Transient resolution of headache in giant cell temporal arteritis after sumatriptan.
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Aged↗
Biomedical subjects
M D Ferrari
Publications and source records attributed to M D Ferrari.
Gammahydroxybutyrate and narcolepsy: a double-blind placebo-controlled study.
We treated 24 patients with narcolepsy for 4 weeks with gammahydroxybutyrate (GHB), 60 mg/kg/night, in a randomized double-blind placebo-controlled cross-over trial. Both clinical and polysomnographic criteria were used to assess the results. Compared to placebo, GHB reduced the daily number of hypnagogic hallucinations (from 0.87 to 0.28; p = 0.008), daytime sleep attacks (from 2.27 to 1.40; p = 0.001) and the severity of subjective daytime sleepiness (from 1.57 to 1.24 on a 0-4 scale; p = 0.028). The number of daily cataplexy attacks was reduced from 1.26 at baseline to 0.56 after 4 weeks of GHB intake. This reduction, however, was not statistically significantly different from the difference between baseline and placebo. GHB stabilized nocturnal rapid eye movement (REM) sleep, i.e. it reduced the percentage of wakefulness during REM sleep (p = 0.007) and the number of awakenings out of REM sleep (p = 0.016), and tended to increase slow wave sleep (p = 0.053). Adverse events were few and mild. We conclude that GHB is an effective and well-tolerated treatment for narcolepsy.
Adolescent↗
Ischemic and hemorrhagic stroke in patients on oral anticoagulants after reconstruction for chronic lower limb ischemia.
BACKGROUND AND PURPOSE: Information on the long-term fate of patients with chronic lower limb ischemia is limited. We investigated the long-term risk of the first ischemic and hemorrhagic cerebral stroke in patients on long-term anticoagulant therapy after reconstruction for chronic limb ischemia. METHODS: In a retrospective study, 376 consecutive patients were seen at regular intervals according to a standard protocol. Only 3 (0.7%) were lost during follow-up (mean duration, 5.9 years). Anticoagulation was with coumarin derivatives followed by prothrombin times periodically. Primary end points were ischemic and hemorrhagic cerebral stroke events, which were confirmed by CT scan, autopsy, or operation in 85% of the cases. Major vascular events were analyzed as a composite secondary end point. The influence of several clinical variables on these outcome events was evaluated in univariate and multivariate analyses. RESULTS: Thirty-nine patients (10%) had 41 stroke events (23 ischemic, 18 hemorrhagic); 22 of these patients (56%) died from stroke. The cumulative ischemic stroke risk was 5% at 5 years and 12% at 15 years. Prior myocardial infarction was the only independent predictor (relative risk [RR], 3.1; P < .05). The cumulative hemorrhagic stroke risk was 3% at 5 years and 17% at 15 years. Systolic hypertension (RR, 4.8; P < .01) and insulin-dependent diabetes mellitus (RR, 5.4; P < .01) were significant and independent predictors. The risk for a major vascular event was 29% at 5 years and increased to 56% at 15 years. Independent predictors were advanced age (RR, 1.4; P < .005), insulin-dependent diabetes (RR, 2.2; P < .005), and prior myocardial infarction (RR, 1.8; P < .01). CONCLUSIONS: Patients with chronic lower limb ischemia, notably those with prior myocardial infarction, are at high risk for ischemic stroke. Those with systolic hypertension or insulin-dependent diabetes mellitus are at high risk for hemorrhagic stroke.
Adult↗
Lack of asymmetry of middle cerebral artery blood velocity in unilateral migraine.
BACKGROUND AND PURPOSE: A recent transcranial Doppler study found reduced blood velocity in seven patients during migraine attacks in the middle cerebral artery at the headache side. This would implicate vasodilation of the middle cerebral artery in the pathogenesis of headache in migraine. We attempted to confirm this finding. METHODS: We determined blood velocity with transcranial Doppler ultrasonography in the middle cerebral arteries of 51 migraine patients with unilateral headache (5 with aura, 46 without aura) and of 14 patients with bilateral headache, during and outside attacks. During attacks, median time from onset of attack to transcranial Doppler examination was 6 hours (range, 1 to 35 hours). RESULTS: We found no difference between blood velocity at the headache and nonheadache sides nor between blood velocity during and outside attacks. Similar results were obtained in a subgroup of 11 patients who were investigated in the first 4 hours of an attack. There were also no differences between attacks with unilateral or bilateral headache. CONCLUSIONS: We cannot support the hypothesis that migraine is associated with vasodilation of the middle cerebral artery ipsilateral to the headache.
Adolescent↗
Sumatriptan in the treatment of migraine.
The headache phase of the migraine attack is thought to be associated with a dilation of cranial blood vessels, particularly those in the dura mater, and an accompanying localized sterile inflammatory response. Serotonin, or 5-hydroxytryptamine (5-HT), is considered a possible mediator of this syndrome. Receptors for 5-hydroxytryptamine are present in cranial arteries and are widely distributed in the CNS. Studies indicate that sumatriptan, a 5-HT1 receptor agonist, is effective in treating acute migraine attacks. The mechanism of sumatriptan's therapeutic action is not completely understood. Evidence from animal and human studies suggests that sumatriptan constricts dural vessels and inhibits neuropeptide release from trigeminal nerve endings by activating 5-HT1 receptors. Clinically, sumatriptan is rapidly effective against all features of the headache phase in migraine in up to 80% of patients. The headache may recur, however, within 24 hours in about one third of patients, but this can be treated effectively with a subsequent dose of sumatriptan. Treatment with sumatriptan has been well tolerated with only minor, transient, acute side effects reported. At present, only limited information is available regarding long-term tolerability, safety, and efficacy. Sumatriptan should not be prescribed to patients with a cardiovascular history.
Humans↗
Effects of tertatolol, a beta-adrenoceptor antagonist with agonist affinity at 5-HT1A receptors, in an animal model of migraine: comparison with propranolol and pindolol.
Constriction of carotid arteriovenous anastomoses is a common property of several antimigraine drugs. The present study concerns the effects of tertatolol (0.1, 0.3, 1 and 3 mg/kg i.v.), a novel beta-adrenoceptor antagonist with an agonist action on 5-HT1A receptors, on systemic haemodynamics and carotid blood flow distribution in the anaesthetized pig. Two other beta-adrenoceptor antagonists, one (propranolol) with and one (pindolol) without antimigraine actions, were compared (doses: 0.03, 0.1, 0.3 and 1 mg/kg i.v.) with tertatolol in this animal experimental model of migraine. While the beta-adrenoceptor antagonist with partial agonist action, pindolol, increased heart rate and cardiac output, propranolol and tertatolol decreased these variables moderately. Mean arterial blood pressure also decreased with the two highest doses of propranolol and with the highest dose of tertatolol. The calculated total peripheral conductance decreased with the first three doses of tertatolol. Carotid haemodynamic variables were not affected by pindolol, except for some increase in the nutrient fraction after the highest dose. Propranolol and especially tertatolol decreased both total carotid blood flow and arteriovenous anastomotic blood flow without affecting the nutrient fraction. In the case of tertatolol, blood flow decreases were accompanied by similar decreases in vascular conductance, indicating active arteriovenous anastomotic constriction. It is therefore suggested that tertatolol may prove effective in the treatment of migraine.
Adrenergic beta-Antagonists↗
Clinical effects and mechanism of action of sumatriptan in migraine.
Sumatriptan is a novel, highly effective drug against migraine and cluster headache attacks. It shows a remarkably selective pharmacological profile in animals. Determination of its mechanism of action in human should further the understanding of the pathophysiology of migraine and cluster headache. We, therefore, review current knowledge on the clinical and pharmacological effects of sumatriptan. Important pharmacological actions of sumatriptan are (i) poor penetration of the blood-brain barrier suggesting a peripheral point of action; (ii) 5-HT1-like/5-HT1d receptor-mediated vasoconstriction of large cerebral arteries and dural vessels; and (iii) blockade of neurogenic dural inflammation via 5-HT1d autoreceptor-mediated inhibition of vasoactive neuropeptides within the trigeminovascular system. Future research will tell which mechanism is involved in the pathophysiology of migraine and cluster headache.
Animals↗
Blood flow velocities in the vertebrobasilar system during migraine attacks--a transcranial Doppler study.
In this study, blood flow velocity in the basilar artery and both vertebral and middle cerebral arteries was measured with a transcranial Doppler device in 23 migraineurs during and outside a migraine attack. The aim of the study was to compare blood flow velocities during and outside an attack and to examine vascular reactivity to voluntary hyperventilation during both conditions. No differences in blood flow velocity were found. Although blood pressure was increased and end-expiratory CO2 decreased during the attack, this exerted no influence on blood flow velocity. Neither was a difference in vascular reactivity to voluntary hyperventilation detected between the two conditions. These findings support the notion of functional integrity of the examined large arteries during migraine attacks without aura.
Adult↗
From serotonin receptor classification to the antimigraine drug sumatriptan.
After the synthetic serotonin 5-hydroxytryptamine (5-HT) became available in the early 1950s, attempts were soon under way to study the nature of 5-HT receptors. Using the guinea-pig isolated ileum, Gaddum and Picarelli (1957) suggested that 5-HT-induced contractions were mediated by a morphine-sensitive "M" receptor located on the parasympathetic ganglion and a dibenzyline-sensitive "D" receptor located on the smooth muscle. Though this classification ws used during the next three decades, it was realized that some effects of serotonin, for example vasoconstriction within the carotid vascular bed, were not mediated by either "M" or "D" receptors. When radioligand binding studies led to the identification of 5-HT1 and 5-HT2 "receptors" in the rat brain membranes, it became increasingly apparent that the two receptor classifications were not identical. Thus, a new framework for serotonin receptor nomenclature and classification was proposed: 5-HT1-like (5-HT1), 5-HT2 (formerly "D") and 5-HT3 (formerly "M") receptors. At the present time, several subtypes of 5-HT1 receptors as well as a 5-HT4 receptor are also recognized. As the serotonin receptor classification was emerging to indicate that carotid vasoconstriction by serotonin is mediated by a subtype of 5-HT1 receptors, on the migraine front it was being suggested that the disease is associated with vasodilation within the cranial extracerebral circulation and deranged serotonin metabolism and that certain antimigraine drugs caused a selective carotid vasoconstriction, probably via serotonin receptors. Therefore, Humphrey and colleagues conceived that synthesis of serotonin derivatives may lead to a compound that would elicit highly selective carotid vasoconstriction and abort migraine attacks. Indeed, via the synthesis of 5-carboxamidotryptamine and AH25086, sumatriptan was designed. The drug acts as an agonist at the vasoconstrictor 5-HT1 receptor subtype and has proved highly effective in the therapy of migraine attacks.
Animals↗
Treatment of migraine attacks with subcutaneous sumatriptan: first placebo-controlled study. The Subcutaneous Sumatriptan International Study Group.
The results of the very first large-scale placebo-controlled dose-response trial with the novel selective 5-hydroxytryptamine1-like (5HT1-like) receptor agonist sumatriptan are presented. We studied the efficacy and tolerability of subcutaneous injections of 1 mg, 2 mg and 3 mg of sumatriptan in alleviating migraine attacks in a double-blind, placebo-controlled, parallel-group, multicentre clinical trial. Six-hundred and ninety patients were randomized and 685 received study medication. At 30 min, reduction of headache severity to mild or none (primary efficacy endpoint) was achieved in 22% (95% CI: 15-28%) of placebo-treated patients and in 39% (CI: 31-46%) of patients treated with 1 mg sumatriptan, 44% (CI: 36-51%) treated with 2 mg sumatriptan and 55% (CI: 48-63%) treated with 3 mg sumatriptan. Differences from placebo were 17% (CI: 8-27%) for 1 mg sumatriptan, 22% (CI: 13-32%) for 2 mg sumatriptan and 34% (CI: 24-44%) for 3 mg sumatriptan (p < 0.001 for all three comparisons). Other migraine symptoms were also more effectively treated by sumatriptan than by placebo. Subsequently, an open-label 3 mg dose subcutaneous sumatriptan was given to partial or non-responders. Thirty minutes after this open dose the response rate to sumatriptan had improved to between 70 and 80%. Adverse events after sumatriptan were minor and short-lived. We conclude that subcutaneous sumatriptan is well tolerated in doses up to 3 + 3 mg and may rapidly abort migraine attacks.
Adolescent↗
The pharmacology of antimigrainous drugs.
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Humans↗
Antimigraine drug sumatriptan increases blood flow velocity in large cerebral arteries during migraine attacks.
Sumatriptan, a novel selective 5-hydroxytryptamine1d (5-HT1d) receptor agonist, which is highly effective in the acute treatment of migraine attacks, blocks dural neurogenic plasma extravasation and constricts cranial blood vessels in animal experiments. We measured intra- and extracranial blood flow velocities (BFV) with a transcranial Doppler device in 67 patients during a spontaneous migraine attack, before and after treatment with 3 mg or 6 mg subcutaneous sumatriptan or placebo. Sumatriptan, but not placebo, significantly increased BFV (cm/sec) in the internal carotid and middle cerebral arteries on both sides, without detectably changing the BFV in the common and external carotid arteries. The rise in BFV increased with the dose of sumatriptan, parallel to an increase in proportion of patients improved. There were no significant changes in heart rate, blood pressure, or respiratory frequency after treatment with sumatriptan. The increase in BFV probably reflects vasoconstriction of the large basal intracranial arteries, which may be a mechanism for the antimigraine action of sumatriptan.
Adolescent↗
Biochemistry of migraine.
The biochemistry of migraine is complex. Many contradictory or never replicated findings in often small patient groups have been published. The following observations in the platelet-free plasma and urine appear to have some solid basis and will be discussed: 1) systemic derangement of 5-HT metabolism, relevant to the peripheral vascular component of migraine pathophysiology, 2) changes in neuroexcitatory amino acids and magnesium, which may reflect a predisposition of the migraine patient, notably those having attacks with aura, to develop spreading depression, 3) alterations in methionine-enkephalin levels, which may be a useful marker to discriminate between tension headache and migraine, 4) hormonal fluctuations which seem important to set the threshold for an attack, 5) changes of vasoactive peptides in the cranio-vascular circulation, providing the first human evidence that the trigemino-vascular system indeed is relevant in migraine, and 6) catecholaminergic changes suggesting sympathetic overactivity. Finally distinct biochemical differences between patients with migraine without aura and patients with tension headache on one hand, and between patients with migraine with aura and patients with migraine without aura on the other hand will be emphasized. Findings in platelets will be discussed only if they are complementary and supportive to the plasma and urine data.
Aspartic Acid↗
Effect of aeration rate on the alcoholic fermentation of whey by Kluyveromyces fragilis.
In this paper, the influence of aeration rate on the alcoholic batch fermentation of whey by Kluyveromyces fragilis NRRL Y-2415 was investigated. Assays in 1.5-L fermentor using concentrated whey permeate containing 100 g/L of lactose were carried out at different oxygen supply rate (KLaC*) from 0 to 82 mmol/Lh. Optimum response was obtained at 14 mmol/Lh: ethanol production rate reached was 3.4 g/Lh yielding 0.46 g of product per gram of initial lactose. An increase of KLaC* from 0 to 14 mmol/Lh improved the ethanol production: maximum specific ethanol production rate (qpm) increased 3.3 times from 0.3 to 1.0 g/gh. For higher aeration levels, ethanol production diminished and biomass formation was stimulated. The declination of qpm and the increase of microns at higher aeration level lead to conclude the importance of a controlled oxygen supply in order to obtain the required balance between yeast biosynthetic needs and ethanol production.
Animals↗
[Sumatriptan in migraine and cluster headache].
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Cluster Headache↗
['Only ergotamine still helps'].
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Adult↗
No confirmation of visual evoked potential diagnostic test for migraine.
We have attempted to replicate the results of studies on a diagnostic test reported to have 90% sensitivity and 89-96% specificity for migraine. The technique is based on peak-to-peak measurements of fast background electroencephalographic activity during a visual evoked potential (VEP) study. VEP latencies and amplitudes did not differ significantly, and showed substantial overlap, between a group of eight migraine patients and ten age-matched healthy controls. We could not recognise previously described fast activity or measure it objectively by peak-to-peak measurements. We cannot confirm that measurement of fast wave activity in the VEP background is useful in diagnosis of migraine.
Adult↗
5-HT3 receptor antagonists and migraine therapy.
Neuronal 5-hydroxytryptamine3 (5-HT3) receptors mediate the excitatory effects of 5-HT. They are located in pain- and nausea-modulating areas in the central nervous system and on C-fibre primary afferents in the peripheral nervous system. Consequently, these receptors mediate the painful and emetic effects of 5-HT. Selective and potent 5-HT3 receptor antagonists have been shown to block inflammatory and 5-HT induced and potentiated "vascular pain". Based on the hypothesis that 5-HT3 receptor antagonists may block neurogenic dural inflammation in the distribution area of the trigeminal nerve and, thus, could potentially prevent migraine (pain), four highly selective and potent 5-HT3 receptor antagonists have been tested in both the acute and prophylactic treatment of migraine. Unfortunately, except for a clear anti-emetic effect, none of these drugs has shown unequivocal efficacy in the treatment of migraine. This may be partly due to the complex (bell-shaped) dose-response relationship of these compounds, making exact titration of the correct dose difficult. Moreover, most 5-HT3 receptor antagonists have proved to be toxic in man on chronic administration thereby preventing further trials in migraine with adjusted doses. Short-term treatment for cytotoxic drug-induced emesis so far appears to be the only proven indication for 5-HT3 receptor antagonists.
Humans↗