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Biomedical subjects

S Oddo

Publications and source records attributed to S Oddo.

15 recordsLinked to original sources

Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: a role for intraneuronal amyloid.

The amyloid Abeta-peptide (Abeta) is suspected to play a critical role in the cascade leading to AD as the pathogen that causes neuronal and synaptic dysfunction and, eventually, cell death. Therefore, it has been the subject of a huge number of clinical and basic research studies on this disease. Abeta is typically found aggregated in extracellular amyloid plaques that occur in specific brain regions enriched in nAChRs in Alzheimer's disease (AD) and Down syndrome (DS) brains. Advances in the genetics of its familiar and sporadic forms, together with those in gene transfer technology, have provided valuable animal models that complement the traditional cholinergic approaches, although modeling the neuronal and behavioral deficits of AD in these models has been challenging. More recently, emerging evidence indicates that intraneuronal accumulation of Abeta may also contribute to the cascade of neurodegenerative events and strongly suggest that it is an early, pathological biomarker for the onset of AD and associated cognitive and other behavioral deficits. The present review covers these studies in humans, in in vitro and in transgenic models, also providing more evidence that adult 3xTg-AD mice harboring PS1M146V, APPSwe, tauP301L transgenes, and mimicking many critical hallmarks of AD, show cognitive deficits and other behavioral alterations at ages when overt neuropathology is not yet observed, but when intraneuronal Abeta, synaptic and cholinergic deficits can already be described.

Alzheimer Disease↗

Clinical-electroencephalogram patterns at seizure onset in patients with hippocampal sclerosis.

OBJECTIVE: The purpose of this study is to identify specific clinical-electroencephalogram (EEG) patterns at seizure onset in patients with hippocampal sclerosis (HS). METHODS: Sixty-six ictal video-EEG recordings corresponding to 26 patients with HS have been reviewed, focusing on the EEG features found during the first 30 ictal s. The EEG activity has been classified into the following groups: (A) according to spatial distribution: type 1: temporal electrodes on one side; type 2: temporal and adjacent frontal electrodes on one side; and type 3: non-lateralizing electrographic activity; and (B) according to morphology; subtype (a): regular 5-9 Hz rhythmic activity (RA); subtype (b): low-voltage rapid activity, followed by a 5-9 Hz RA; and subtype (c): irregular EEG sharp waves. We analyzed the clinical symptoms sequence and established the relationship with the ictal EEG patterns. RESULTS: Considering spatial distribution and morphology, the most frequent ictal EEG patterns were type 1 (57%), type 2 (37%), and subtype (a): 62%; subtype (b): 27%; and subtype (c): 11%. The sequence of clinical symptoms observed was: aura-->behavioral arrest-->oro-alimentary automatisms-->unilateral hand automatisms. All seizures with aura and including two or more symptoms of the clinical sequence (65%) were associated with a 1a, 1b, 2a or 2b EEG pattern. CONCLUSIONS: The identification of a specific clinical-EEG pattern provides a useful tool for the epileptogenic zone localization in non-invasive pre-surgical assessment of patients with hippocampal sclerosis. SIGNIFICANCE: The identification of a specific clinical-EEG pattern associated to neuroimaging findings and neuropsychological testing allows indicating surgery for the treatment of epilepsy in patients with hippocampal sclerosis, without performing any further complementary studies.

Adult↗

Spike-and-wave complexes and seizure exacerbation caused by carbamazepine.

The purpose of this research is to analyse patients in whom carbamazepine (CBZ) therapy adversely affected electroencephalogram (EEG) recordings leading to seizure exacerbation and to identify risk factors for these events. From a total number of 2191 patients (p.) included in the Municipal Epilepsy Center (MEC) database, 77 patients with spike-and-wave (SW) discharges while on CBZ treatment have been selected. Patient population was divided in two groups: (i) patients who were already receiving CBZ at the time of their first visit to the MEC; and (ii) patients to whom CBZ was prescribed during follow-up at the MEC. CBZ was discontinued in all patients with confirmed evidence of an increase in seizure frequency, or with no improvement of epilepsy. During follow-up, EEG findings as well as all clinical changes were duly recorded. Group 1: Carbamazepine was discontinued in 17 patients (p.) as a result of paradoxical reactions. This condition occurs when an antiepileptic drug (AED) appears to exacerbate a type of seizure against which it is usually effective, or when it leads to the onset of new types of seizures. Three p. were withdrawn because of inappropriate drug selection. Group 2: CBZ was discontinued in six patients (p.) as a result of paradoxical reactions. The paradoxical reaction was more frequent in patients with frontal epilepsy and generalized SW discharges on the EEG (P=0.09) and patients with benign rolandic epilepsy (BRE) with diffuse interictal sharp and slow-wave discharges. In both groups, clinical and electrical changes returned to their initial status upon CBZ withdrawal. On the basis of this study, it may be concluded that EEGs might eventually help to screen high-risk patients. If EEG recordings become substantially worse, with more frequent and longer generalized SW bursts after initiation of CBZ therapy, patients should be carefully monitored in order to detect any sign of clinical impairment.

Adolescent↗

Clinical features and prognosis of nonepileptic seizures in a developing country.

PURPOSE: To determine the predictive value of clinical features and medical history in patients with nonepileptic seizures (NESs). METHODS: One hundred sixty-one consecutive ictal video-EEGs were reviewed, and 17 patients with 41 NESs identified. NES diagnosis was defined as paroxysmal behavioral changes suggestive of epileptic seizures recorded during video-EEC without any electrographic ictal activity. Clinical features, age, sex, coexisting epilepsy, associated psychiatric disorder, social and economic factors, delay in reaching the diagnosis of NES, previous treatment, and correlation with outcome on follow-up were examined. RESULTS: The study population included 70% female patients with a mean age of 33 years. Mean duration of NESs before diagnosis was 9 years. Forty-one percent had coexisting epilepsy. The most frequent NES clinical features were tonic-clonic mimicking movements and fear/anxiety/hyperventilation. The most common psychiatric diagnosis was conversion disorder and dependent and borderline personality disorder. Seventy-three percent of patients with pure NESs received antiepileptic drugs (AEDs), and 63.5% of this group received new AEDs. Fifty-nine percent of the patients received psychological/psychiatric therapy. At follow-up, 23.5% were free of NESs. CONCLUSIONS: All seizure-free patients had two good prognostic factors: having an independent lifestyle and the acceptance of the nonepileptic nature of the episodes. Video-EEG monitoring continues to be the diagnostic method to ensure accurate seizure classification. Establishing adequate health care programs to facilitate access to new technology in public hospitals as well as the implementation of continuous education programs for general practitioners and neurologists could eventually improve the diagnosis and treatment of patients with NESs.

Adolescent↗

Texture segregation in chromatic element-arrangement patterns.

An element-arrangement pattern is composed of two types of elements arranged differently in different regions of a pattern. Rapid texture segregation depends on spontaneously discriminating the difference in the arrangement of the elements. Five experiments investigated the perceived segregation of patterns composed of two types of squares arranged in vertical stripes in the top and bottom regions and in a checkerboard arrangement in the middle region. The squares were either equal in luminance and different in hue or equal in hue and different in luminance. The rated similarities of the two hues in a pattern failed to predict perceived segregation. For a given background luminance, the perceived segregation was predicted by the square-root of the sum of the squares of the differences in the outputs of the L - M + S and L + M - S opponent channels, where L, M, and S were the cone contrasts of the long-, medium-, and short-wavelength receptors. The perceived similarity of the two hues in a pattern was not affected by the background luminance but was a function of cone excitations instead. For patterns differing in hue and equal in luminance, perceived segregation was an inverse function of the background luminance. A white background decreased the perceived segregation, but a black background did not. The effect of background luminance was not on the discrimination of the individual hues. The two hues making up a texture pattern were clearly distinguishable on a white background. A white background interfered with the discrimination of the vertical and diagonal columns of squares that distinguished the texture regions. For patterns differing in luminance and equal in hue, black and white backgrounds decreased the perceived segregation. The results indicate that adapting to an achromatic luminance distant from the luminance of the squares increased the Weber threshold for discriminating luminance differences, but did not increase the Weber threshold for discriminating hue differences. The experiments also revealed that luminance was the primary factor affecting perceived segregation and that perceived brightness is secondary. The results are consistent with the hypothesis that perceived segregation in element-arrangement patterns is primarily a function of the differences in the outputs of relatively early filtering mechanisms that encode pattern differences prior to the specification of the element shapes and their properties.

Color Perception↗

Genetic susceptibility to experimental autoimmune uveoretinitis in the rat is associated with an elevated Th1 response.

This study examines whether genetic susceptibility vs genetic resistance to experimental autoimmune uveoretinitis (EAU) are connected to a predisposition to mount a Th1-dominated (IFN-gamma high, IL-4 low) vs a Th2-dominated (IL-4 high, lFN-gamma low) response. Lewis rats developed disease with high incidence after immunization with the uveitogenic peptide R16, whereas F344 rats were resistant. Primed lymph node cells from both strains proliferated in culture in response to R16. However, while the Lewis cultures transferred EAU to syngeneic recipients, those of F344 did not. The Lewis cultures produced substantially more IFN-gamma mRNA and protein in response to R16, than did those of F344. Both strains made low levels of IL-10 mRNA and IL-4 mRNA. Unlike the primary cultures, long-term (R16-specific) T cell lines derived from each of the strains transferred EAU equally well to their respective recipients, and produced similar, high levels of IFN-gamma mRNA and protein. Treatment of F344 with Bordetella pertussis toxin concurrently with immunization abrogated its resistance, enhanced Ag-specific IFN-gamma production in culture, and yielded a primed cell population capable of transferring EAU. Conversely, immunization of Lewis rats with R16 in IFA induced little or no disease; the primed cells produced minimal amounts of IFN-gamma and did not transfer EAU. However, addition of IL-12 into the culture resulted in a highly pathogenic, IFN-gamma-producing cell population. We conclude that genetic susceptibility to ocular autoimmunity in this model is connected to an elevated Th1 response. Genetic resistance, however, does not seem to involve an elevated Th2 response, but rather an inhibited development of Th1-like effector cells.

Amino Acid Sequence↗

Uveitogenic T lymphocytes in the rat: pathogenicity vs. lymphokine production, adhesion molecules and surface antigen expression.

A possible correlation between the pathogenicity of autoimmune T cells and their lymphokine production, expression of functional adhesion molecules and expression of some surface antigens was examined. We used four retinal antigen-specific Lewis rat T cell lines and sublines: one specific to the major pathogenic epitope of the human retinal soluble antigen (S-Ag; residues 337-356), and three specific to the major pathogenic epitope of the bovine interphotoreceptor retinoid binding protein (IRBP; residues 1177-1191). The lines have different degrees of uveitogenicity, from highly pathogenic to nonpathogenic. All four T cell lines produced roughly equivalent amounts of interferon-gamma, lymphotoxin/tumor necrosis factor (TNF alpha/beta), interleukin-3, interleukin-6 and transforming growth factor-beta. Interleukin-4 activity could not be detected. The lines also expressed similar levels of functional adhesion molecules, as measured by binding to cultured rat aorta endothelial cells. The nonpathogenic subline, however, was the lowest responder to antigenic stimulation with respect to proliferation and interleukin-2 production. Examination of cell surface antigens showed that in contrast to the other lines, the majority of cells in the nonpathogenic subline lacked detectable expression of CD4. No difference was found in the level of expression of the IL-2 receptor and T cell antigen receptor among the four lines. Because CD4 is the restricting element in these lines, reduced CD4 expression in the nonpathogenic subline may at least partially explain its poor response in vitro to antigenic stimulation. All three attributes could be connected to lack of pathogenicity of this line in vivo. These results support the contention that class II-restricted recognition of autoantigen within the neuroretina by uveitogenic T lymphocytes must occur as an initial step in the pathogenesis of EAU. A defect in this step will preclude pathogenesis regardless of some other functional attributes possessed by effector T cells, such as production of inflammatory lymphokines and expression of adhesion molecules.

Animals↗

[Autoimmune hemolytic anemia with cold antibodies and hemoglobinuria secondary to EBV infection].

The infection caused by EBV can be followed by immunological complications. One of these is autoimmune hemolytic anemia that up to today has been observed during infective mononucleosis only a few times. The authors describe a patient with this rare complication of the EBV infection and discuss its main clinical, pathogenetic and laboratory aspects, with particular attention to the presence of hemoglobinuria and to the absence of anti-i-antibodies. The disease's evolution was spontaneously favorable. For this reason and for the possible risks secondary to transfusions and to other therapeutical interventions, the authors believe that in autoimmune hemolytic anemia a vigil wait is more opportune before beginning the therapy.

Anemia, Hemolytic, Autoimmune↗

Genetic factors in susceptibility and resistance to experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) can be induced in susceptible stains of rats and mice by immunization with purified retinal antigens, and serves as a model for human uveitis. Because strong HLA associations have been noted in a number of human uveitic diseases, we investigated the role of major histocompatibility complex (MHC) vs. non-MHC genes in the control of susceptibility to ocular autoimmunity, using the mouse and the rat EAU models. It was shown that EAU expression in mice requires both a susceptible MHC haplotype and a "permissive" genetic background. MHC control of susceptibility was tentatively mapped to the I-A subregion in H-2k. I-Ek expression appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine "permissiveness" or "nonpermissiveness" of a particular genetic background, as studied in mice and rats, may include diverse genetic mechanisms spanning regulation of cytokines, hormones, vascular effects and the T cell repertoire. Taken together, the data suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background.

Animals↗

Effects of almitrine bismesylate on nocturnal hypoxemia in patients with chronic bronchitis and obesity.

In a double-blind placebo controlled randomised study, the effects of almitrine bismesylate on the sleep induced Hb desaturations, associated or not with disorders of breathing, were tested. Patients (37-75 yrs, 8M and 2F) were affected by chronic bronchitis (out of any exacerbation) and obesity (weight excess at least 20%). They were known to have at least one nocturnal episode of hypoxemia (SaO2 fall higher or equal to 10%) with respect to the wakefulness level. Patients received either placebo or almitrine (1.5 mg/Kg/day) for 18 days and nocturnal polysomnography was performed both before and the last day of treatment. Almitrine induced an increase in PaO2 during wakefulness (p less than .05), an increase in mean SaO2 during sleep (p less than .01) and a decrease in the quantity of desaturation (Qd) during sleep, defined as the product of the mean desaturation by the duration of the episodes of desaturation (p less than .025). No clear effect could be observed either on the mean duration of the sleep disordered breathing (SDB) events or on their frequency whereas the desaturations due to them had a decrease.

Adult↗

Applicability of a simple nasal provocation test in etiologic diagnosis of bronchial asthma.

The applicability of nasal challenge for etiologic diagnosis of extrinsic asthma was evaluated by assessing easiness of performance, precision, and cost of a standardized test by metered nebulizer in 20 asthmatics with and without concurrent rhinitis submitted also to skin prick tests and RAST. Although less sensitive than in the group with rhinitis (where precision was 90.4%), the nasal provocation test proved to be an easy, inexpensive, and specific (82.3%) means for contributing to the identification of allergic sensitization in patients affected by asthma alone.

Administration, Intranasal↗

Variability of peak expiratory flow rate as a prognostic index in asymptomatic asthma.

The prognostic relevance of an enhanced variability of peak expiratory flow rate (PEFR) throughout the day was evaluated in asthmatics in remission: it was expressed as the coefficient of variation (CV) of values recorded 4 times daily for 2 weeks. Outcome at 3, 6, and 12 months was assessed in 2 groups of 16 patients each, differing because of a CV respectively higher (group A) and lower (group B) than 8%. A significantly higher frequency of abnormal PEFR values during the subsequent 3 months was recorded in patients of group A, and found as correlated to the magnitude of CV; in the same group a significantly worse clinical status--scored on the basis of response to treatment--was pointed out. Therefore, a high CV of PEFR may be assumed as a reliable indicator of the risk of exacerbation--not otherwise predictable--both in a short and a longer term; on this basis home monitoring of PEFR may be recommended as a useful tool in the evaluation of all the cases of asthma in remission.

Adolescent↗