Biomedical subjects

B F O'Donnell

Publications and source records attributed to B F O'Donnell.

At least 19 recordsLinked to original sources

PubMed1999

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.

Brain Mapping↗

PubMed1999

Human leucocyte antigen class II associations in chronic idiopathic urticaria.

The major histocompatibility complex (MHC) acts as a marker for self during T-cell ontogeny and is associated with the pathogenesis of many autoimmune diseases. Recent investigations have shown about 30% of patients with chronic idiopathic urticaria (CIU) have IgG autoantibodies against the high-affinity IgE receptor, FcepsilonRI, or IgE. A link between MHC class II alleles and CIU has not been reported previously. DNA was extracted from blood of 100 Caucasian patients with CIU, and the MHC class II type determined using the polymerase chain reaction with sequence-specific primers, testing for DRB and DQB1 alleles. The frequency of alleles in CIU patients was compared with that found in 603 controls. Further human leucocyte antigen (HLA) typing on patient subsets, classified by the patients' responses to intradermal injection of autologous serum and their serum-induced histamine release from basophil leucocytes of healthy donors, was undertaken. HLA DRB1*04 (DR4) and its associated allele, DQB1*0302 (DQ8), are raised in CIU patients compared with a control population (P = 2 x 10-5 and P = 2 x 10-4, respectively). HLA DRB1*15 (DR15) and its associated allele, DQB1*06 (DQ6), are significantly less frequently associated with CIU. The HLA DRB1*04 association is particularly strong (corrected P = 3.6 x 10-6) for patients whose serum has in vivo and in vitro histamine-releasing activity. HLA class II typing is consistent with the concept that CIU is a heterogeneous disease, and supports an autoimmune pathogenesis in a subset of patients.

Adolescent↗

PubMed1998

High-density recording and topographic analysis of the auditory oddball event-related potential in patients with schizophrenia.

BACKGROUND: Prior research has shown reductions of the N1, N2, and P300 auditory event-related potential (ERP) components in schizophrenic patients. Most studies have shown a greater P300 reduction in left versus right temporal leads in schizophrenic patients. These studies were done with sparse electrode arrays, covering restricted areas of the head, thus providing an incomplete representation of the topographic field distribution. METHODS: We used a 64-channel montage to acquire auditory oddball ERPs from 24 schizophrenic patients and 24 controls subjects. The N1, P2, N2, P300, and N2 difference (N2d) amplitudes and latencies were tested for group and laterality differences. Component topographies were mapped onto a three-dimensional head model to display the group differences. RESULTS: The schizophrenic group showed reduction of the N1 component, perhaps reflecting reduced arousal or vigilance, but no N1 topographic difference. An N2d was not apparent in the schizophrenic patients, perhaps reflecting severe disruption in neural systems of stimulus categorization. In the patients, the P300 was smaller over the left temporal lobe sites than the right. CONCLUSIONS: The increased ERP spatial sampling allowed a more complete representation of the dipolar nature of the P300, which showed field contours consistent with neural sources in the posterior superior temporal plane.

Adult↗

PubMed1998

A neuropsychological analysis of schizophrenic thought disorder.

We examined the relationship of schizophrenic thought disorder, as measured by the Thought Disorder Index (TDI), with (1) neuropsychological measures of verbal memory, abstraction, executive function, visual memory, and working memory; and (2) quantitative MRI measures of prefrontal and basal ganglia structures. TDI scores correlated strongly with tests of verbal memory, abstraction and executive functions, modestly with tests of working memory, but did not correlate with scores on tests of visual memory. Neither TDI scores nor their neuropsychological correlates were associated with frontal or basal ganglia magnetic resonance imaging (MRI) measures, with the exception of the measures of working memory that demonstrated a modest relationship with frontal and basal ganglia structures. These findings suggest that schizophrenic thought disorder may be strongly related to neuropsychological impairments in verbal memory, abstraction and executive functions, and modestly related to problems with working memory in this sample of patients.

Adult↗

PubMed1998

Intravenous immunoglobulin in autoimmune chronic urticaria.

Histamine releasing autoantibodies play a central role in the pathogenesis of chronic urticaria (CU) in approximately 30% of affected patients. We investigated the therapeutic effect of high-dose intravenous immunoglobulin (IVIG) on disease activity in patients with severe CU of autoimmune aetiology. Autoimmune urticaria was diagnosed by the development of a weal-and-flare reaction to the intradermal injection of autologous serum and by serum-induced histamine release from the basophil leucocytes of healthy donors in vitro. Ten patients with severe, autoimmune CU, poorly responsive to conventional treatment, were treated with IVIG 0.4 g/kg per day for 5 days. The outcome on cutaneous wealing and itch was monitored using urticaria activity scores, visual analogue scales and autologous intradermal serum tests. Clinical benefit was noted in nine of 10 patients: three patients continue in prolonged complete remissions (3 years follow-up), two had temporary complete remissions, and symptoms in four patients improved subsequent to treatment. There was significant improvement in the urticaria activity scores and visual analogue scores at 2 (P < 0.01) and 6 weeks (P < 0.01) post-IVIG compared with the baseline values (Wilcoxon matched pairs). The diminution in urticarial activity in the majority of patients corresponded with a reduced weal-and-flare response to the intradermal injection of autologous post-treatment serum compared with the pretreatment serum. Minor side-effects were common, but there were no serious or long-term adverse effects. IVIG represents a novel therapeutic option in selected patients with recalcitrant CU associated with histamine releasing autoantibodies.

Adult↗

PubMed1998

Not all chronic urticaria is "idiopathic"!

The aetiology of chronic urticaria in the majority of patients is elusive. The cause of physical urticarias (dermographism, delayed pressure urticaria, cold urticaria) is unknown. We have identified a subset of chronic "idiopathic" urticaria patients, representing approximately 30% of the total in which the disease is caused by the presence of IgG autoantibodies against the high affinity IgE receptor (FcepsilonRIalpha). This functional autoantibody stimulates normal (albeit vicarious) activation of mast cells and basophils via FcepsilonRI, causing whealing and angioedema. Anti-FcepsilonRI-positive patients are recognized by a combination of autologous serum skin testing and evoked histamine release from basophils of normal human donors. Autoantibody-positive and -negative patients are clinically indistinguishable and are treated routinely by combinations of H1 and occasionally H2-antihistamines in both cases. However, severely affected patients who are anti-FcepsilonRI-positive can also be treated by non-specific immunotherapy (plasma pheresis, intravenous immunoglobulin, cyclosporin.

Autoantibodies↗

PubMed1998

Word recall in schizophrenia: a connectionist model.

OBJECTIVE: The authors examined word recall of patients with schizophrenia by using an experimental paradigm generated from connectionist models of memory. METHOD: Schizophrenic patients and normal comparison subjects first studied and then recalled a list of 32 words of equal difficulty. Both the connectivity (associative strength) and the network size (number of associates) of the words varied in such a way that the list contained equal proportions of four types of words: 1) high connectivity-small network size, 2) low connectivity-small network size, 3) high connectivity-large network size, and 4) low connectivity-large network size. RESULTS: The schizophrenic patients recalled fewer words and showed a particularly pronounced effect of the connectivity of the to-be-remembered words. For the patients, regardless of network size, recall improved substantially for words of high connectivity and declined dramatically for words of low connectivity. By contrast, the comparison subjects showed the expected effects, with the best recall for words of high connectivity-small network size, followed by words of low connectivity-small network size, then by words of high connectivity-large network size, and finally by words of low connectivity-large network size. CONCLUSIONS: Schizophrenia may be characterized by faulty modulation of associative links within a putative lexicon that is thought to be widely distributed across frontal and temporal lobes.

Adult↗

PubMed1998

Auditory mismatch negativity in schizophrenia: topographic evaluation with a high-density recording montage.

OBJECTIVE: The mismatch negativity, a negative component in the auditory event-related potential, is thought to index automatic processes involved in sensory or echoic memory. The authors' goal in this study was to examine the topography of auditory mismatch negativity in schizophrenia with a high-density, 64-channel recording montage. METHOD: Mismatch negativity topography was evaluated in 23 right-handed male patients with schizophrenia who were receiving medication and in 23 nonschizophrenic comparison subjects who were matched in age, handedness, and parental socioeconomic status. The Positive and Negative Syndrome Scale was used to measure psychiatric symptoms. RESULTS: Mismatch negativity amplitude was reduced in the patients with schizophrenia. They showed a greater left-less-than-right asymmetry than comparison subjects at homotopic electrode pairs near the parietotemporal junction. There were correlations between mismatch negativity amplitude and hallucinations at left frontal electrodes and between mismatch negativity amplitude and passive-apathetic social withdrawal at left and right frontal electrodes. CONCLUSIONS: Mismatch negativity was reduced in schizophrenia, especially in the left hemisphere. This finding is consistent with abnormalities of primary or adjacent auditory cortex involved in auditory sensory or echoic memory.

Acoustic Stimulation↗

PubMed1998

Delayed recall in dementia: sensitivity and specificity in patients with higher than average general intellectual abilities.

OBJECTIVE: Distinguishing early dementia from normal aging is especially difficult in patients with higher than average intellectual abilities. To find signs useful in determining that the elderly "worried and well" are not in an early phase of dementia, we compared the neuropsychological test performance of demented patients, patients who were not found to be demented, and control subjects. METHOD: A retrospective study of neuropsychological test results from persons over 50 years of age who had an age-adjusted verbal intelligence quotient (VIQ) greater than or equal to 110. Analysis of covariance (using age and education as covariates) was used to compare the normal, no dementia, and dementia groups. Significant differences were further analyzed using Tukey's post hoc procedure. Tests on which the three groups differed at ap < 0.01 level were included in multivariate analyses. RESULTS: The no dementia patient group performed at functional levels comparable to those of the control group. By contrast, patients with dementia showed significant impairment on tests of memory, naming, and visuospatial function compared with both the control and no dementia groups. Immediate and delayed paragraph recall classified groups with a 96% specificity and 80% sensitivity in the multivariate discriminant analysis. CONCLUSIONS: These results suggest that in patients with higher than average intelligence, the absence of a significant dementing process (as well as its presence) can be determined with reasonable probability.

Aged↗

PubMed1997

A topographic study of ERPs elicited by visual feature discrimination.

The functional properties and topographic distribution of event-related potential (ERP) components elicited by visual discrimination of orientation, spatial frequency, spatial location, and color were investigated. ERPs were recorded from 28 electrode sites from 16 adult subjects. Five ERP components were measured: N1 (peak latency = 160 ms), P2 (250 ms), anterior N2 (260 ms), posterior N2 (280 ms), and P3 (400 ms). N1 and P2 were more negative when a stimulus was a target, showing the selection negativity effect. Feature-specific effects on component amplitude or topography varied by component. N1 and P2 were sensitive to stimulus orientation and location. Anterior or posterior N2 was sensitive to orientation, spatial frequency, and location. P3 varied with orientation, but not with other stimulus features. Cross-task comparisons of ERPs to vertical line segments in the color, orientation, and location discrimination tasks indicated that P2 and N2, but not N1 and P3, were sensitive to changes in task-demand. These data provide topographic evidence that ERP components in the 160-400 ms time domain can be differentiated on the basis to processing of specific visual features, and reflect neurophysiologically distinct visual pathways in the human cortex.

Adult↗

PubMed1997

ERP assessment of visual and auditory language processing in schizophrenia.

Language disturbance in schizophrenia has been recently attributed to disturbed priming mechanisms. In the present study, event-related potentials (ERPs), were recorded to final words in sentences presented to 13 chronic patients with schizophrenia and 12 normal controls. Half of the final words fit a sentence context and another half did not. The N400 (the ERP sensitive to language) latency was prolonged, and its amplitude was more negative to both correct and incorrect sentence endings in the group with schizophrenia relative to the group of normal controls. The early ERP components, N100 and P200, were similar in both groups. These results suggest that language abnormalities in schizophrenia are related to a dysfunction in the language system and not to a general cognitive dysfunction, and may be related to poor use of context in patients with schizophrenia.

Adult↗

PubMed1997

Aberrant semantic activation in schizophrenia: a neurophysiological study.

OBJECTIVE: Schizophrenia has long been thought to be characterized by a fundamental disturbance in semantic associations, which has often been presumed to be of neurobiological origin. The authors examined the neurophysiological characteristics of semantic processing in schizophrenic patients. METHOD: During EEG recording, 15 schizophrenic patients and 15 age-matched comparison subjects read sentences that had either sensible or nonsensical endings. The authors recorded the N400 component, a specific negative event-related brain potential occurring approximately 400 msec after the final word in the sentence. N400 is highly, if not uniquely, sensitive to semantic expectancy and context, and larger, more negative N400 amplitude is associated with increased semantic unexpectancy. RESULTS: In relation to the normal comparison subjects, the schizophrenic patients demonstrated prolonged N400 latency after nonsensical sentence endings and also showed enhanced N400 negativity, regardless of the sense of the sentence ending. CONCLUSIONS: These findings suggest slower and more diffuse semantic activation in patients with schizophrenia, perhaps reflective of a disease-related failure to maintain and to use semantic context.

Adult↗

PubMed1997

The impact of chronic urticaria on the quality of life.

The impact of chronic urticaria (CU) on the quality of life is undocumented. We assessed quality of life in patients with CU, including patients with associated delayed pressure urticaria (DPU). One hundred and forty-two out-patients completed self-administered questionnaires: a disease-specific, purpose designed questionnaire, and the Nottingham health profile (NHP). Many patients reported problems attributable to their skin condition in facets of everyday life including home management, personal care, recreation and social interaction, mobility, emotional factors, sleep, rest and work. The NHP part I scores showed restriction in the areas of mobility, sleep, energy, and demonstrated pain, social isolation and altered emotional reactions. Part II of the NHP showed that patients experienced difficulties in relation to work, looking after the home, social life, home relationships, sex life, hobbies and holidays. The patients with DPU had significantly more problems with mobility, gardening and choice of clothing than the uncomplicated CU patients. They also suffered more pain, had more problems with work and were more restricted in their hobbies.

Activities of Daily Living↗

PubMed1996

Does palpability of primary cutaneous melanoma predict dermal invasion?

BACKGROUND: Relatively few studies have addressed the question of whether clinical estimation of melanoma thickness by palpation can accurately predict its histologic thickness. If palpability was a reliable predictor of dermal invasion, it could be used to define the surgical margin. OBJECTIVE: We sought to determine whether clinical elevation of melanoma could be used to predict the presence or absence and the degree of dermal invasion in patients with stage 1 cutaneous melanoma. METHODS: Melanomas in 165 patients were categorized by one observer as flat, just palpable, palpable, or nodular. This was compared with histologic measurements of tumor thickness. RESULTS: Overall there was significant correlation between the degree of palpability of melanoma and the presence or absence of dermal invasion (p<0.001), Breslow thickness (p<0.0001), and Clark level (p<0.001). However, the relation between palpability and Breslow thickness for invasive melanomas less than 1 mm thick was weaker (n=62, p=0.053), and the correlation between elevation and Clark level was not significant for invasive melanomas less than 4 mm thick (n=111, p>0.999). CONCLUSION: We conclude that palpability of melanoma is an inadequate guide to the presence or absence and degree of dermal invasion in melanomas less than 1 mm thick and cannot be used to determine the surgical margin.

Adolescent↗

PubMed1996

Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria.

Previous studies identified autoantibodies against the IgE high affinity receptor alpha-chain, Fc epsilon RI alpha, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-Fc epsilon RI alpha autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti-Fc epsilon RI alpha autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4-34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG-mediated. Preincubation of sera or the IgG fraction with a recombinant alpha-chain of Fc epsilon RI inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-Fc epsilon RI alpha autoantibodies mediate histamine release from skin mast cells in vitro and, taken together with in vivo evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-Fc epsilon RI alpha autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.

Adolescent↗

PubMed1996

Correlations of premorbid adjustment in schizophrenia with auditory event-related potential and neuropsychological abnormalities.

OBJECTIVE: The authors examined the relationship between premorbid adjustment in schizophrenia and event-related potential data and neuropsychological data obtained after onset of the illness. METHOD: They interviewed 13 male veterans with chronic schizophrenia, 12 normal comparison subjects, and their first-degree relatives and also obtained objective data from the patients' school records and charts. They used interview and objective data to score the Cannon-Spoor Premorbid Adjustment Scale. Patients and comparison subjects were also given event-related potential tests, the Wisconsin Card Sorting Test, and the Wechsler Memory Scale-Revised. RESULTS: Worse premorbid adjustment in the schizophrenic patients was significantly associated with a marked reduction of the N2 component amplitude of the auditory event-related potential measured over the left temporal and central regions, but it was not associated with the P3 component amplitude. Worse Premorbid Adjustment Scale scores were significantly associated with more perseverative errors on the Wisconsin Card Sorting Test and worse performance on the visual memory span task of the Wechsler Memory Scale. CONCLUSIONS: Premorbid adjustment may predict the severity of specific neurophysiological and neuropsychological abnormalities in schizophrenia.

Adult↗

PubMed1996

Selective deficits in visual perception and recognition in schizophrenia.

OBJECTIVE: The purpose of this study was to evaluate the performance of patients with schizophrenia on tests of visual discrimination and recognition of different stimulus features. METHOD: Thirteen medicated male schizophrenic patients and 13 normal comparison subjects were tested on four stimulus features: spatial frequency, pattern, location, and trajectory. Subjects had to make both discrimination and recognition judgments at three levels of stimulus disparity. RESULTS: The responses of the patient group were slower and less accurate than those of the comparison group on both the discrimination and recognition tasks. The patients were less accurate than the comparison subjects in processing spatial features of the stimuli, particularly trajectory, but were unimpaired in processing form attributes (high spatial frequencies and patterns). When the results of pattern and trajectory tasks were matched against the accuracy performance of the comparison group, the patients were less accurate on trajectory than on pattern judgments and less accurate on recognition than on discrimination performance. CONCLUSIONS: Schizophrenia may be accompanied by impaired visual spatial perception and representation. In schizophrenia, deficits in trajectory discrimination may reflect a disturbance of the dorsal pathway of the visual system, while disturbances of trajectory recognition performance may reflect a deficit in prefrontal systems involved in visual working memory operations.

Adult↗

PubMed1996

Rate of progression in familial Alzheimer's disease.

The clinical course of early-onset, dominantly inherited, familial Alzheimer's disease (FAD) was contrasted with late-onset, sporadic Alzheimer's disease (AD). Eight FAD and 23 sporadic AD patients were followed over a mean of 63 months from estimated disease onset. The two groups did not differ notably in duration of symptoms from onset, global disease severity, or degree of cognitive deficits on initial evaluation. The Kaplan-Meier lifetable method was used to assess time from estimated disease onset to dependence in self-care, institutionalization, and death. A greater percentage of FAD patients became dependent in self-care and died earlier than did sporadic AD patients. The lifetable results suggest that FAD may have a more rapid course than dose late-onset sporadic AD.

Activities of Daily Living↗