Search PubMed⌕ Search

Biomedical subjects

R Guerrini

Publications and source records attributed to R Guerrini.

At least 127 records · Page 7Linked to original sources
PubMed1999

Piracetam in the treatment of cortical myoclonus.

This paper reviews existing publications on the use of piracetam for the treatment of cortical myoclonus of various etiologies and includes the personal experience of the authors in progressive myoclonus epilepsy. Two double-blind comparisons with placebo provided results which allow recommendations for the dosage and usage of piracetam in cortical myoclonus. Wide individual variation (7-24g daily) exists in dosage requirements but responses are dose-related so that dosage should be increased until an optimum effect is obtained. Tolerability after long-term use of piracetam in high dosage has been very good and without toxicity or serious adverse effects. Side effects have been occasional, mild and transient. The authors present their experience of 12 patients with progressive myoclonus epilepsy in whom the administration of up to 45 g piracetam daily, when added to existing anti-epileptic treatment, caused marked and sometimes spectacular improvement and was without significant adverse effects. Improvement was maintained for up to 7 years. The use of piracetam for disabling cortical myoclonus of any etiology, either as an addition to existing antimyoclonic drugs or as monotherapy, may bring about profound improvement in disability and quality of life. Piracetam should be considered a first-line drug for the treatment of cortical myoclonus.

Clinical Trials as Topic↗
PubMed1999

No evidence of a major locus for benign familial infantile convulsions on chromosome 19q12-q13.1.

PURPOSE: A locus for benign familial convulsions (BFICs) has been recently mapped on chromosome 19q12-13.1 by studying five families of Italian descent. The main goal of this study was to investigate the role of this locus in a set of seven newly identified families with at least three affected cases. METHODS: Five polymorphic microsatellite markers covering the BFIC locus on chromosome 19q have been typed, and parametric linkage analysis has been performed to analyze the segregation of the BFIC locus within our families. RESULTS: Cumulative 2-point lod scores and multipoint analysis showed no evidence of linkage between chromosome 19 markers and the BFIC phenotype. The analysis of family-specific 2-point lod scores and haplotypes, however, indicated the presence of linkage to chromosome 19q in a single family, suggesting genetic heterogeneity within our family sample. CONCLUSIONS: Our study demonstrates that the previously reported BFIC locus on chromosome 19q12-13.1 is not a major locus for BFICs. We suggest that genetic heterogeneity may have generated our discordant linkage findings, as it was reported in benign familial neonatal convulsions, a related idiopathic mendelian syndrome.

Chromosome Mapping↗
PubMed1999

Familial epilepsy with unilateral and bilateral malformations of cortical development.

PURPOSE: To describe a family in whom two sisters with epilepsy, mental retardation, and microcephaly had different malformations of cortical development detected by magnetic resonance imaging (MRI). METHODS: Clinical investigation of the patients and their family. High-resolution MRI, cognitive testing, and repeated EEG recording in both patients. RESULTS: In one patient, the malformation was bilateral and diffuse but much more pronounced in the parietal and occipital regions, with MRI characteristics indicating pachygyria-polymicrogyria. In the other patient, the abnormality involved the right hemisphere, predominating around the perisylvian region, with MRI more clearly indicative of polymicrogyria. A brother also had severe epilepsy, diffuse EEG abnormalities, mental retardation, and microcephaly, but could not be studied neuroradiologically. CONCLUSIONS: Lack of MRI studies in the parents and brother does not allow a precise hypothesis on the mode of transmission. However, findings from this family indicate that unilateral malformations of cortical development detected during investigations after seizure onset may be genetically based, suggesting that a single genetic abnormality could be responsible for bilateral or unilateral malformations.

Adult↗
PubMed1999

Continuous spike-and-wave activity during slow-wave sleep: syndrome or EEG pattern?

PURPOSE: We reviewed the electroclinical pictures and clinical characteristics of 32 patients with continuous spike-and-wave activity during slow sleep (CSWS) to ascertain to what extent this electroencephalogram (EEG) pattern is associated with the age-related CSWS syndrome as defined by the International League Against Epilepsy (ILAE) International Classification or with different clinical settings. METHODS: We reviewed clinical and EEG characteristics of 32 CSWS patients. RESULTS: In all patients, detection of CSWS coincided with a worsening of neurologic status. Ten (34%) patients had the typical features of CSWS syndrome, four were classified as having Landau-Kleffner syndrome, and three had acquired opercular syndromes. The remaining 15 patients, all with symptomatic epilepsy, had CSWS, which lasted for variable periods and might be related to inappropriate drug choice. Three patients of this group had unilateral CSWS and exhibited worsening of spontaneous movements in the hemibody contralateral to CSWS activity lasting for a few hours after awakening. CONCLUSIONS: Our data show that a number of factors can intervene in the genesis of CSWS, which may explain the variability of the associated clinical conditions. In view of this etiologic heterogeneity, it is not possible to classify all the patients with CSWS as having the CSWS syndrome. Therefore, the CSWS syndrome should be considered a category embracing a limited group of patients, whereas the EEG pattern of CSWS is seen commonly in various clinical conditions.

Adolescent↗
PubMed1999

Cardiovascular effects of nociceptin in unanesthetized mice.

We evaluated the systemic hemodynamic effects induced by nociceptin (NC) and NC-related peptides, including the NC receptor antagonist [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) in unanesthetized normotensive Swiss Morini mice. Bolus intravenous injection of NC decreased mean blood pressure and heart rate. The hypotensive response to 10 nmol/kg NC lasted <10 minutes, whereas a more prolonged hypotension was evoked by 100 nmol/kg (from 114+/-3 to 97+/-2 mm Hg at 10 minutes, P<0.01). The latter dose reduced heart rate from 542+/-43 to 479+/-31 beats/min (P<0.05) and increased aortic blood flow by 41+/-5% (P<0.05). Hypotension and bradycardia were also evoked by NC(1-17)NH2 and NC(1-13)NH2 fragments, whereas NC(1-13)OH and NC(1-9)NH2 were ineffective. Thiorphan, an inhibitor of neutral endopeptidase 24.11, enhanced the hypotension induced by NC(1-13)NH2 and revealed the ability of NC(1-13)OH to decrease mean blood pressure. [F/G]NC(1-13)NH2, a recently synthesized antagonist of the NC receptor, did not alter basal mean blood pressure or heart rate, but it prevented the hypotension, bradycardia, and increase in aortic blood flow evoked by NC. In contrast, [F/G]NC(1-13)NH2 did not alter the hypotension induced by bradykinin or endomorphin-1 (a micro-receptor agonist), and the bradycardia induced by leu-enkephalin (a delta-receptor agonist) or U504885 (a synthetic kappa-receptor agonist). In conclusion, NC and some of its fragments cause hypotension and bradycardia and increase aortic blood flow in mice, with the NC(1-13) sequence being critical for these biological effects. Our results also demonstrate that the compound [F/G]NC(1-13)NH2 is a potent and selective antagonist of the NC receptor in vivo.

Animals↗
PubMed1999

Epilepsy and malformations of the cerebral cortex.

Abnormal cortical development is increasingly recognized as a cause of human epilepsy. Development of the cerebral cortex involves three distinct but overlapping processes consisting of neuronal and later glial proliferation, neuronal migration and cortical organization. Cortical malformations can originate from abnormalities of any or all of these processes. Certain malformations are known to be genetically determined, while for others a genetic origin has been hypothesized. In addition, there are some that may be linked to prenatal insult. Some malformations are notably more epileptogenic than others. In specific forms, epileptogenesis appears to originate from intrinsic properties of the dysplastic tissue, and is stereotyped in expression. Cortical malformations are also known that are affected by age-related influence and may be accompanied by different epileptic syndromes, sometimes with good long-term outcome. In patients with intractable seizures which are symptomatic of a cortical malformations it is necessary to diagnose the type of malformation and the associated epileptic syndromes and to assess the characteristics of epileptogenesis. Planning of surgical treatment of the associated epilepsy must rely on careful evaluation of all these informations.

Cerebral Cortex↗
PubMed1999

L-glutamate and gamma-aminobutyric acid efflux from rat cerebrocortical synaptosomes: modulation by kappa- and mu- but not delta- and opioid receptor like-1 receptors.

The modulation by delta-, kappa-, mu-, and opioid receptor like-1 (ORL(1)) agonists and antagonists of L-glutamate (L-Glu) and gamma-aminobutyric acid (GABA) efflux from superfused rat cerebrocortical synaptosomes was studied. Tetrodotoxin (0.5 microM) inhibited the spontaneous efflux of both transmitters by 20%. Ca(2+) omission decreased GABA and facilitated L-Glu efflux. The neurotransmitter overflow evoked by K(+) concentrations in the 7.5- to 10-mM range was largely Ca(2+) dependent and tetrodotoxin sensitive. Neither the delta-receptor agonist deltorphin (up to 0.3 microM) nor the ORL(1) receptor agonist nociceptin (up to 1 microM) significantly affected either spontaneous or K(+)-evoked neurotransmitter efflux. Conversely, the ORL(1) ligand [Phe(1)(CH(2)-NH)Gly(2)]nociceptin(1-13)NH(2) (0.3 microM) caused a naloxone-sensitive inhibition of both L-Glu- and GABA-stimulated overflow. The kappa-receptor agonist (-)-U50,488 failed to modulate spontaneous L-Glu and GABA efflux. However, it similarly inhibited the K(+)-evoked overflow of both neurotransmitters (EC(50) approximately 100 nM; E(max) approximately 25-30% inhibition) in a norbinaltorphimine-sensitive manner. The selective mu-receptor agonist endomorphin 1 inhibited both spontaneous (EC(50) approximately 50 nM) and K(+)-evoked (EC(50) approximately 10 nM; E(max) approximately 50% inhibition) L-Glu efflux in a naloxone-sensitive manner. Conversely, it significantly inhibited only K(+)-evoked GABA efflux (EC(50) approximately 10 nM), although with a lower maximal effect (E(max) approximately 25-30% inhibition). It is concluded that, in the rat cerebral cortex, L-Glu and GABA efflux from nerve terminals is under the direct inhibitory control of kappa- and mu- (but not delta- or ORL(1)) receptors. Because glutamatergic terminals emerged as a preferential target of mu-receptor agonists, the activation of this receptor may advocate both relevant analgesic and neuroprotective effects.

Animals↗
PubMed1999

Idiopathic partial epilepsy: electroclinical demonstration of a prolonged seizure with sequential rolandic and occipital involvement. Seizure spread due to regional susceptibility?

Benign rolandic epilepsy (BRE) and childhood epilepsy with occipital paroxysms (CEOP) are overlapping in age range of presentation. Some children have been reported to manifest occipital and rolandic seizures, as distinct events. However, the presence during the same seizure of rolandic and occipital symptoms is exceptional. We present a 7-year-old boy with BRE in whom we video-EEG recorded two seizures at 4 years of age. The first episode was a classic rolandic seizure during sleep, while the second was prolonged with initial rolandic and late occipital involvement. It is possible that a rolandic seizure, in a child within the age range of both BRE and early onset CEOP, could spread to selectively involve the occipital lobe, because there is susceptibility of cortical neurons of both areas to develop seizures at this age in idiopathic partial epilepsies.

Brain Mapping↗
PubMed1999

Intracellular levels of the LIS1 protein correlate with clinical and neuroradiological findings in patients with classical lissencephaly.

We report on the genotype-phenotype correlation in 7 patients with classical lissencephaly carrying a heterozygous subtle mutation in the LIS1 gene. Six patients, showed a mutation predicted to encode for a truncated protein, and one mutation altered a splicing site, resulting in skipping of exon 4. Western blot analysis performed on the lymphoblastoid cell line of 2 patients bearing truncating mutations indicated that the mutated allele did not produce a detectable amount of the LIS1 protein; whereas the analysis performed on the fibroblasts from the patient with a splice-site mutation was suggestive of partial protein synthesis from the mutated allele. Although clinical and magnetic resonance imaging findings of patients with truncating mutations did not differ from those observed in patients with a heterozygous deletion, the patient bearing the exon-skipping mutation had less severe clinical and brain involvement. Our data suggest that truncating mutations in the LIS1 gene are relatively common among patients with classical lissencephaly not bearing a heterozygous deletion at 17p13.3, and strengthen the relevance of correct intracellular dosage of the LIS1 protein in the neuronal migration process.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

Structure-activity study of the nociceptin(1-13)-NH2 N-terminal tetrapeptide and discovery of a nociceptin receptor antagonist.

In the present study, the minimal fragment sequence required to fully activate the nociceptin (NC) receptor, namely NC(1-13)-NH2, was used as template for the design of a series of new compounds. Changes were made in the N-terminal tetrapeptide Phe-Gly-Gly-Phe, which has been shown to be essential for receptor occupation and activation. The new compounds were tested for their ability to inhibit the electrically evoked contraction of the mouse vas deferens, a pharmacological preparation sensitive to NC. Results obtained indicate that (a) the replacement of Gly2 or Gly3 with an aromatic residue (Phe) of L or D chirality eliminates the ability of the peptide to occupy the NC receptor; (b) the distance between Phe1 and Phe4 of NC appears to be critical, since any alteration of it leads to a marked decrease or a total elimination of biological activity; and (c) the insertion of a pseudopeptide bond between Phe1 and Gly2 maintains affinity but eliminates the ability of the peptide to activate the NC receptor and leads to antagonism. The peptide [Phe1psi(CH2-NH)Gly2]-NC(1-13)-NH2 acts as a selective NC receptor antagonist and is inactive on opioid receptors. The results summarized in this paper confirm and extend our previous findings by showing that the structural requirements for NC binding to its receptor are clearly different from those of opioids; in addition, this structure-activity study has led to the identification of the first NC receptor selective antagonist.

Animals↗
PubMed1998

Identification of an immunodominant IgE epitope of the Parietaria judaica major allergen.

Par j 1.0101 is one of the two major allergens of the Parietaria judaica (Pj) pollen, and its three-dimensional structure was built by three-dimensional structural homology modeling. The resultant model was used to identify putative IgE binding regions. Western blot analysis of gene fragmentation products showed that the 1 to 30 region was capable of binding specific IgE from a pool of sera (n = 30) of patients allergic to Pj pollen. Using the structural model as a guide, deletion and site-directed mutagenesis of the 1 to 30 region was performed, and the amino acids involved in IgE binding were identified. In addition, a synthetic peptide covering the 1 to 30 region was capable of binding human IgE without triggering histamine release from basophils of Pj allergic patients (n = 6) and thus represents a haptenic molecule with potential use as an immunotolerant agent. This epitope is also present on the Par j 2.0101 major allergen representing a common IgE epitope. It is an immunodominant epitope, since it was capable of inhibiting 30% of all specific IgE against the Pj major allergens, and therefore, it might be a candidate for the future development of immunotherapeutics.

Allergens↗
PubMed1998

High structural side chain specificity required at the second position of immunogenic peptides to obtain stable MHC/peptide complexes.

Peptides binding to HLA-A11 contain a hydrophobic or a small polar amino acid at position 2 and a lysine at the carboxy terminus. Synthetic peptides carrying natural and unnatural amino acids in position 2 were used to determine the requirements for formation of stable HLA-A11/peptide complexes. By kinetic analysis we demonstrate that a stereospecific interaction between the side chain residue in position 2 and a subsite of pocket B is required to obtain stable HLA/peptide complexes. This specific interaction is mediated by a methyl group or by an ethyl group bound to the asymmetric Cbeta atom with the correct configuration. Experiments performed with different peptide sequences suggest that the presence of adequate anchor residues may be sufficient to produce stable HLA/peptide complexes.

Cell Line↗
PubMed1998

Cortical reflex myoclonus in Rett syndrome.

Rett syndrome (RS) is one of the most frequent causes of mental retardation in females. As there are no known biochemical, genetic, or morphological markers, diagnosis is based on clinical phenotype including severe dementia, autism, truncal ataxia/apraxia, loss of purposeful hand movements, breathing abnormalities, stereotypies, seizures, and extrapyramidal signs. Myoclonus, although reported in some series, has never been characterized. We studied 10 RS patients, age 3 to 20 years, and observed myoclonus in 9. Severity of myoclonus did not correlate with that of the other symptoms or with age. Multifocal, arrhythmic, and asynchronous jerks mainly involved distal limbs. Electromyographic bursts lasted 48 +/- 12 msec. Burst-locked electroencephalographic averaging generated a contralateral centroparietal premyoclonus transient preceding the burst by 34 +/- 7.2 msec. Motor evoked potentials showed normal latencies, indicating integrity of the corticospinal pathway. Somatosensory evoked potentials were enlarged. The C-reflex was hyperexcitable and markedly prolonged (62 +/- 4.3 msec), mainly due to increase in cortical relay time (28.4 +/- 4.5 msec). We conclude that RS patients show a distinctive pattern of cortical reflex myoclonus with prolonged intracortical delay of the long-loop reflex.

Adolescent↗
PubMed1998

Angelman syndrome: correlations between epilepsy phenotypes and genotypes.

We compared epilepsy phenotypes with genotypes of Angelman syndrome (AS), including chromosome 15q11-13 deletions (class I), uniparental disomy (class II), methylation imprinting abnormalities (class III), and mutation in the UBE3A gene (class IV). Twenty patients were prospectively selected based on clinical cytogenetic and molecular diagnosis of AS. All patients had 6 to 72 hours of closed-circuit television videotaping and digitized electroencephalogrpahic (EEG) telemetry. Patients from all genotypic classes had characteristic EEGs with diffuse bifrontally dominant high-amplitude 1- to 3-Hz notched or triphasic or polyphasic slow waves, or slow and sharp waves. Class I patients had severe intractable epilepsy, most frequently with atypical absences and myoclonias and less frequently with generalized extensor tonic seizures or flexor spasms. Epileptic spasms were recorded in AS patients as old as 41 years. Aged-matched class II, III, and IV patients had either no epilepsy or drug-responsive mild epilepsy with relatively infrequent atypical absences, myoclonias, or atonic seizures. In conclusion, maternally inherited chromosome 15q11-13 deletions produce severe epilepsy. Loss-of-function UBE3A mutations, uniparental disomy, or methylation imprint abnormalities in AS are associated with relatively mild epilepsy. Involvement of other genes in the chromosome 15q11-13 deletion, such as GABRB3, may explain severe epilepsy in AS.

Adolescent↗
PubMed1998

Paroxysmal tonic upgaze of childhood with ataxia: a benign transient dystonia with autosomal dominant inheritance.

Paroxysmal tonic upgaze of childhood with ataxia is a rare form of age related dystonia. Out of 12 previously reported cases, three had a clinical history of similar symptoms occurring in at least one first degree relative belonging to the same or two consecutive generations. Autosomal dominant inheritance was therefore hypothesized. We report on a family in which the disorder appeared in three consecutive generations between ages 6 and 11 months, disappearing gradually and spontaneously between ages 18 to 24 months. All affected individuals had normal neurologic development. The pedigree analysis of previously reported cases and of the family reported herein provides strong evidence that the disorder may be inherited as an autosomal dominant trait and represents a form of transient paroxysmal dystonia with benign long-term prognosis.

Ataxia↗
PubMed1998

Seizures in Klinefelter's syndrome.

This study describes the clinical spectrum of patients with Klinefelter's syndrome and seizures. Klinefelter's syndrome is a sex chromosomal abnormality and the most common cause of male hypogonadism. It is characterized by cognitive dysfunction, hypogonadism, and abnormalities of physical maturation. Neurologic impairment has been recognized, but seizures have received little attention. The authors describe three American patients and discuss nine additional patients from two European centers previously reported with Klinefelter's syndrome and seizures. The most common profile of patients with Klinefelter's syndrome and seizures includes mental retardation, behavior problems, epileptiform electroencephalograms (EEGs), and generalized tonic-clonic seizures. The seizures of six of 11 patients with epilepsy were well controlled with antiepileptic drugs. One patient had a single seizure and was not treated with medication. In patients with Klinefelter's syndrome and recurrent seizures, the electroclinical spectrum is heterogenous and outcome with antiepileptic drug treatment is favorable.

Adolescent↗
PubMed1998

Rational design of dynorphin A analogues with delta-receptor selectivity and antagonism for delta- and kappa-receptors.

Substitution of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) in place of Gly2 in dynorphin A-(1-13)-NH2 and -(1-11)-NH2 (DYN) analogues (1 and 2) decreased the affinity to the kappa, delta, and mu receptors, and kappa selectivity. The analogue [D-Ala2, des-Gly3]DYN (4), a chimera between deltorphin/dermorphin N-terminal tripeptide and DYN, was virtually inactive for kappa-sites while the affinities for delta- and mu-receptors remained essentially unchanged. The doubly substituted analogue [2',6'-dimethyl-L-tyrosine (Dmt1)-Tic2]DYN (3) exhibited high delta-affinity (Ki=0.39 nM) while mu- and kappa-affinities were only an order of magnitude less (4-5 nM). Bioactivity of [Tic2]DYN peptides (1-3) on guinea-pig ileum and rabbit jejunum revealed potent delta- and kappa-antagonism, while the delta agonist potency of 4 was comparable to DYN. Thus, conversion from a kappa-agonist to antagonist occurred with the inclusion of Tic into DYN analogues, similar to the appearance of antagonist properties with delta- and mu-opioid agonists containing a Tic2 residue.

Analgesics, Opioid↗