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Biomedical subjects

G Micieli

Publications and source records attributed to G Micieli.

At least 19 recordsLinked to original sources

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

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

Increased cerebral blood flow velocity induced by cold pressor test in migraine: a possible basis for pathogenesis?

Noradrenergic nuclei of the locus coeruleus are believed to be involved in migraine pathogenesis. We recently demonstrated a typical intracerebral vasoconstriction after prolonged (5 min) exposure to cold pressor test (CPT), likely related to a central noradrenergic mechanism modulated at the locus coeruleus level and eliminated by pretreatment with clonidine. In the present study, we used transcranial Doppler ultrasonography to monitor blood flow velocity (BFV) changes to CPT in the middle cerebral artery (MCA) of migraine with (MA, n = 12) and without (MO, n = 15) aura subjects. CPT induced a significant increase in BFV and a concomitant decrease in the pulsatility index (PI), a pattern which is the opposite of the results obtained with controls. The results were comparable when controls were pretreated with clonidine. The MO patients produced an intermediate pattern between the MA and control subjects. A possible altered modulatory effect of opioids and/or serotonin on noradrenergic nuclei of the brainstem is the possible cause of the observed inverse response in migraine, suggesting intracerebral vasomotor instability in these patients.

Adult

Headache and quality of life.

The present prospective-type study quantified, by way of and ad hoc questionnaire, the impact of the headache attack in its various manifestations and the effect of headache on the quality of life of 400 headache sufferers. In addition, the functional status of episodic headache patients has been compared to that of patients with chronic daily headache. We observed that during headache attacks, episodic headache patients were significantly more disabled by physical symptoms. On the contrary, patients with chronic daily headache showed a significantly greater occurrence of emotional disturbances. A difference was detectable for mental health which was significantly more compromised in chronic daily headache than in episodic headache patients (P < 0.05). During the interictal period, quality of life appeared more compromised in chronic daily headache than in episodic headache patients. Chronic daily headache subjects were characterized by higher disability scores in all the sections considered. The results of this investigation confirm that headache negatively influence a patient's quality of life not only during attack phases but also during interictal periods and underline the importance that future studies on the efficacy of headache treatments should also evaluate the impact on patient's quality of life.

Adolescent

Quantification of headache disability: a diagnostic-based approach.

The quantification of the social and economic handicaps caused by headache is a complex problem, especially given the great variability of headache patients' clinical pictures. In the present study, 400 patients, consecutively admitted to Headache Centers in Pavia and Milan, were interviewed on the relationship between headache and their work and social activities, in order to evaluate their socioeconomic handicap due to headache. The analysis of the data primarily focused on attack-type headaches (migraine, cluster headache, and episodic tension-type headache) and chronic or daily headaches (chronic tension-type headache and migraine combined with tension-type headache). These latter types were often characterized by the daily use or abuse of analgesics. The overall profile which emerged from the study reveals relatively low levels of handicap or disability in work and social activities. These low levels can be mainly attributed to timely, and at times excessive, use of analgesics.

Absenteeism

Sleep-apnoea and autonomic dysfunction: a cardiopressor and pupillometric study.

Isolated alterations in the autonomic nervous system (ANS) have been described in obstructive sleep-apnea syndrome (OSAS), but the exact nature and degree of ANS involvement in OSAS is as yet uncharted. In the present study we evaluated some autonomic nervous functions in 13 OSAS patients using cardiopressor and pupillometric tests. Almost all showed only slight alterations of ANS function, generally in the form of a hypofunction of both sympathetic and parasympathetic branches. Pupillometry was more sensitive than cardiovascular indexes in detecting neurovegetative involvement which correlated with some respiratory indices. The data suggest that autonomic involvement in OSAS is ascribable to metabolic changes (hypoxia, hypercapnia) rather than to primary "neurogenic" alterations.

Adult