A new vitamin K epoxide reductase complex subunit-1 (VKORC1) mutation in a patient with decreased stability of CYP2C9 enzyme.
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Adult↗
Biomedical subjects
G D'Andrea
Publications and source records attributed to G D'Andrea.
Treatment of aura: solving the puzzle.
Migraine with aura (MwA) sufferers, at times, need specific treatments. This is the case when the auras are frequent, prolonged and cause anxiety and distress. Abnormal release of glutamate, which may trigger auras, and abnormal platelet behaviour, which constitutes a possible predisposing factor to MwA, are possible targets for MwA-specific prophylactic therapy. Here we present results obtained using lamotrigine (two open trials), an agent known to inhibit glutamate release, and picotamide, an antiplatelet drug, in the prophylactic treatment of MwA sufferers. Lamotrigine significantly reduced the frequency of MwA attacks, and picotamide together with lamotrigine reduced the duration and/or the occurrence of auras. In comparison to lamotrigine, the therapy with picotamide may have some advantages such as the use of the therapeutic dose from the first day of treatment (lamotrigine needs one month or more to reach such a dose) and the possibility to prevent cerebral ischaemic events and migraine stroke, a rare but severe complication of MwA attacks.
Anticonvulsants↗
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↗
The effect of AZT and chloroquine on the activities of ricin and a saporin-transferrin chimeric toxin.
This study deals with the combination of chloroquine (CQ, an anti-malaric drug) and 3'-azido-3'-deoxythymidine (AZT, anti-human immuno-deficiency virus (HIV) drug) with a chimeric toxin (TS) obtained by chemical linking of saporin (a ribosome inactivating protein from the plant Saponaria officinalis) and human transferrin, in the intoxication of the human chronic myeloid leukaemia cells (K562). Our data demonstrate that AZT, at concentrations comparable to those reached in the blood of HIV-infected patients under pharmacological treatment with this drug, can increase the toxicity of TS in cooperation with CQ inducing an increased effect on protein synthesis in K562 cells ( approximately 50% inhibition of protein synthesis for TS alone, and TS with AZT and approximately 70% with both AZT and CQ). Furthermore, pre-treatment of cells with AZT alone can induce an increase of apoptosis in K562 cells intoxicated with TS. By comparing data obtained with the model toxin ricin, we get indications that the two toxins partially differ in their intracellular routes, also suggesting that chimeric constructs containing ricin-like toxins (i.e. immunotoxins) could be coupled with the use of common and cheap drugs for the treatment of cancer in HIV-infected patients.
Apoptosis↗
Migraine with aura from pathophysiology to treatment: therapeutic strategies.
Migraine with aura (MwA) sufferers, at times, need specific treatments. This is the case when the auras are frequent, prolonged and cause anxiety and distress. Abnormal release of glutamate, that may trigger auras, and abnormal platelet behaviour, that constitute a possible predisposing factor to MwA, may be possible targets for MwA specific prophylactic therapy. Here we present results obtained by using lamotrigine, an agent known to inhibit glutamate release, and picotamide, an antiplatelet drug. Both drugs significantly reduced, in two open label trials, the frequency and the duration of auras. In comparison with lamotrigine, the therapy with picotamide may offer some advantages, such as the use of the therapeutical dose from the first day of treatment (lamotrigine needs one month to reach such a dose) and the possibility to prevent cerebral ischaemic events and migraine stroke, a rare but severe complication of MwA attacks.
Epilepsy↗
High-dose radiation-induced meningioma in children - case report and critical review of the literature.
OBJECT: High-dose radiation-induced meningiomas in children are a rare occurrence. We discuss the clinical data and the differences of these rare tumors from those of spontaneous counterpart and radiation-induced meningiomas of the adult population. CASE REPORT: We report a case of meningothelial meningioma, which occurred in a 9-year-old boy who underwent radiotherapy for a parieto-occipital cutaneous angioma. In addition, we collected 18 cases of high-dose radiation-induced meningiomas in children from a literature review with Medline. RESULTS: Radiation-induced meningiomas in children show a female predominance, a short latency period that seems to be related to the age at irradiation, and an aggressive behaviour. CONCLUSION: Exposure to the potentially carcinogenic effects of radiotherapy should be reserved only for tumors that demonstrate subsequent progression. A meticulous follow-up of patients treated with radiation therapy is mandatory.
Child↗
Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature.
Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.
Aged↗
Elevated levels of circulating trace amines in primary headaches.
BACKGROUND: Trace amines, including tyramine, octopamine, and synephrine, are closely related to classic biogenic amines. They have been hypothesized to promote migraines and other types of primary headaches, but there is no direct evidence supporting this hypothesis. METHODS: Using a multichannel electrochemical high-performance liquid chromatography system, the authors evaluated whether changes in circulating trace amines occur in subjects with migraine (with or without aura) during headache-free periods as well as in patients with cluster headache (CH) during the remission and active phases as compared with healthy control subjects. RESULTS: Plasma levels of all trace amines were significantly higher in CH patients, in both the remission and the active phases, when compared with control subjects or subjects with migraine. In addition, intraplatelet levels of octopamine, synephrine, and tyramine were higher in CH patients than in control subjects. In migraine patients, plasma levels of octopamine and synephrine were higher compared with controls, although in migraine with aura, the difference was not significant. CONCLUSIONS: Whereas the elevation of plasma trace amine levels in both migraine and CH supports the hypothesis that disorders of biogenic amine metabolism may be a characteristic biochemical trait in primary headache sufferers, the observation that such alterations are more prominent in patients with CH than migraine patients suggests that they may reflect sympathetic or hypothalamic dysfunction.
Adolescent↗
Contributions of biochemistry to the pathogenesis of primary headaches.
We briefly summarise biochemical anomalies of serotonin, norepinephrine, glutamic and aspartic acids, the main neurotransmitters of inhibitory and excitatory neuronal circuitries, found in primary headaches and their relationship with pathogenesis of migraine and cluster headache (CH). In addition, the high levels of circulating tyramine, octopamine and synephrine (elusive amines), recently reported in both migraine types and CH, are discussed in relation to the other "classic" amines findings. In particular it is suggested how abnormal levels of elusive amines may participate in the pathophysiology of migraine and CH acting through their specific trace amine receptors and alpha and beta receptors. The possible hypothesis that emerges from the analysis of these biochemical findings is that an imbalance of systems, with opposite neurophysiological functions related to the pain and other yet unknown functions, may constitute the biochemical phenotype of migraine with and without aura, and CH.
Brain Chemistry↗
Strategies for the treatment of autonomic trigeminal cephalalgias.
Trigeminal autonomic cephalalgias (TACs) are a group of primary headache syndromes characterised by two main clinical characteristics: pain and oculofacial autonomic phenomena. Three headache forms are grouped as TACs: cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). These are distinguished mainly on the basis of attack duration. It lasts from 15 to 180 min in CH, from 2 to 30 min in PH and from 5 to 240 s in SUNCT. The most effective drug preventative in PH is indomethacin even if in few cases other non-steroidal anti-inflammatory drugs have been reported to be effective. SUNCT is commonly described as drug resistant. Recent studies report that lamotrigin may be the drug of choice for SUNCT.
Adrenal Cortex Hormones↗
Picotamide in migraine aura prevention: a pilot study.
In an open, preliminary trial we evaluated the use of picotamide, an antiplatelet drug, in the prophylactic treatment of migraine aura (MA). Twenty-two women suffering from migraine with typical aura or MA without headache, diagnosed according to International Headache Society criteria, entered a nine-month study. They underwent a three-month run-in period free of prophylactic drugs, followed by a six-month treatment period (subdivided in two trimesters, TI and TII) with 300 mg of picotamide administered twice daily. A detailed diary reporting neurological symptoms, duration and frequency of MA was compiled by patients along the trial time. The number of MA significantly decreased during treatment (from 6.85+/-3.82 in the run-in trimester to 2.85+/-2.72 during TI and to 2.55+/-2.89 during TII). Also, MA duration was decreased significantly, being 36.75+/-20.28 min during run-in, 20.00+/-16.94 during TI and 17.75+/-16.26 during TII. In 25% of patients MA totally disappeared. The number and the features of aura neurological symptoms were also positively modified by the use of picotamide. No serious adverse event was provoked by picotamide administration. Picotamide is effective in reducing MA frequency, duration and symptomatology. The effect is clearly evident in the first trimester of treatment and is maintained with no further modifications during the second trimester.
Adolescent↗
Elusive amines and cluster headache: mutational analysis of trace amine receptor cluster on chromosome 6q23.
Cluster headache (CH) is characterised by unilateral pain and ipsilateral autonomic features. To date, no molecular genetic evidence has been shown for CH. Small pedigrees and low penetrance render the identification of the CH-gene quite difficult. Nonetheless the association of CH and migraine to a new class of amine, namely trace or elusive amines such as tyramine, octopamine and synephrine, has recently been demonstrated. In particular, in comparison to healthy control subjects, all these neurotransmitters have been found to be greatly elevated in CH sufferers in plasma and platelets both in active and remission periods. A cluster of gene-encoding G-protein-coupled receptors that bind and are activated by trace amines was identified in the long arm of chromosome 6q23. We evaluated two families with CH by linkage analysis to 6q23 region and the mutation scanning of the TAR 1, TAR 3, TAR 4, TAR 5, PNR and GPR58 genes by denaturing high liquid chromatography is in progress in 16 familial cases.
Biogenic Amines↗
Multiple sclerosis and gliomas. Clinical remarks on 10 cases and critical review of the literature.
The association between multiple sclerosis and tumours of the central nervous system is unusual. The authors analyzed the clinico-pathological elements of the correlation. The pertinent literature on this subject is critically reviewed. Ten cases of patients with an history of multiple sclerosis for more than 15 years and a clinical and radiological evidence of brain tumour were submitted to surgery in order to remove the lesion and/or to chemo- and radiotherapy. The various aspects of the association were studied in detail. A patient with multiple sclerosis, particularly with atypical symptoms, should be evaluated by an annual MRI investigation with intravenous paramagnetic contrast medium. The diagnostic work-up should be: clinical and radiological assessment; MRI in the event of atypical symptoms; Sstereotactic or neuronavigation-aided biopsy in any suspected lesions. Patients with multiple sclerosis and glioma present survival times identical to those observed in patients not suffering from multiple sclerosis. The coexistence of multiple sclerosis and brain tumours does not seem to influence the clinical evolution of either of these pathologies. We believe that it is important to achieve an early diagnosis of brain tumour in such patients with a clinical and neuroradiological follow up, so that they can be treated promptly.
Adult↗
Treatment of migraine with aura: comments and perspectives.
Migraine with aura (MwA) is a primary headache that affects about 30% of migraine sufferers. The main questions for the physician caring for the patient who has MwA are: when to use preventive medications, what medications to use in acute and preventive treatment, and whether the aura should be treated. The aim of this paper is to review the various therapeutic options for MwA proposed in the current literature and to evaluate their efficacy.
Adolescent↗
Neurogenic inflammation in primary headaches.
The headache in migraine is thought to result from neuronal nociceptive activity in the trigeminovascular system, that is, the meninges. In addition, trigeminal axons projecting to the meninges contain vasoactive neuropeptides, such as substance P, calcitonin gene-related peptide and neurokinin A, that may promote, when released, plasma protein leakage and vasodilation within dura mater, characteristic of neurogenic inflammation. Thus, it has been hypothesized that a sterile neurogenic inflammation in the meninges may be involved in generating or sustaining, via occurrence of a vicious cycle, the pain accompanying the migraine attacks. We here review the evidence in support of this hypothesis as well as its potential significance in better tailoring therapies in migraine or other types of primary headaches.
Animals↗
Elusive amines and primary headaches: historical background and prospectives.
Although the role of trace amines such as tyramine, octopamine and synephrine in the pathogenesis of migraine has been debated for decades, this issue remains still unresolved. In spite of a relevant body of work, the inability to demonstrate specific receptors for these compounds and the lack of sensitive non-radioactive methods for the detection of trace amines in biological samples have limited their investigation in humans. However, the recent identification of a new, large family of G protein-coupled receptors, some of which bind and are activated by trace amines, has focused renewed attention on these compounds. This discovery, together with the possibility of providing novel insights for evaluation of the pathophysiological role of trace amines in primary headaches, may offer new opportunities for pharmacological strategies acting on these receptors. In light of the new scientific background, this review outlines a historical perspective and summarizes evidence supporting a role of trace amines in the pathogenesis of migraine and cluster headache.
Amines↗
Migraine with aura triggered by orgasm.
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Adult↗
Lamotrigine in the treatment of SUNCT syndrome.
Short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is considered an intractable condition. The authors treated five patients with lamotrigine (125 to 200 mg daily), obtaining a complete remission in three patients and a substantial reduction (about 80%) of attack frequency in the other two. No adverse effects were noted.
Adult↗