recorded at various depths in the parietal lobe and in ponto-mesencephalic areas, was investigated by laser-Doppler flowmetry in normotensive rabbits. These areas were chosen as representative of the vascular beds supplied by the carotid and vertebro-basilar systems, which exhibit different degrees of sympathetic innervation, the former being richer than the latter. Sympathetic stimulation at 30 imp/s affects cerebral blood flow in 77% of the parietal lobe and in 43% of the ponto-mesencephalic tested areas. In both cases the predominant effect was a reduction in blood flow (14.7 +/- 5.1% and 4.1 +/- 2.4%, respectively). The extent of the reduction in both areas was less if the stimulation frequency was decreased. Sometimes mean cerebral blood flow showed a small and transient increase, mainly in response to low-frequency stimulation. The morphology was analysed of low-frequency spontaneous oscillations in cerebral blood flow, attributed to vasomotion. Present in 41% of the tested areas (frequency 4-12 cycles/min, peak-to-peak amplitude 10-40% of mean value), these waves decreased in amplitude and increased in frequency during sympathetic stimulation, irrespective of changes in mean flow. The possibility has been proposed that the sympathetic action on low-frequency spontaneous oscillations may contribute to the protective influence that this system is known to exert on the blood-brain barrier in hypertension.

Animals↗

Effects of cervical sympathetic nerve stimulation on the cerebral microcirculation: possible clinical implications.

The action of bilateral cervical sympathetic nerve (CSN) stimulation on mean cerebral blood flow (CBF) and on its rhythmical fluctuations was studied in normotensive rabbits by using laser-Doppler flowmetry (LDF). A reduction in mean CBF, mediated by alpha-adrenoceptors, was the predominant effect; it was more often present and larger in size in the vascular beds supplied by the carotid than in those supplied by the vertebro-basilar system. This suggests that the sympathetic action facilitates a redistribution of blood flow to the brain stem. The effect induced by CSN stimulation on CBF spontaneous oscillations was a consistent decrease in amplitude and an increase in frequency, irrespective of the changes produced on the mean level of CBF. The possible implications of the sympathetic action on the state of the blood-brain barrier (BBB) are discussed. Experimental and clinical data dealing with the influence of sympathetic activation on the cerebrovascular system have been compared. As a result the possibility of analysing the spontaneous oscillations of CBF for clinical purposes is suggested.

Animals↗

Pupillary and cardiovascular responses to the cold-pressor test.

Little is known about the structures and mechanisms involved in the autonomic response to sensory and nociceptive stimulation. In this study, we recorded simultaneously pupil diameter, blood pressure, heart rate and pain levels during a cold-pressor test in 10 healthy subjects. The aim was to evaluate the different components of the Autonomic Nervous System involved in the response to a thermal-painful stimulus. A biphasic pupillary response was observed: an initial, short-lasting mydriasis, followed by a miotic phase, this latter characterized by rhythmic fluctuations of pupil diameter. The blood pressure response was monophasic with a moderate increase observed from the second minute of the test. Pain intensities remained stable on medium-high levels throughout the test. The topical application of thymoxamine and homatropine clarified some aspects of the pupillary response. The systemic administration of naloxone suggested a role of opiates in the modulation of pupillary and cardiovascular response to the cold-pressor test.

Administration, Topical↗

Cluster headache attacks treated for up to three months with subcutaneous sumatriptan (6 mg). Sumatriptan Cluster Headache Long-term Study Group.

In the first three months of a 24-month open study to assess the safety and efficacy of subcutaneous sumatriptan 6 mg in the long-term acute treatment of cluster headache, 138 patients treated a maximum of two attacks daily each with a single 6 mg injection. A total of 6353 attacks were treated. Adverse events, reported in 28% of sumatriptan-treated attacks, were qualitatively similar to those seen in migraine long-term trials. Their incidence did not increase with frequent use of sumatriptan. There were no clinically significant treatment effects on vital signs, ECG recordings or laboratory parameters. Headache relief (a reduction from very severe, severe or moderate pain to mild or no pain) at 15 min was obtained for a median of 96% of attacks treated. There was no indication of tachyphylaxis, decrease in the speed of response, or increased frequency of attacks with long-term treatment. This study demonstrated that, in long-term use, subcutaneous sumatriptan 6 mg is a well-tolerated and effective acute treatment for cluster headache.

Adolescent↗