Biomedical subjects

John Brennan

Publications and source records attributed to John Brennan.

11 recordsLinked to original sources

PubMed2006

Progressive grey matter atrophy over the first 2-3 years of illness in first-episode schizophrenia: a tensor-based morphometry study.

Little is known about the structural brain changes that occur over the first few years of schizophrenia, or how these changes differ from those associated with healthy brain development in adolescence and early adulthood. In this study, we aimed to identify regional differences in grey matter (GM) volume between patients with first-episode schizophrenia (FES) and matched healthy controls, both at the time of the patients' first psychotic episode (baseline condition) and 2-3 years subsequently (follow-up condition). Forty-one patients with FES and 47 matched healthy controls underwent a T1-weighted structural MRI scan. Of these participants, 25 FES patients and 26 controls returned 2-3 years later for a follow-up scan. Voxel-based morphometry in SPM2 was used to identify the regions of GM difference between the groups in the baseline condition, while tensor-based morphometry was used to identify the longitudinal change within subject over the follow-up interval. The FES patients exhibited widespread GM reductions in the frontal, parietal, and temporal cortices and cerebellum in the baseline condition, as well as more circumscribed regions of GM increase, particularly in the occipital lobe. Furthermore, the FES subjects were observed to lose considerably more GM over the follow-up interval than the controls, especially in the parietal and temporal cortices. We argue that the progressive GM atrophy we have found to be associated with the onset of schizophrenia arises from a dysfunction in the dramatic period of healthy brain development typically associated with adolescence.

Adolescent↗

PubMed2005

Induction of high levels of protective immunity in mice after vaccination using dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis.

Adoptively transferred dendritic cells presenting antigens derived from different pathogens have been shown to elicit specific T cell responses and to induce protective antibacterial immunity. We describe here the induction of high levels of protective immunity in mice using dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis. We provide evidence that protection is superior to BCG and that it is associated with increased priming of CD4+ and CD8+ T cells specific for mycobacterial antigens. This method for generating high levels of anti-bacterial protective immunity could be helpful in the design of novel vaccines against tuberculosis and other intracellular pathogens.

Adoptive Transfer↗

PubMed2005

Grey matter deficits and symptom profile in first episode schizophrenia.

Several studies have investigated grey matter reductions in first episode schizophrenia (FES), but few have examined the relationship between grey matter reduction and clinical profile. A group of 31 patients with strictly defined FES and 30 healthy controls underwent T1-weighted magnetic resonance imaging (MRI) scan. Voxel-based morphometry in SPM99 was used to identify four distinct regions of grey matter reduction in the FES subjects. The regions of interest (ROIs) were in the left ventral prefrontal cortex (ROI 1), left parietal and temporal cortices (ROI 2), right cerebellum (ROI 3), and right frontal and parietal cortices (ROI 4). These regions of reduction were transformed into binary masks, which were convolved with patients' pre-processed grey matter images. Patients' grey matter volumes in these regions were correlated with their composite scores on the following three symptom dimensions: Psychomotor Poverty, Disorganization and Reality Distortion. The volumes of ROIs 1, 2 and 4 were found to be significantly correlated with the Reality Distortion syndrome score. Our findings indicate that distinct, widespread grey matter reductions are present very early in the course of schizophrenia. The results also suggest a possible structural underpinning for the abnormal brain activity typically associated with symptoms of Reality Distortion.

Adult↗

PubMed2005

Unrecognized pylephlebitis causing life-threatening septic shock: a case report.

A man who developed profound septic shock was treated for Escherichia coli sepsis of unknown origin. Following stabilisation, a diagnosis of pylephlebitis (infection and thrombosis in the portal vein) was made at computed tomography. A review of the condition, its primary causes, typical features, investigation and management was presented.

Aged↗

PubMed2005

Relative contributions of psychiatric symptoms and neuropsychological functioning to quality of life in first-episode psychosis.

OBJECTIVE: To report on the relationship between quality of life (QOL), psychiatric symptoms and neuropsychological functioning in a sample of young people who have experienced a first episode of psychosis 2-3 years following initial presentation. METHOD: Fifty-one participants aged 15-27 years old completed the short form of the World Health Organization Quality of Life scale (WHOQOL-Bref), a self-report instrument assessing physical, psychological, social and environmental aspects of QOL. A comprehensive neuropsychological battery was administered. Measures of psychiatric symptoms including depression (as assessed by the Calgary Depression Scale), positive, negative and general psychopathology (as assessed by the Positive and Negative Syndrome Scale) were obtained. RESULTS: Multiple regression analyses were used to evaluate the ability of neuropsychological measures and psychiatric symptoms to predict QOL. When neuropsychological variables were considered on their own, cognitive flexibility, verbal fluency, verbal ability and sustained attention explained up to 28% of the variance in the four domains of QOL. However, in the presence of psychiatric symptoms, neuropsychological variables were no longer significant predictors for physical and psychological QOL; depression, general psychopathology and negative symptoms together explained up to 43% of the variance in QOL, with neuropsychological variables remaining significant for social and environmental QOL. CONCLUSIONS: In young people with their first episode of psychosis, QOL is more strongly related to levels of psychopathology, particularly depression, than neuropsychological deficits. This finding replicates previous studies in chronic schizophrenia that have suggested QOL is more strongly related to levels of psychopathology than the presence of neuropsychological deficits.

Adult↗

PubMed2005

Therapeutic efficacy of high-dose intravenous immunoglobulin in Mycobacterium tuberculosis infection in mice.

Intravenous immunoglobulin (IVIg) is used to treat patients with primary antibody deficiencies and, at high doses, to treat a range of autoimmune and inflammatory disorders. With high-dose IVIg (hdIVIg), immunomodulatory mechanisms act on a range of cells, including T cells, B cells, and dendritic cells. Here, we demonstrate that the treatment of M. tuberculosis-infected mice with a single cycle of hdIVIg resulted in substantially reduced bacterial loads in the spleen and lungs when administered at either an early or late stage of infection. Titration of the IVIg showed a clear dose-response effect. There was no reduction in bacterial load when mice were given equimolar doses of another human protein, human serum albumin, or maltose, the stabilizing agent in the IVIg preparation. HdIVIg in vitro had no inhibitory effect on the growth of M. tuberculosis in murine bone marrow-derived macrophages. In addition, the effect of hdIVIg on bacterial loads was not observed in nude mice, suggesting the involvement of conventional T cells. Analysis of T cells infiltrating the lungs revealed only small increases in CD8(+) but not CD4(+) T-cell numbers in hdIVIg-treated mice. The mechanism of action of hdIVIg against tuberculosis in mice remains to be determined. Nevertheless, since hdIVIg is already widely used clinically, the magnitude and long duration of the therapeutic effect seen here suggest that IVIg, or components of it, may find ready application as an adjunct to therapy of human tuberculosis.

Animals↗

PubMed2004

Neuropsychological correlates of symptom profiles in first episode schizophrenia.

This paper aimed to examine the relationship between the trichotomous symptom structure of psychopathology and neuropsychological functioning in young people with first episode schizophrenia (FES), most of whom were receiving atypical antipsychotic medication. This was with a view to providing insight into the underlying pathophysiology of the clinical symptoms of schizophrenia. Fifty-three young people (aged 13-25 years) with FES participated in the study. Subjects completed a comprehensive clinical and neuropsychological examination. Cognitive domain scores were correlated with composite scores relating to Disorganisation, Psychomotor Poverty and Reality Distortion. A significant association was identified between Disorganisation and Verbal Acquisition, Verbal Recall and Cognitive Flexibility. There were no significant associations between cognitive domains and either Reality Distortion or Psychomotor Poverty, nor with measures of depressive symptomatology. The present study provides preliminary evidence that symptoms associated with the Disorganisation factor are significantly associated with cognitive deficits suggesting impaired frontal-temporal functioning. Differences between the current findings and those of similar research may reflect the effects of different medication regimes, as well as the absence of illness chronicity.

Adolescent↗

PubMed2004

Cognitive functioning in young people with first episode psychosis: relationship to diagnosis and clinical characteristics.

OBJECTIVE: To examine the extent and nature of neuropsychological deficits in adolescents and young people with first episode psychosis (FEP), and to determine whether the pattern and extent of neuropsychological deficits varied according to diagnosis. METHOD: A total of 83 FEP subjects aged 13-25 years, and 31 healthy controls completed a comprehensive battery of neuropsychological tests, grouped into 10 cognitive domains. First episode psychosis subjects were stratified into three diagnostic groups (schizophrenia, affective disorders, substance-induced psychosis) and differences in cognitive profiles were examined. The contribution of demographic and clinical characteristics to cognitive performance was also explored. RESULTS: The schizophrenia group demonstrated significantly worse performance on tasks of verbal learning and memory than the affective disorders group. Compared to healthy controls, the schizophrenia group also demonstrated global impairment across the majority of cognitive domains. The substance-induced group's performance lay between that of the schizophrenia and affective disorders groups. Analyses of differential deficits revealed that verbal learning, verbal memory and current intellectual functioning were selectively impaired in the schizophrenia group, whereas the affective disorders group demonstrated a selective deficit in speeded processing. Premorbid intellectual functioning, negative symptomatology and medication levels were the strongest predictors of cognitive performance in FEP subjects. CONCLUSIONS: Verbal memory deficits differentiate individuals with schizophrenia from those with psychotic affective disorders. Although significant cognitive deficits are evident across all diagnostic FEP groups, individuals with schizophrenia appear to have more generalized impairment across a broad array of cognitive functions than other psychotic diagnoses. Lower premorbid intellectual functioning does not appear to contribute to greater cognitive deterioration following onset of psychosis, but severity of illness may be a more important factor than levels of mood disturbance.

Adolescent↗

PubMed2002

Aneurysm neck diameter after endovascular repair of abdominal aortic aneurysms.

PURPOSE: To determine aneurysm neck diameter change after endovascular repair (EVR) of abdominal aortic aneurysm (AAA) and its relationship to stent-graft diameter. MATERIALS AND METHODS: The cases of 73 patients with AAAs who underwent EVR were reviewed retrospectively: 68 had preoperative imaging available. Neck diameter was reviewed by a single observer (M.F.B.) on preoperative, immediate postoperative, annual, and most recent contrast-enhanced computed tomographic scans. Baseline and follow-up neck diameters were compared with the manufacturers' values for unconstrained stent-graft diameters. RESULTS: Intraobserver error was 2 mm. Aneurysm neck diameter increased from 21.8 mm (range, 17-28 mm) at baseline to 22.8 mm (range, 19-30 mm) postoperatively and 25.8 mm (range, 19-31 mm; P <.001) at a mean follow-up of 25.5 months (range, 6.2-60.8 mo). Neck diameter increase was more than 2 mm in 24 patients (33%). Mean change in the first, second, third, and fourth years was +1.63 mm, +0.52 mm, +0.25 mm, and +0.33 mm, respectively. Baseline mean stent-graft oversizing was 2.9 mm (13.7%; range, -1 to +8 mm), which decreased to 0.7 mm (range, -4 to +6 mm) at latest follow-up. Neck diameter exceeded stent-graft diameter (mean, 1.8 mm; range, 1-4 mm) in 21 cases (28%) and by more than 2 mm in five cases (6.8%). When neck diameter change was correlated with change in sac diameter, it was found to be insignificant (P =.24); however, it was significantly correlated with baseline oversizing (P =.01). CONCLUSIONS: After EVR, the aneurysm neck dilates, mostly in the first 2 years, by greater than 2 mm in one third of patients. This is possibly related to the presence of the endograft. The associated reduction of stent-graft oversizing warrants continued vigilance for proximal endoleak.

Aged↗

PubMed2002

Detection of endoleak with enhanced ultrasound imaging: comparison with biphasic computed tomography.

PURPOSE: To compare unenhanced and enhanced ultrasound imaging to biphasic computed tomography (CT) in the detection of endoleak after endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Fifty-three patients (44 men; mean age 70 years) were examined during 96 follow-up visits after endovascular AAA repair. All patients had color Doppler and power Doppler ultrasound studies performed before and after the administration of an ultrasound contrast agent. Biphasic (arterial and delayed) CT was performed on the same day, and the ultrasound and CT studies were independently scored to record the presence or absence of endoleak and the level of confidence in the observation. RESULTS: The sensitivity of the ultrasound techniques to detect endoleak improved with the use of ultrasound contrast media, ranging from a low of 12% with unenhanced color Doppler to 50% with enhanced power Doppler. However, the enhanced power Doppler failed to detect 9 type II endoleaks identified by CT (86% negative predictive value for endoleak). There were only 2 graft-related endoleaks in the study; one was diagnosed from the ultrasound image, but the other had nondiagnostic ultrasound scans because of poor views. CONCLUSIONS: Ultrasound scanning with or without contrast enhancement was not as reliable as CT in diagnosing type II endoleak. CT imaging remains our surveillance modality of choice.

Aged↗

PubMedDate not supplied

Clinical profiles, scope and general findings of the Western Sydney First Episode Psychosis Project.

OBJECTIVE: To examine the clinical profile, treatment and social functioning of a community-based sample of young people presenting with their first episode of psychosis. METHODS: Over a 2-year period, young people with their first episode of psychosis referred to early intervention services in two area mental health services in western Sydney were assessed with a battery of clinical, neuropsychological, psychophysiological and neuroanatomical measures. This paper reports the clinical results of the baseline section of the study. RESULTS: Of the 224 referrals to the project, 94 subjects meet inclusion criteria and agreed to take part. Subjects were divided into three diagnostic groups--'Schizophrenia', 'Mood Disorders' and 'Mixed Psychosis', the latter principally comprised of substance induced psychotic disorders. Subjects from the 'Schizophrenia' group differed significantly from the other two groups in that they had higher levels of negative symptoms and general psychopathology, and were less likely to be employed or engaged in study. They had poorer overall social functioning. Subjects with 'Mixed Psychosis' were similar to those from the 'Schizophrenia' group in that they were older and male, but they did not have the same burden of negative symptoms as the 'Schizophrenia' group. The 'Mood Disorders' group was younger, female and had overall a higher level of psychosocial functioning than the other two groups. Subjects from the 'Mood Disorders' group were more likely to be managed with mood stabilisers and multiple drug therapies. The use of atypical antipsychotic medication was almost universal. CONCLUSIONS: Even shortly after the time of presentation to mental health services young people with a schizophrenia spectrum diagnosis have a heavier burden of symptoms and are significantly more impaired by them than young people with other psychotic illnesses. This and their symptom profile differentiated them from young people with other psychotic disorders.

Activities of Daily Living↗