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Biomedical subjects

G Nappi

Publications and source records attributed to G Nappi.

At least 145 records · Page 8Linked to original sources

Effects of terguride on anterior pituitary function in parkinsonian patients treated with L-dopa: a double-blind study versus placebo.

In a randomized double-blind study, 20 parkinsonian patients (suffering from the disease for 2-18 years), chronically treated with levodopa (500-750 mg/day for 0.5-12 years), received terguride (1 mg b.i.d.) or placebo for 4 weeks. Growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and insulin-like growth factor (IGF-I) secretions were studied before and after the morning dose of levodopa (250 mg p.o.), both before and at the end of study period. At the beginning of the study, basal hormonal levels were within normal limits, and levodopa administration induced a significant suppression in PRL and TSH levels (both p < 0.01)) and a significant increase in GH (p < 0.01). The same results were observed at the end of the study period in the placebo group. Addition of terguride induced a significant suppression in basal PRL levels (p < 0.01), whereas levodopa-induced hormonal changes were unaffected. These data suggest that the hypothalamic dopaminergic function that controls anterior pituitary hormones is preserved in parkinsonian patients, regardless of both the duration of the disease and the long-term treatment with levodopa. The strong additional prolactin-lowering effect of terguride indicates long-lasting dopaminergic effects, as is already known from hyperprolactinemic conditions. The dopaminergic effects of levodopa on TSH, GH, and IGF-I secretion were unchanged by terguride treatment. The anti-dopaminergic effects of terguride observed in the motor system in animal studies, as well as in levodopa-induced dyskinesias in parkinsonian patients, could not be observed in the case of the dopaminergic control of anterior pituitary hormones under the conditions of this study.

Aged↗

Posatirelin in the treatment of vascular dementia: a double-blind multicentre study vs placebo.

INTRODUCTION: The usefulness of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having modulatory activity on the monoaminergic and cholinergic systems and neurotrophic effects, was evaluated in vascular dementia. PATIENTS AND METHODS: A multicentre, parallel groups, double-blind clinical study vs placebo was carried out with patients suffering from probable vascular dementia according to the NINDS-AIREN criteria. The study consisted of a two-week run-in of a once daily, orally administered, placebo phase, followed by 12 weeks of intramuscular treatment with posatirelin 10 mg/ml or placebo given once a day and a follow-up after one month's withdrawal. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale for dementia, the Randt Memory Test and the Toulouse-Piéron Attention Test. Data were evaluated using analysis of variance and covariance. RESULTS: As regards GBS scores, patients treated with posatirelin showed a significant improvement in intellectual performance, in orientation, motivation and memory as compared to controls. The improvement of memory performance was also confirmed by the acquisition score and memory index of the Randt Memory Test. At the end of the follow-up period the differences between treatments were still maintained. Tolerability was good. CONCLUSIONS: The significant improvement observed in cognitive functions, attention and motivation of demented patients treated with posatirelin suggests the potential usefulness of this drug in vascular dementia. Furthermore, the presence of a long-lasting effect after drug withdrawal suggests the possibility of administering the drug cyclically.

Aged↗

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↗

Combined response of plasma and platelet catecholamines to different types of short-term stress.

Platelet catecholamines (CAs) do not seem to reflect the acute increases in plasma CAs observed during stress, at least over short periods of time. However, it is well known that stress, via the release of plasma CAs, is capable of affecting platelet function. To better address this issue, we studied platelet and plasma levels of free noradrenaline (NA), adrenaline (A), and dopamine (DA) in 10 healthy subjects undergoing three different stress tests: insulin tolerance test (ITT), cold pressor test (CPT) and handgrip test (HT). We also evaluated platelet count and platelet mean volume (MPV). ITT caused a considerable increase in plasma NA and a massive release of plasma A, while CPT and HT induced discrete increases only in plasma NA. ITT induced a significant decrease in platelet DA and a trend toward a decrease in platelet NA, along with a significant increase in MPV. All these changes occurred in coincidence with the peak levels of plasma CAs. No changes in platelet variables were observed in response to both CPT and HT. The modifications observed during ITT are likely to represent signs of an initial platelet activation in response to the acute plasma CA elevations this test was able to elicit. Our data show that platelet CA content does not represent a mere reflection of the circulating concentrations of plasma CAs, but it is the result of a dynamic balance between these two compartments.

Adult↗

"Off" painful dystonia in Parkinson's disease treated with botulinum toxin.

The "off" painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during "on" periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s.c. infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are alos used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3-7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated "on" foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well-known underlying dopaminergic defect in OPD, the Btx therapy should be considered only if the dopaminergic treatment established for the management of OPD has failed.

Aged↗

Classification of chronic daily headache by International Headache Society criteria: limits and new proposals.

We conducted a retrospective study of 150 patients with chronic daily headache (CDH) to determine how to categorize their headache according to the classification of the International Headache Society (IHS). All patients were first evaluated at Parma and Pavia Headache Centres (from January 1992 to March 1993) and had had headache for at least 15 days a month during the previous 6 months. Four patients were thereafter excluded due to poor reliability. The 146 patients who met our CDH criteria (92 with and 54 without clear-cut migraine attacks) could be classified into four groups: (i) chronic tension-type headache (CTTH)--27 patients; (ii) coexisting migraine plus CTTH--65 patients; (iii) unclassifiable daily headache--27 patients; and (iv) migraine and an unclassifiable interval headache--27 patients. Seventy-two percent of patients with CDH had migraine as the initial form of their headache. We therefore propose to revise the IHS classification for migraine, taking into account its evolution, and add two subcategories, migraine with interparoxysmal headache and chronic migraine.

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↗

Autonomic disorders in Parkinson's disease.

Patients with idiopathic Parkinson's disease (IPD) often show signs and symptoms of autonomic involvement, related to the disease itself or to its progression. The more frequently disturbances reported are connected with loss of extrapyramidal motor control, i.e. dysphagia, gastric emptying and the most common constipation. They concern about 73% of the patients. A high frequency of urinary symptoms, ranging from 37% to 71%, is also reported in IPD, in particular detrusor hyperreflexia causing urgency, frequency of micturing or urgency incontinence. Another autonomic groups of symptoms are related to the failure of cardiopressor adaptability which involve 15% of the subjects and are more typical of late onset cases or forms bordering with the Multiple System Atrophy, finally resulting in orthostatic hypotension (OH).

Autonomic Nervous System Diseases↗

[Therapeutic guidelines for headache].

Guidelines have been recently introduced in clinical practice in order to improve the quality of patient care reducing health-care costs. In 1993 the Italian Headache Society has published the "Guidelines and recommendation for the treatment of migraine" based on a wide revision of the existing literature and a consensus conference of Italian headache experts. These guidelines include the information necessary to make a correct diagnosis and to identify the best symptomatic and/or prophylactic migraine treatment. Until now guidelines for the treatment of tension-type headache and cluster headache are not available. However we can refer to the "Treatment recommendations" proposed by the Educational Committee of the International Headache Society. These suggestions indicate common practice and give precise information about types and dosages of the drugs utilizable for the prophylaxis and for the treatment of attacks.

Cluster Headache↗

Oral sumatriptan compared with placebo in the acute treatment of migraine.

This multicentre, double-blind, parallel-group study compared the efficacy, safety and tolerability of oral sumatriptan, given as a new film-coated tablet, with placebo in the acute treatment of migraine. Patients were randomised unequally (1:2) to receive placebo or sumatriptan. Eighty-eight patients received placebo (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h) and 162 patients received sumatriptan 100 mg (plus an optional 100 mg dose at 2 h and an optional 100 mg dose within 24 h). Sumatriptan was significantly more effective than placebo at relieving headache (defined as reduction in severity from severe or moderate pain to mild or no pain) at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). More sumatriptan-treated patients were completely pain free compared with placebo-treated patients at both 2 h (24% versus 12%) and 4 h (48% versus 18). Patients receiving sumatriptan reported earlier onset of headache relief than patients receiving placebo. Headache relief in sumatriptan-treated patients was similar, irrespective of the type of migraine (with or without aura) or the time of treatment < or = 4 h or > 4 h after onset of migraine). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

International Headache Society classification: interobserver reliability in the diagnosis of primary headaches.

We assessed interobserver reliability of the International Headache Society (IHS) classification for diagnosis of primary headaches. The study was performed on 103 patients consecutively seen at two Headache Centres. Each patient was given a structured interview recorded on videotape. Four experienced clinicians then reviewed the interviews separately and made a diagnosis of headache according to IHS criteria at the one- and two-digit levels. At both the one- and the two-digit level the agreement was substantial (Kappa = 0.74 and 0.65, respectively). The analysis of reliability for each of nine items necessary for diagnosis showed an agreement ranging from substantial (Kappa = 0.69) to almost perfect (Kappa = 0.89). Our results indicate that the IHS classification has a good reliability for the diagnosis of primary headaches at the one- and two-digit levels.

Adolescent↗

Oral sumatriptan: effect of a second dose, and incidence and treatment of headache recurrences.

Oral sumatriptan in a dose of 100 mg aborts about 60% of migraine attacks within 2 h, but the headache may recur within 24 h. We investigated: (i) the incidence of headache recurrence after oral sumatriptan (ii) whether a second tablet of sumatriptan at 2 h increases initial efficacy and/or (iii) prevents headache recurrence and (iv) whether a further tablet of sumatriptan treats headache recurrence. In a randomized parallel-group clinical trial, 1246 patients treated one to three migraine attacks (with or without aura), with 100 mg oral sumatriptan. Two hours later they all took a double-blind randomized second table of sumatriptan (group I) or placebo (group II). Patients who initially improved, but then experienced headache recurrence took a further double-blind randomized tablet of sumatriptan or placebo. Proportions of patients who improved from moderate/severe headache to mild/none were similar in groups I and III at 2 h (55 vs 56%) and 4 h (80 vs 77%). Incidences of headache recurrence (moderate/severe-any grade of headache) and median times to headache recurrence were also similar: 22-32% at 16 h in group I and 25-33% at 16.5 h in group II. Sumatriptan was superior to placebo in treating headache recurrence: 74 vs 49% (p = 0.017) in group I and 70 vs 30% (p = 0.0001) in group II. Thus, one-fourth of patients experience headache recurrence at about 16 h after successful treatment of a migraine attack with 100 mg oral sumatriptan. A second tablet of sumatriptan at 2 h does not increase initial efficacy and neither prevents nor delays headache recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Bilateral asymmetry of cerebral blood velocity in cluster headache.

In this study, 69 episodic cluster headache (CH) patients (40 in the active phase, 29 in remission period) underwent a complete TCD examination in order to verify the relationship between cerebral blood velocities (CBVs) and the clinical profile of the disease. Fifteen patients were examined during both phases, while 7 were monitored during a spontaneous attack. Sixty-three healthy sex and age-matched controls were also studied. We measured widespread, asymmetric CBV activation during the active phase, bilaterally in the anterior circulation and also in the posterior circulation. A relative reduction of CBV on the anterior cerebral artery pain side, also during remission, suggests a relationship between local vasodilation and the autonomic symptoms ipsilateral to pain during CH attacks.

Adult↗

Comparative study with EMG, pressure algometry and manual palpation in tension-type headache and migraine.

According to International Headache Society classification criteria, the presence of pericranial muscle disorder in tension-type headache should be evaluated using one of the following methods: EMG, pressure algometry or manual palpation. The purpose of this study was to compare the results of these three methods in 15 patients with episodic tension-type headache, 29 with chronic tension-type headache and 22 presenting migraine without aura compared to those obtained in healthy individuals. Algometric and EMG recordings at the frontalis muscle during mental arithmetic were more impaired in episodic and chronic tension headache patients than in controls and migraine patients. Chronic tension headache patients were significantly impaired at the trapezius muscle in all three tests compared to controls. Our data indicate that when two or three tests were carried out the diagnostic capacity was significantly improved in comparison to only one test. Moreover, since a different pattern could be seen with pain and without pain, the existence of headache at the time of testing should be taken into consideration.

Adolescent↗