Biomedical subjects

L Nobili

Publications and source records attributed to L Nobili.

At least 37 records · Page 2Linked to original sources

PubMed2000

Combined treatment with haloperidol and trazodone in patients with tic disorders.

The combination of haloperidol and trazodone was evaluated in an open-label trial in 10 patients with chronic tic and Tourette's syndrome. We found a mean reduction of symptoms of 58.9% on the Yale Global Tic Severity Scale, with a statistically significant difference (p < 0.001) between the baseline and endpoint treatment conditions. This approach significantly reduces clinical symptoms, with the advantage of a lower dose of haloperidol than usual, with no side effects reported by the patients.

Adolescent↗

PubMed2000

Spindles-inducing mechanism modulates sleep activation of interictal epileptiform discharges in the Landau-Kleffner syndrome.

PURPOSE: Landau-Kleffner syndrome (LKS) is characterized by a marked increase of interictal epileptiform discharges (IEDs) during sleep. During nonrapid eye movement (NREM) sleep, neuronal membrane potential oscillations lead to the appearance of spindles and delta waves in the surface EEG and might develop into paroxysmal synchronization. Spectral analysis allows the quantitative description of the dynamics of delta (slow-wave activity, SWA, 0.5-4.5 Hz) and sigma activity (SA, 12.0-16.0 Hz) and can be used to assess the relation between SA, SWA, and IEDs during sleep. METHODS: We performed six overnight continuous EEG-polysomnographic studies in three patients with LKS. The temporal series of SWA and SA were obtained from a spike-free derivation lead. The IEDs count was performed on the most active lead. Relations between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significantly higher correlation between IEDs and SA with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between SA and IEDs. CONCLUSIONS: Our data suggest that neural mechanisms involved in the generation of sleep spindles facilitate IEDs production in LKS.

Age Factors↗

PubMed2000

Morning increase of whole blood viscosity in obstructive sleep apnea syndrome.

OBJECTIVE: Patients affected by obstructive sleep apnea syndrome (OSAS) have an increased risk of cardiovascular diseases such as stroke and myocardial infarction. The pathophysiological mechanisms leading to increased vascular risk are still matter of debate. A relative morning hyperviscosity could be one of the leading mechanisms of cardiovascular morbidity which is actually known to be especially high in the morning hours. METHODS: Whole blood viscosity (WBV) at seven shear rates, ranging from 0.47 to 118 sec(-1), haematocrit (Hct), and plasma fibrinogen (F) concentration, were measured on venous blood samples in 12 patients with OSAS and in 8 healthy controls at 8-9 p.m. and at 7-8 a.m. the morning after. WBV values were normalized on Hct by the computation of the standardised normal deviate z on the normal database of the laboratory. RESULTS: No changes were observed in controls. Hct, F and normalized WBV (independently from Hct changes) significantly increased in the morning hours in OSAS patients. CONCLUSIONS: Viscosity of whole blood increases in the morning in OSAS patients but not in healthy controls. This condition may be related to the increased susceptibility to cerebral ischemia in patients affected by OSAS, particularly evident in the early morning.

Adult↗

PubMed1999

A method for the automatic detection of arousals during sleep.

A method for the automatic detection of arousals in digital polysomnographic recordings is described. The computer program analyzed two EEG and one EMG derivations marking variable length segments as arousals. The processing of EEG data started from the wavelet transform, which characterizes the signal in the time-frequency domain, and resulted in a set of indices used to discriminate possible arousal segments. Transient increases in muscle activity were also identified, while a multichannel and context sensitive analysis allowed arousal detection. Out of 11 overnight recordings, 3 were used as the training set and 8 as the program testing set. In the first stage of the study two EEG experts inspected the tracings independently to score arousals. They then reviewed all recordings and jointly examined each event for validation, both those scored by themselves and those scored by the computer. A reference set of definite arousals (1125 in the testing set) and a number of uncertain events (266) were thus obtained. The sensitivity of the automatic system (88.1%) was higher than that of the human experts (72.4 and 78.4%) while the selectivity was lower (74.5% for the automatic system, 83.0 and 82.0% for the experts). This suggested that automatic detection, followed by an expert's validation, may render the analysis of arousals more widely feasible as well as support the study of arousal features.

Adult↗

PubMed1999

Detection of t(4;14)(p16.3;q32) chromosomal translocation in multiple myeloma by double-color fluorescent in situ hybridization.

Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus at chromosome 14q32 represent a common mechanism of oncogene activation in lymphoid malignancies. In multiple myeloma (MM), variable chromosome partners have been identified by conventional cytogenetics, including the 11q13, 8q24, 18q21, and 6p21 loci. We and others have recently reported a novel, karyotypically undetectable chromosomal translocation t(4;14)(p16. 3;q32) in MM-derived cell lines, as well as in primary tumors. The 4p16.3 breakpoints are relatively scattered and located less than 100 kb centromeric of the fibroblast growth factor receptor 3 (FGFR3) gene or within the recently identified WHSC1 gene, both of which are apparently deregulated by the translocation. To assess the frequency of the t(4;14)(p16.3;q32) translocation in MM, we performed a double-color fluorescent in situ hybridization (FISH) analysis of interphase nuclei with differently labeled probes specific for the IGH locus (a pool of plasmid clones specific for the IGH constant regions) or 4p16.3 (yeast artificial chromosome (YAC) 764-H1 spanning the region involved in breakpoints). Thirty MM patients, the MM-derived cell lines KMS-11 and OPM2, and six normal controls were examined. The identification of a t(4;14) translocation, evaluated as the presence of a der(14) chromosome, was based on the colocalization of signals specific for the two probes; a cutoff value of 15% (mean + 3 standard deviation [SD]) derived from the interphase FISH of the normal controls (range, 5% to 11%; mean +/- SD, 8.16 +/- 2.2) was used for the quantification analysis. In interphase FISH, five patients (one in clinical stage I, two in stage II, one in stage III, and a plasma cell leukemia) were found to be positive (approximately 15%). FISH metaphases with split or colocalized signals were detected in only two of the translocated cases and confirmed the pattern found in the interphase nuclei. Furthermore, in three of the five cases with the translocation, FISH analysis with the IGH joining probe (JH) showed the presence of the reciprocal product of the translocation [der(4) chromosome]. Overall, our study indicates that the t(4;14)(p16. 3;q32) chromosomal translocation is a recurrent event in MM tumors and may contribute towards the detection of this lesion and our understanding of its pathogenetic and clinical implications in MM.

Aged↗

PubMed1999

A quantified analysis of sleep electroencephalography in anorectic adolescents.

BACKGROUND: Previous studies on sleep characteristics in anorexia nervosa have led to controversial results. This may be due to either the heterogeneity of the samples studied or to an intrinsic inadequacy of the scoring criteria. To obtain a more detailed analysis we have investigated sleep characteristics in a group of adolescents affected by anorexia nervosa using spectral analysis techniques. METHODS: After a baseline night, the sleep-electroencephalograms of 10 adolescent anorectic girls (age +/- SD = 14 +/- 2 years) and 10 age-matched control subjects were recorded and processed by a fast Fourier transformation routine. RESULTS: Anorectics showed an increased number of awakenings and wakefulness after sleep onset and a reduction of sleep efficiency and slow-wave sleep. Spectral analysis results revealed a significant reduction in the power spectral values of slow-wave activity (SWA; 0.5-4.5 Hz) band in all NREM-REM cycles of sleep and in the undisturbed and stable stage 4. Moreover the anorectic group was characterized by a concentration of SWA in the first NREM-REM cycle with an abrupt decay in the second part of the night. A positive correlation (r2 = .58, p < .01) between body mass index and the amount of SWA was found. CONCLUSIONS: Sleep of anorectic patients seems to be characterized by a weakness of SWA producing mechanisms. The positive correlation between body mass index and the amount of SWA appears to be consistent with the neurobiological consequences of the malnutrition state.

Adolescent↗

PubMed1999

Correlation dimension of EEG slow-wave activity during sleep in narcoleptic patients under bed rest conditions.

The calculation of the correlation dimension (D2) was applied to the study of the profiles of EEG slow-wave activity in nine narcoleptic subjects and nine sex- and age-matched control subjects who, following a baseline night recording, were maintained on 16 h of diurnal sleep deprivation and, thereafter, submitted to a 32-h bed rest protocol. The reversibility test allowed us to reject the null hypothesis that the time series considered in our study were generated by a static transformation of a linear Gaussian random process. Similarly, all profiles showed a positive largest Lyapunov exponent. Finally, the computation of D2 showed an average value of 5.27 (0.68 S.D.) in normal controls and 4.05 (1.49 S.D.) in narcoleptic patients (p = 0.067). Four of the narcoleptic patients showed values of D2 lower than 4, this was never observed in the normal controls (p = 0.0294). This study indicates that the mechanism of sleep-wake regulation in narcolepsy shows a somewhat lower degree of complexity as compared to normal controls. In particular, these data seem to confirm the already suggested different and simpler coupling between the homeostatic process of sleep regulation and the circadian and ultradian drives to sleep that occurs in bed rest condition in this disease.

Adult↗

PubMed1999

Relationship of sleep interictal epileptiform discharges to sigma activity (12-16 Hz) in benign epilepsy of childhood with rolandic spikes.

OBJECTIVE: The activation of interictal epileptic discharges (IEDs) by NREM sleep is a well-known phenomenon in benign epilepsy of childhood with rolandic spikes (BECRS). The activating properties of NREM sleep on IEDs have been attributed to increased synchronization within thalamocortical neurons. During NREM sleep two synchronizing mechanisms lead to the appearance of spindles and delta waves on the EEG. Spectral analysis technique is a suitable method that can be used to quantitatively describe the dynamics of delta (slow wave activity (SWA) 0.5-4.0 Hz) and sigma activity (12.0-16.0 Hz) during sleep. METHODS: In order to define more accurately the relationship between synchronizing mechanisms (spindles and delta activities) and IEDs during sleep in BECRS, we have performed overnight continuous EEG polysomnography studies in 9 patients (mean age 7.4 +/- 2.5 years). The temporal series of SWA and sigma values, derived from spectral analysis, have been obtained from a spike-free derivation lead. The IEDs count has been performed on the most active lead. Relationships between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significant higher correlation between IEDs and sigma activity with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between sigma and IEDs. CONCLUSIONS: Data suggest that during sleep of BECRS patients, IEDs are more sensitive to the promoting action of the spindle-generating mechanism than to the SWA-producing one.

Brain↗

PubMed1999

Modulation of sleep interictal epileptiform discharges in partial epilepsy of childhood.

OBJECTIVE: NREM sleep increases the Interictal Epileptic Discharges (IEDs) in the majority of children affected by partial epilepsy (both symptomatic or cryptogenetic). Experimental data revealed that the normal sleep oscillations, leading to the appearance of spindles and delta waves on the surface EEG during NREM sleep, might develop into paroxysmal synchronization. Spectral analysis enables the quantitative description of the dynamics of delta (slow wave activity, SWA, 0,5-4,5 Hz) and sigma activity (SA, 12.0-16.0 Hz) and can be used to assess the relationship between SA, SWA and IEDs during sleep. DESIGN AND METHODS: We have performed overnight continuous EEG-polysomnographic studies in 7 patients (mean age 7.2+/-1.3). The temporal series of SWA and SA were obtained from a spike-free derivation lead. The IEDs count was performed on the most active lead. Relationships between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significant higher correlation between IEDs and SA with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between SA and IEDs. CONCLUSIONS: Our data suggest that the neural mechanisms involved in the generation of sleep spindles facilitate the IEDs production in childhood partial epilepsies at least in those strongly activated by sleep.

Brain↗

PubMed1997

Cholinergic modulation, visual function and Alzheimer's dementia.

Electrophysiological evidence at a cellular level and in vivo macroelectrode recordings converge in indicating a degree of specificity of acetylcholine action in vision. Acetylcholine (ACh) function is also thought to play a significant role in memory, learning and other cognitive processes. In this respect, ACh action is suggested to serve in both sensory and cognitive processes. The pharmacological blocking of brain muscarinic transmission has been proposed as a model of geriatric memory impairment and Alzheimer's dementia. Visual electrophysiological testing is deemed of diagnostic specificity for this disease. ACh brain neurotransmission, however, mostly contributes to the modulation of nonspecific aspects of cognition, such as arousal or attention. Alzheimer's dementia results from complex neuron alterations [which also affect muscarinic receptors among other (sub)cellular structures] rather than simply reflecting ACh impoverishment. A substantial loss of retinal ganglion cells is documented in patients with Alzheimer's disease and is consistent with electrophysiological observations. However, it is unclear to what extent the dysfunction of the visual system observable in Alzheimer's dementia is qualitatively different from that occurring spontaneously during aging. The dissimilarities between the effect of acute muscarinic blocking (e.g. by scopolamine) and dementia outnumber the similarities. Accordingly, the conventional ACh agonist-antagonist model of dementia now appears questionable, and replacement treatment with compounds enhancing ACh function proved disappointing. It is suggested that (nonspecific) ACh action becomes function-specific, as determined by the architecture of local brain circuits in which it is involved.

Acetylcholine↗

PubMed1997

Comparison between visual scoring of cyclic alternating pattern (CAP) and computerized assessment of slow EEG oscillations in the transition from light to deep non-REM sleep.

Ten healthy volunteers (six men and four women) aged between 20 and 30 years underwent a nocturnal polygraphic recording on paper and on tape. Spectral analysis was accomplished and EEG sleep scored according to standard criteria and to the guidelines for the identification of cyclic alternating pattern (CAP). The initial 25 min of sleep, starting from the first clear-cut k-complex and ending within stage 4, was subdivided into five consecutive blocks of 5 min each. Using a zero-crossing technique, we evaluated the number of total power oscillations in each block and we tested the hypothesis of significant modifications of the number of total power oscillations and of their periodicity in the successive sessions. In addition, we measured the gap between the maximum and minimum values, respectively, of two successive half-waves making up each oscillation. The hypothesis of time-related trends of the values of the gaps was tested by means of linear regression techniques. Within the 25-min time span, the number of periodic oscillations and the number of CAP cycles showed significant increases. The amplitude gaps underwent a decreasing trend. The present data suggest that slow rhythmic oscillations expressed by CAP can be detected by means of spectral analysis. Their dynamics suggests a close relationship with the EEG synchronization processes.

Adult↗

PubMed1997

An integrated model of sleep regulation.

We present a new model of sleep regulation which integrates the two process model and the limit cycle reciprocal interaction model. In the two process model the interaction of a homeostatic process (S signal) and of a circadian process determines the timing of sleep and waking. In the limit cycle model, the NREM-REM sleep cycle is generated by the reciprocal interaction of two coupled cell population. The present model integrates the two considered models introducing the trigger REM-NREM generated by the REM-ON signal and activated when REM-ON overcomes the S signal.

Cerebral Cortex↗

PubMed1996

Ultradian aspects of sleep in narcolepsy.

Following a baseline night recording, 9 narcoleptic subjects and 9 sex and age-matched control subjects were maintained on 16 hours of diurnal sleep deprivation. Thereafter subjects were submitted to a 32 hour bed rest protocol in a sound-light attenuated room. The EEG was recorded and processed using a Fast Fourier Transform. Narcoleptic patients did not differ from control subjects in total sleep time over the whole time-span. An ultradian tendency to sleep seems to be predominant in narcoleptic patients and evidence of a strong basic rest activity cycle is shown. The coupling between the homeostatic process of sleep regulation and an ultradian drive to sleep would explain the peculiar 4 hour distribution pattern of SWA in narcoleptic patients.

Activity Cycles↗

PubMed1995

Dynamics of slow wave activity in narcoleptic patients under bed rest conditions.

Following a baseline night recording, 9 narcoleptic subjects and 9 sex- and age-matched control subjects were maintained on 16 h of diurnal sleep deprivation. Thereafter subjects were submitted to a 32 h bed rest protocol in a sound- and light-attenuated room. The EEG was recorded and processed by a Fast Fourier Transform. Narcoleptics did not differ from controls in total sleep time over the whole 32 h, but spent more time sleeping during the daytime (DT). In both groups slow wave activity (SWA) showed an exponential decaying trend during the first night (N1); a similar exponential trend during the second night (N2) was evident only in controls. In controls SWA showed a circadian-circasemidian distribution that was hardly detectable in nacroleptics. Narcoleptics showed an ultradian distribution of SWA with periodic emergence every 4 h during DT and N2. Our data confirm that a homeostatic mechanism is evident in narcolpetics when stimulated by diurnal sleep deprivation, while circadian and circasemidian mechanisms are less evident during DT and N2. These findings suggest a different coupling between homeostatic sleep regulating and circadian drives to sleep in narcoleptics. Ultradian drives to sleep seem to be predominant in these patients, thus probably acting as a means for the avoidance of stressful attempts to counteract a weaker waking state maintenance mechanism.

Adult↗

PubMed1992

Differential expression of very late activation antigen-3 (VLA-3)/VLA-4 in B-cell non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia.

The expression of beta 1 (very late activation antigens, VLA 1-6) and beta 2 integrins (leukocyte adhesion molecules [Leu-CAM]) in cell suspensions from the peripheral blood of 70 patients with B-cell chronic lymphocytic leukemia (B-CLL), 15 patients with leukemic lymphocytic lymphoma of intermediate differentiation (IDL), as well as from the lymph nodes of 20 patients with low/intermediate-grade non-Hodgkin's lymphoma (NHL) was studied with the aim of characterizing their adhesive phenotype and evaluating its relationship to clinical behavior. CD11a(LFA-1) was more expressed in NHL and IDL than in B-CLL (P = .047), although it was demonstrable in 74.2% of cases; CD11c was more expressed in B-CLL (P less than .0001), and its expression was preserved in almost all of the cases of small lymphocytic lymphoma. In NHL patients, including the cases of IDL, VLA-3 expression was observable in 8 of 35 cases (although always at a low level of intensity), while VLA-4 was almost constantly expressed in a way that was similar to its expression in control normal B cells. On the contrary, in B-CLL patients, VLA-3 was expressed (prevalently at high levels) in 87.1% of cases and VLA-4 only in 37.1%. No correlation was found between adhesion molecule patterns and the clinical features of the diseases. The biofunctional significance of the imbalance of VLA-3 and VLA-4 expression in B-CLL is not easy to explain, but it has undoubted intrinsic value as an additional marker for distinguishing B-CLL from, in particular, those B-cell neoplasms (such as IDL) that share many of the immunocytomorphologic characteristics and the putative normal counterpart (the mantle zone) of B-CLL.

Antigens, CD↗

PubMed1990

Immunophenotypes in "classical" B-cell chronic lymphocytic leukemia. Correlation with normal cellular counterpart and clinical findings.

This study evaluates the expression of a series of membrane antigens, normally expressed by B-lymphocytes of the lymphocytic mantle and marginal zone, in 90 selected cases of "classical" (mouse red blood cell-receptor+, CD20+, CD5+, surface immunoglobulin +/-) B-chronic lymphocytic leukemia (B-CLL) with the aim of contributing toward identifying the normal counterpart of B-CLL and any correlations between surface antigen pattern and certain clinical characteristics. Clustered (CD23, 25, 39, 40, 27, 1c, w75) and unclustered (NuB1, 7F7, KiB3) monoclonal antibodies (MoAb) were tested. Almost all cases showed high reactivity to CD23, 27, w75, 39, 40, and NuB1: expression of CD1c was very low and that of 7F7, KiB3, and CD25 was variable. The reactivity of 7F7 and KiB3 was strictly correlated, and they correlated individually with CD25. Results show that the most frequent B-CLL phenotype (CD19+, 5+, 23+, 27+, 39+, NuB1+, KiB3 +/-, 7F7 +/-, and CD25 +/-) corresponds to one or more cellular subsets in the mantle zone. No correlation was found between MoAb expression, surface immunoglobulin (SIg) class or type, clinical stage, disease activity, or age at diagnosis. The only difference (statistically borderline) was the expression of 7F7 and KiB3 (in young versus old patients). This suggests that modulations in the expression of surface antigens do not affect the clinical behavior of the disease.

Adult↗

PubMed1986

Human recombinant interferon alpha-2C enhances the expression of class II HLA antigens on hairy cells.

Isolated splenic hairy cells from three untreated patients were cultured in presence of recombinant human interferon alpha-2C (IFN alpha). Ultrastructural cytochemistry and immunophenotype analysis with a large panel of monoclonal antibodies were performed to study cellular modification induced by IFN alpha. Hairy cells showed a typical pheno-type: Smlg+, B1+, BA1+/-, anti-Tac+, OKDR+, Leu-M5+, HC2+, TRAP+, myeloperoxidase-. Under our experimental conditions, we found no direct cytotoxic effects or significant variations in morphology, cytochemistry, and percentage of reactivity with the tested monoclonal antibodies. After culturing in the presence of different doses of IFN alpha, we observed a significant enhancement of the expression of class II HLA antigens as demonstrated by increased fluorescence for OKDR, OKla, Leu-10 at fluorescence-activated cell sorting analysis. In agreement with this finding IFN alpha-treated hairy cells showed an increased stimulatory capacity v allogeneic T cells in one-way mixed lymphocyte reaction. To our knowledge this is the first report describing the induction of class II HLA antigens on hairy cells by IFN alpha.

Antibodies, Monoclonal↗

PubMed1985

Functional and multimarker analysis of T-cell chronic lymphocytic leukaemia.

The morphology, immunophenotype, cytoenzymatic and functional activities of T lymphocytes from 4 patients with chronic lymphoproliferative disease of T-cell origin were studied. Clonal proliferation was demonstrated by distinctive chromosomal abnormalities involving chromosomes 2 and 14. Patients 1 and 2 were classifiable as OKT4+ T-cell chronic lymphocytic leukaemia (T-CLL) and patient 3 as OKT4+/OKT8+ T-CLL, with helper function in vitro only in patient 1. Patient 4 has low-grade lymphocytosis with benign clinical course, with cells showing morphology of large granular lymphocytes (LGL), and immunophenotype HNK-1+, ER+, Fc gamma receptor+, OKT3+, OKT11+ and OKT8+, as well as natural killer activity, radiosensitive suppressor activity on Ig secretion and responsiveness to PHA; this case was interpreted as LGL leukaemia. This study indicates that a large proportion of cases of true T-CLL may belong to the OKT4 subset, and that extensive investigations should be made of the lymphocytic OKT8+/T gamma forms to characterize them precisely.

Aged↗