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Biomedical subjects

P B Ward

Publications and source records attributed to P B Ward.

At least 19 recordsLinked to original sources
PubMed2005

Low-level vancomycin resistance in Staphylococcus aureus--an Australian perspective.

Low-level vancomycin resistance in Staphylococcus aureus has emerged as a clinical problem over the past 8 years. The clinical relevance of this resistance has been questioned, and laboratory detection remains difficult and time consuming. There is, however, increasing evidence linking low-level vancomycin resistance with glycopeptide treatment failure in serious Staphylococcus aureus infections. Diagnostic laboratories and clinicians need to be aware of this resistance phenotype, to have procedures in place to detect the resistance, and to have strategies for managing patients with infections caused by resistant strains.

Aged↗
PubMed2002

Disturbed communication in schizophrenia: the role of poor pragmatics and poor mind-reading.

BACKGROUND: Disturbed speech in schizophrenia may reflect pragmatic deficits of expressive language. Pragmatic comprehension deficits also occur in schizophrenia. This study investigated whether poor 'mind-reading' (i.e. a general difficulty with inferring and monitoring other people's thoughts) causes pragmatic language impairments of both expression and comprehension in patients with schizophrenia. METHOD: Mind-reading (or theory of mind) was tested in patients with schizophrenia and in healthy controls using a false-belief picture-sequencing task. Pragmatic comprehension skills were assessed using a test of non-literal speech interpretation. Clinical ratings of formal thought disorder (FTD) indexed the expressive language deficits of patients. To control for possible contributory effects of executive dysfunction, inhibitory control was tested using capture picture-sequences and executive-planning was tested using the Tower of London task. RESULTS: False-belief picture-sequencing, understanding of irony and understanding of metaphors were all selectively impaired in the patients. Poor mind-reading (indexed by high error rate in sequencing false-belief stories) was associated with poor understanding of irony, but was unrelated to poor understanding of metaphors. Whereas poor appreciation of irony and poor mind-reading were associated with high ratings of positive formal thought disorder, high ratings of negative formal thought disorder were associated with poor understanding of metaphors and executive dysfunction. CONCLUSIONS: Whereas poor mind-reading may contribute to positive aspects of formal thought disorder and impaired appreciation of irony in patients with schizophrenia; negative features of formal thought disorder and poor understanding of metaphors appear better explained by abnormal semantics. Overall, the findings of this study support the view that the functional basis of formal thought disorder in schizophrenia is not unitary.

Adolescent↗
PubMed2001

Treatment failure due to methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin.

We report the first instance in Australia of treatment failure due to a strain of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin--heteroresistant vancomycin-intermediate S. aureus (hVISA). The infection occurred in a 41-year-old man with multiple risk factors. No transmission of the organism to other patients or the environment was detected. This case may herald the beginning of a new phase of staphylococcal resistance in Australia.

Adult↗
PubMed2001

Late-onset depression: genetic, vascular and clinical contributions.

BACKGROUND: Neuropsychiatric research needs to examine the relationships between aetiological, genotypic and clinical risk factors and behavioural phenotypes. These relationships can now be examined in older patients with depressive disorders. METHODS: Key behavioural features, clinical and vascular risk factors and putative genotypes for late-onset neurodegenerative disorders and/or vascular disease were recorded in 78 older patients with depression (mean age = 549 years, S.D. = 14.1) and 22 healthy control subjects (mean age = 55.5 years, S.D. = 9.6). RESULTS: Two or more vascular risks were more common in older patients (65% v. 26% of control subjects, P < 0.01), and in patients with late-onset disorders (82% v. 57% in patients with early-onset disorders, P < 0.05). Patients with late-onset depression had a higher prevalence of the homozygous or heterozygous forms of the C677T mutation of the methylenetetrahydrofolate reductase enzyme (MTHFR)(74% v. 48% in patients with early-onset disorders, P < 0.05). In a multivariate model, only presence of the MTHFR gene mutation predicted late-onset depression (odds ratio = 3.8, 95% CI = 1.1-12.9). Neither apolipoprotein E epsilon 4 or epsilon 2 was associated with depression, late-onset depression, cognitive impairment, or psychomotor change. Patients with apolipoprotein E epsilon 4 were less likely to have psychotic forms of depression. CONCLUSIONS: Patients with late-onset depression had an increased rate of the C677T MTHFR gene mutation and other vascular risk factors. This suggests that a proportion of these patients may have genetically-determined and/or other vascular aetiologies. Patients at risk of these disorders may be assisted by currently-available preventative strategies.

Adult↗
PubMed2001

Brachyspira aalborgi infection in four Australian children.

AIM: The clinical presentation of four children and adolescents (two males and two females with a mean age of 12.4 years; range 9-16 years) with colorectal spirochetosis is discussed. RESULTS: Symptoms included persistent diarrhea (n = 2), rectal bleeding (n = 1) and abdominal pain (n = 2). In all patients, colorectal spirochetosis was an unanticipated finding on colonic histology, and the presence of spirochetes was confirmed by the use of electron microscopy. Spirochetes were identified as Brachyspira aalborgi by using PCR amplification of the bacterial 16S rRNA and nicotinamide adenine dinucleotide oxidase sequences in all four patients. No other enteric pathogens were found. CONCLUSIONS: Although all patients appeared to respond to antibiotic treatment, the clinical significance of B. aalborgi as a human pathogen requires further investigation.

Adolescent↗
PubMed2001

Faecal candida and diarrhoea.

BACKGROUND: Candida species are frequently isolated from stools of children with diarrhoea but are not proven enteropathogens. It is hypothesised that faecal candida causes diarrhoea. AIMS: To determine the prevalence of faecal candida in childhood diarrhoea and the relation between faecal yeasts and diarrhoea. METHODS: Comparison of clinical and laboratory data, including quantitative stool culture for yeasts from 107 children hospitalised with diarrhoea and 67 age matched controls without diarrhoea. RESULTS: Yeast species, predominantly candida, were identified in the stools of 43 children (39%) with diarrhoea and 26 (36%) without diarrhoea. The concentration of candida was positively associated with recent antibiotic use (p = 0.03) and with the presence of another enteric pathogen (p < 0.005), but not with patient age, nutritional status, or duration of diarrhoea. CONCLUSION: Candida species do not cause childhood diarrhoea in well nourished children.

Anti-Bacterial Agents↗
PubMed2000

Genetically distinct strains of Candida albicans with elevated secretory proteinase production are associated with diarrhoea in hospitalized children.

BACKGROUND: Candida albicans has been implicated as the aetiological agent in a significant percentage of children with diarrhoea. The virulence properties of C. albicans strains associated with acute and chronic diarrhoea in hospitalized children were investigated. METHODS: The genotypic relationships between the isolates were determined using restriction enzyme analysis and hybridization with a C. albicans-specific DNA probe, 27A. RESULTS AND CONCLUSION: In patients with acute and chronic diarrhoea, there is evidence for selection of specific, genetically distinct strains of C. albicans. Higher levels of secretory Candida acid proteinase produced by isolates from patients with acute diarrhoea may account for the more severe symptoms. However, the lower adherence of these isolates may predispose to the rapid (within 2 to 4 days) resolution of the condition. In patients with chronic diarrhoea the lower levels of proteinase produced correlate with the less severe symptoms, while the increased adherence may account for the persistence of the infection.

Acute Disease↗
PubMed2000

Schizotypy: phenotypic marker as risk factor.

OBJECTIVE: To evaluate measures of schizotypy as familial risk factors for schizophrenia with the aim of making recommendations for assessing schizotypy as part of screening procedures for identifying people at risk of schizophrenia. METHOD: Published studies using self-report and interview-based measures of schizotypy to assess relatives of patients with schizophrenia are reviewed. A parent study is reported evaluating the diagnostic accuracy of parental schizotypy as assessed by three questionnaire-based measures: the Chapman Perceptual Aberration and Physical Anhedonia Scales, and the Eysenck Psychoticism Scale. Group scores for these self-report ratings of 23 parent-pairs of patients with schizophrenia, 20 parent-pairs of patients with chronic nonpsychotic psychiatric disorder, and 19 parent-pairs of healthy comparison subjects are compared. RESULTS: Consistent with published evidence that self-report measures of psychosis-proneness and schizotypy do not consistently reflect familial risk factors that are specific for schizophrenia, scores on questionnaire measures of schizotypy did not distinguish the parents of patients with schizophrenia from the parents in the other two groups. CONCLUSIONS: Interview-based assessments of schizotypy better assess familial risk factors than self-report measures of schizotypy. Questionnaire measures of schizotypy should be supplemented by interview-based assessments when screening for individuals at risk of schizophrenia.

Adolescent↗
PubMed2000

Structural brain imaging and the prevention of schizophrenia: can we identify neuroanatomical markers for young people at risk for the development of schizophrenia?

OBJECTIVE: To examine the potential role of measures derived from structural brain imaging as phenotypic markers for the development of schizophrenia. METHOD: Literature review of results of MRI-based assessments of brain structure in patients with schizophrenia, their first-degree relatives and factors that affect interpretation of such results. RESULTS: Reliable differences in brain structure can be detected in patients with schizophrenia, including those experiencing a first episode of psychosis. Further research is required to determine whether these differences are progressive, how they relate to potential confounding factors such as comorbid substance abuse and the functional consequences of the relatively subtle changes observed. CONCLUSIONS: Further research is needed before structural brain change can be considered as a phenotypic marker for those at risk of developing schizophrenia. Large-scale collaborative research in clinical and normal volunteer groups using standardised assessment protocols would enable the early identification of those findings with predictive power in at-risk populations.

Adolescent↗
PubMed1999

Superior temporal gyral volumes and laterality correlates of auditory hallucinations in schizophrenia.

BACKGROUND: Previous studies have reported significant correlations, indicating an emerging relationship, between severity of auditory hallucinations and reduced size of temporal lobe cortical regions implicated in language processing. The present study used high-resolution magnetic resonance imaging (MRI) scanning, along with assessment of functional lateralization via a dichotic listening task (DLT), to extend these findings. METHODS: Thirty patients with schizophrenia and a history of auditory hallucinations participated in the study. All were completely right-handed. Eleven subjects were currently hallucinating at the time of the study. Volumetric T1-weighted MRI scans were obtained and regions of interest were manually traced using the BRAINS package (Andreasen et al 1993). Whole brain, bilateral temporal lobe, and anterior superior temporal gyrus volumes were calculated. Subjects completed a binaural consonant-vowel DLT. RESULTS: Increased severity of hallucinatory experience was significantly associated with smaller left anterior superior temporal gyrus volumes. Current hallucinators demonstrated a reduction in right ear advantage on the DLT. CONCLUSIONS: The results suggest that auditory hallucinations are subserved by a trait-like dysfunction in language-related neural networks, of which the superior temporal cortex forms one component. The findings are also consistent with theories proposing abnormal lateralization in the etiology of auditory hallucinations.

Adult↗
PubMed1999

Effects of prepulses and d-amphetamine on performance and event-related potential measures on an auditory discrimination task.

RATIONALE: Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimotor gating, that is the processing of the startle stimulus (S2) is inhibited by the interfering processing of a closely preceding prepulse (S1). It has been demonstrated that PPI is disrupted in a variety of mental disorders and that several neurotransmitter systems, including dopamine, participate in the modulation of sensorimotor gating. Previous studies have also shown that a task-relevant S1 enhances PPI in healthy subjects but not in schizophrenic patients. These findings indicate an influence of attentional processes on sensorimotor gating and an impairment of this modulation in schizophrenia. OBJECTIVE: Assuming a dopamine-mediated suppression of S1 processing as a mechanism of resource management and selective attention, which might be impaired in certain mental disorders, the present study investigated the effects of the indirect dopaminergic agonist d-amphetamine on prepulse-altered S2 discrimination and event related potentials (ERPs). METHODS: Twelve healthy volunteers were tested in a double-blind, placebo-controlled experimental design. Here, S2 is the target in a difficult Go/NoGo auditory discrimination task. RESULTS: Confirming our previous results, S2 processing is "accentuated" by a weak acoustic prepulse in healthy subjects, thus leading to a lower rate of errors of omission but also to more false alarms (i.e. a liberal response bias). This performance change correlated with a prepulse-induced increase in the amplitude of the P3 ERP towards non-targets ("prepulse-induced non-target positivity"; PINTP). In addition, the results of the present study show that under prepulse conditions amphetamine disrupts "S2 accentuation" associated with a dose-related reduction of the P2 component of the S1 response and a plasma level related reduction of PINTP. CONCLUSIONS: These data suggest an involuntary attentional shift towards S1 processing with increasing dopamine-release similar to that observed in patients with schizophrenia or OCD. It is concluded that sensory gating alters selective attention via dopaminergic modulation.

Acoustic Stimulation↗
PubMed1999

Changes in auditory selective attention and event-related potentials following oral administration of D-amphetamine in humans.

The effect of d-amphetamine on selective attention in humans was investigated by measuring event-related potentials (ERPs) during a complex auditory selective attention task (CSAT). The CSAT required subjects to make a button press response to infrequent target tones presented amongst tones that varied in pitch (high vs. low), location (left vs. right ear) and duration (51 ms vs. 102 ms). Healthy subjects completed the CSAT under three conditions: placebo, 10 mg and 20 mg d-amphetamine, at least one week apart. D-amphetamine produced a significant dose response increase in hit-rate and decrease in reaction time without changing false alarm rate. D-amphetamine reduced late PN to location irrelevant stimuli and pitch irrelevant stimuli in both the attended and unattended location. The effect of d-amphetamine was interpreted as a decrease in the maintenance of the attentional trace to irrelevant stimuli. However, these changes were accompanied by some evidence of processing of stimulus features in the unattended location. These results suggest that d-amphetamine improves selective attention, and decreases the maintenance of attention to irrelevant stimuli.

Administration, Oral↗
PubMed1999

Campylobacter upsaliensis gastroenteritis in childhood.

BACKGROUND: Campylobacter upsaliensis can cause gastroenteritis and bacteremia. Data on its epidemiology and role in pediatric gastroenteritis are limited. OBJECTIVE: To describe the incidence and clinical features of enteric C. upsaliensis infection in children and to compare these with similar data for Campylobacter jejuni. DESIGN AND METHODS: Medical records of all patients with enteric C. upsaliensis infection between 1992 and 1999 at the Royal Children's Hospital, Melbourne, were reviewed. A case-control study (age-matched 1:2) was performed to compare the severity of clinical disease and associated risk factors for infection with C. upsaliensis and C. jejuni. RESULTS: Of 18,516 specimens 666 (3.6%) were positive for C. jejuni and 19 (0.1%) were positive for C. upsaliensis. Records were available for 18 patients with C. upsaliensis gastroenteritis (mean age, 1.6 years; median age, 1.3 years; range, 3 months to 7 years; 14 male). Eleven patients (61%) presented with acute and 7 (39%) with chronic or intermittent diarrhea. The case-control study showed that fever (P = 0.03), acute diarrhea (P = 0.05) and rectal bleeding (P = 0.0006) were significantly less common in C. upsaliensis than in C. jejuni infection. CONCLUSION: C. upsaliensis is a rare cause of gastroenteritis in young children and, compared with C. jejuni infection, is associated with significantly lower rates of fever, acute diarrhea and rectal bleeding.

Campylobacter↗
PubMed1999

PCR amplification from fixed tissue indicates frequent involvement of Brachyspira aalborgi in human intestinal spirochetosis.

PCR procedures amplifying portions of the 16S rRNA and NADH oxidase genes of Brachyspira aalborgi and Serpulina pilosicoli were applied to DNA extracted from paraffin-embedded human colonic or rectal tissues from 30 Norwegian, Australian, and U.S. patients, 16 of whom had histologic evidence of intestinal spirochetosis (IS). B. aalborgi-specific sequences were identified by PCR in 10 of the IS patients (62.5%) but none of the others, while S. pilosicoli sequences were not detected in tissues from any patient. Direct sequencing of products from three of the positive samples provided further confirmation of the presence of B. aalborgi. B. aalborgi may be a more common cause of intestinal spirochetosis than has been previously thought.

Adolescent↗
PubMed1997

Dynamics of Clostridium difficile infection. Control using diet.

Understanding the dynamics of the establishment of C. difficile within the gut is vital to effective prevention, control and therapy of disease due to this nosocomial pathogen. Factors affecting the establishment of C. difficile in the gut were investigated including the role of bacterial metabolic products (BMPs), the composition of colonic flora, diet, and properties of the infecting strain. Concentrations of 9/12 bacterial metabolic products (BMPs), both volatile and non-volatile were significantly higher in mice which eliminated oral challenge with 10(8) spores of C. difficile (E mice) than in mice harbouring the organism (H mice). Growth of C. difficile in vitro was inhibited 10(4) fold at combinations of BMPs at concentrations found in stools of E mice but not in stools of H mice. The in situ production and concentrations of BMPs were increased by augmenting the amount of fermentable fibre in the diet. This resulted in elimination of C. difficile from 6/7 C. difficile colonized mice within 6 days of beginning a diet containing 20% fermentable fibre. Whereas mice fed diets containing 2% fermentable fibre or 20% non-fermentable fibre continued excreting the organism. Elimination of C. difficile was associated with increased concentrations of BMPs and changes in the numbers of organisms already present within the colonic flora. Properties of two microbial phenotypes (smooth (S), and rough (R)) of one strain of C. difficile were examined in vitro and the ID50s determined. The S phenotype survived, germinated and grew in media containing higher concentrations of BMPs, acquired iron when grown under iron restriction, utilized haem and bound Congo red more readily than the R phenotype. In mice fed the 2% fermentable fibre diet the ID50 for the S phenotype was 10(3) spores and 10(8) spores for the R phenotype, whereas for mice fed the 20% fermentable fibre diet it was > 10(6) spores for the S phenotype. The ability of this opportunistic pathogen to adapt to changing environmental conditions is an important factor in determining whether the organism will colonize and cause disease. Diets supplemented with fermentable fibre may be a valuable method of preventing and treating C. difficile related disease.

Animals↗
PubMed1997

The effect of decreased catecholamine transmission on ERP indices of selective attention.

This study examines the effect of decreased catecholamine transmission on event-related potential (ERP) indices of selective attention. Intravenous clonidine (1.5 micrograms/kg Catapres), droperidol (15 micrograms/kg Droleptan), or placebo were administered to healthy adult males prior to performance of a multidimensional auditory selective attention task (SAT) in which dichotically presented sequences of tone pips varied on dimensions of location (left or right ear), pitch (high or low), and duration (short or long). Subjects were required to make a button press response to infrequent "target" stimuli that matched a prespecified stimulus on the three dimensions. ERPs were recorded during the task. Clonidine led to a significant increase of processing negativity (PN) over 200-400 ms at the irrelevant location. Droperidol led to a significant increase in reaction time (RT), a significant decrease in hit rate, and an attenuation of PN over the 200- to 400-ms and 400- to 700-ms epochs. Neither substance led to a significant change in P3 amplitude. The role of catecholamines in the selective attention subprocesses of "tuning" and "switching" is discussed.

Adrenergic alpha-Agonists↗
PubMed1997

Molecular biological investigations into the role of the NMDA receptor in the pathophysiology of schizophrenia.

OBJECTIVE: There is increasing acceptance that schizophrenia is associated with a generalised disorder in cortical neurodevelopment. The aim of this paper is to review the evidence that this disorder may be accounted for by abnormalities in mechanisms mediated by the main family of excitatory neuroreceptors in cortical brain systems, the N-methyl-D-aspartate (NMDA) glutamatergic receptors. METHOD: The neurobiological evidence is presented for an abnormality in cortical development related to synaptic pathology in schizophrenia. The unique functions of the NMDA receptor in information processing are described, especially its role in learning and memory, and in neural plasticity and brain development. It is argued that the cellular and molecular mechanisms which underlie learning and memory also govern normal brain development. Studies examining abnormalities in glutamatergic transmission in schizophrenia are reviewed. RESULTS: There is a substantial literature in support of the possibility that NMDA receptor abnormalities may be involved in the neurodevelopmental predisposition to schizophrenia, as well as in symptom production. CONCLUSIONS: Research to determine the role of the NMDA receptor in the pathophysiology of schizophrenia is warranted and now feasible. To be successful, this research will require the application of molecular biology techniques to postmortem brain tissue studies, in addition to traditional histochemical approaches.

Cerebral Cortex↗