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Biomedical subjects

J M Fletcher

Publications and source records attributed to J M Fletcher.

At least 19 recordsLinked to original sources
PubMed2005

Promotor genotype of the platelet-derived growth factor receptor-alpha gene shows population stratification but not association with spina bifida meningomyelocele.

Neural tube defects (NTDs) constitute a major group of congenital malformations with an overall incidence of approximately 1-2 in 1,000 live births in the United States. Hispanic Americans have a 2.5 times higher risk than the Caucasian population. Spina bifida meningomyelocele (SBMM) is a major clinical presentation of NTDs resulting from lack of closure of the spinal cord caudal to the head. In a previous study of spina bifida (SB) patients of European Caucasian descent, it was suggested that specific haplotypes of the platelet-derived growth factor receptor-alpha (PDGFRA) gene P1 promoter strongly affected the rate of NTD genesis. In our study, we evaluated the association of PDGFRA P1 in a group of 407 parent-child triads (167 Caucasian, 240 Hispanics) and 164 unrelated controls (89 Caucasian, 75 Hispanic). To fully evaluate the association of PDGFRA P1, we performed both transmission-disequilibrium test (TDT) and association analyses to test the hypotheses that PDGFRA P1 was (1) transmitted preferentially in SBMM affected children and (2) associated with the condition of SBMM comparing affected children to unaffected controls. We did find that there was a different allelic and genotypic distribution of PDGFRA P1 when comparing Hispanics and Caucasians. However, neither ethnic group showed strong association between SBMM and the PDGFRA P1 region. These findings suggest that PDGFRA P1 does not have a major role in the development of SBMM.

Adult↗
PubMed2005

Enzyme replacement therapy for Gaucher disease in Australia.

AIM: To study the effectiveness of a specific national programme of enzyme replacement therapy (ERT) for patients with severe forms of Gaucher disease, a disorder of sphingolipid metabolism resulting from an inherited deficiency of the lysosomal enzyme beta-Glucocerebrosidase. METHODS: Prospective analysis of data submitted at entry and every 6 months on therapy. The responses of haemoglobin (Hb) and platelet (plt) concentrations, liver and spleen volumes were assessed. PATIENTS: Forty-eight patients were treated with ERT for a minimum of 6 months. Forty patients had Type 1 disease and eight had Type 3B. The age range was 1-70 years (median 24 years). Duration of therapy at the time of analysis was 6-114 months. RESULTS: Thirty-six per cent of patients started with a normal Hb increasing to 76% after 6 months. The mean improvement in Hb from baseline to the end of study period was 20 g/L, when the Hb was normal in 85% (41 patients). Thirty per cent of patients had a normal plt count at the start of therapy, with a more gradual increase in the count at 6 monthly intervals of 50, 91, 108 and 142% of starting value. Seventy-five per cent of patients had a normal plt count at the end of study. Spleen volumes reduced by a mean of 56% in 33 evaluable patients, and the liver by 27% in 30 of 38 evaluable patients. Eight patients had an increase in liver volume of 28%. CONCLUSION: Enzyme replacement therapy produced a spectrum of beneficial responses in patients with Gaucher disease, but all had some evidence of reversal of haematological complications and/or reduction in visceromegaly. Future analyses will examine the effect of therapy on bone disease, prepubertal growth and quality of life.

Adolescent↗
PubMed2004

Spatio-temporal brain activation profiles associated with line bisection judgments and double simultaneous visual stimulation.

We used magnetic source imaging (MSI) to investigate the spatio-temporal patterns of brain activity associated with line bisection judgments and double simultaneous visual stimulation in 14 healthy adults. Consistent with lesion and hemodynamic neuroimaging studies, we found the greatest number of activity sources in right inferior parietal cortex. These sources were most prominent, on average, between 200 and 300 ms after the onset of single (left, right, or center) target stimuli. A greater number of significant activity sources were found in right inferior parietal, occipital, and prefrontal cortices during bilateral compared with unilateral stimulus presentation. Based on these observations, we suggest that a more parsimonious physiological explanation of visual extinction than the hemispheric rivalry account may be the additional neuronal excitation required in right occipital and parietal cortices for accurate bilateral visual perception.

Adult↗
PubMed2002

Continuum of impulsiveness caused by auditory masking.

OBJECTIVE: Impulsivity is a hallmark of attention deficit/hyperactivity disorder (ADHD). Various auditory masking procedures can quantify the impulsivity caused by distracting background sounds. This study compares the impulsiveness and distraction caused by informational masking (unpredictable tones) with previously published data on central masking (contralateral noise) in children with and without ADHD. METHODS: Twenty-six normal and 14 children diagnosed as having ADHD (combined type), all between the ages of 7 and 13, indicated whether they heard a 512-ms, 500-Hz pure tone in a single-interval task under conditions of informational masking and in quiet. The masker consisted of 10 randomly selected frequencies between 1,000 and 2,500 Hz presented simultaneously at an overall level of 60 dB SPL. A maximum-likelihood method estimated thresholds and false alarm rates. RESULTS: There were no differences due to ADHD in thresholds or false alarm rates either with informational masking or in quiet. With informational masking, normal children had high false alarm rates, similar to those from children with ADHD under central masking. With informational masking, all children tended to say a stimulus was present when it was not. CONCLUSIONS: All children behave impulsively under some conditions. Pediatric patients with attention disorders can thus be reassured that impulsiveness with unpredictable background sounds is normal, to some extent. Response biases of children with ADHD may only diverge from normal in situations where distracting external stimuli have an intermediate level of predictability. A previous study showed that with central masking, children with ADHD are more impulsive than normal. There appears to be a limit to the uncertainty in auditory masking that can be tolerated by children. Children with ADHD become impulsive at lower levels of uncertainty than normal. Increasing the predictability of distracting background sounds may thus improve the performance of children with ADHD. Informational masking may, for normal listeners, mimic something of what it is like to have an attention deficit. ADHD can be profitably studied with auditory tasks.

Acoustic Stimulation↗
PubMed2002

Dyslexia-specific brain activation profile becomes normal following successful remedial training.

OBJECTIVES: To examine changes in the spatiotemporal brain activation profiles associated with successful completion of an intensive intervention program in individual dyslexic children. METHODS: The authors obtained magnetic source imaging scans during a pseudoword reading task from eight children (7 to 17 years old) before and after 80 hours of intensive remedial instruction. All children were initially diagnosed with dyslexia, marked by severe difficulties in word recognition and phonologic processing. Eight children who never experienced reading problems were also tested on two occasions separated by a 2-month interval. RESULTS: Before intervention, all children with dyslexia showed distinctly aberrant activation profiles featuring little or no activation of the posterior portion of the superior temporal gyrus (STGp), an area normally involved in phonologic processing, and increased activation of the corresponding right hemisphere area. After intervention that produced significant improvement in reading skills, activity in the left STGp increased by several orders of magnitude in every participant. No systematic changes were obtained in the activation profiles of the children without dyslexia as a function of time. CONCLUSIONS: These findings suggest that the deficit in functional brain organization underlying dyslexia can be reversed after sufficiently intense intervention lasting as little as 2 months, and are consistent with current proposals that reading difficulties in many children represent a variation of normal development that can be altered by intensive intervention.

Adolescent↗
PubMed2002

Urine amino and organic acids analysis in developmental delay or intellectual disability.

OBJECTIVES: To determine the proportion of urine amino and organic acids screening tests (UMS) undertaken for patients referred with developmental delay or intellectual disability (DD/ID), and within the group with DD/ID, to determine the diagnostic yield, the proportion of diagnoses with a therapy and the associated recurrence risks. METHODS: A retrospective review of request forms and results of UMS, in individuals older than 28 days, referred to the Women's and Children's Hospital, North Adelaide, between 1 January 1992 and 31 December 1998 was carried out. Urine was analysed by ion exchange chromatography (amino acids), gas chromatography/mass spectrometry (organic acids), colorimetric assay (orotic acid) and stable isotope-dilution mass spectrometry (trimethylamine). RESULTS: A total of 3316 samples were received, 1447 being from patients with DD/ID. A diagnosis was determined for 1.8% of all referrals. For patients with DD/ID, the diagnostic yield was 1.1%, with a similar yield for isolated DD/ID and DD/ID with other features (9/828 vs 7/619; chi2 = 0.006; P = 0.93). Specific therapies were available for 69% of diagnoses associated with DD/ID and 87.5% had known Mendelian or mitochondrial inheritance. CONCLUSION: Urine metabolic screening is an important part of the evaluation of children with DD/ID as it can enable families to make reproductive decisions and children to receive appropriate therapy early.

Amino Acids↗
PubMed2001

Perception of voice and tone onset time continua in children with dyslexia with and without attention deficit/hyperactivity disorder.

Tasks assessing perception of a phonemic contrast based on voice onset time (VOT) and a nonspeech analog of a VOT contrast using tone onset time (TOT) were administered to children (ages 7.5 to 15.9 years) identified as having reading disability (RD; n = 21), attention deficit/hyperactivity disorder (ADHD; n = 22), comorbid RD and ADHD (n = 26), or no impairment (NI; n = 26). Children with RD, whether they had been identified as having ADHD or not, exhibited reduced perceptual skills on both tasks as indicated by shallower slopes on category labeling functions and reduced accuracy even at the endpoints of the series where cues are most salient. Correlations between performance on the VOT task and measures of single word decoding and phonemic awareness were significant only in the groups without ADHD. These findings suggest that (a) children with RD have difficulty in processing speech and nonspeech stimuli containing similar auditory temporal cues, (b) phoneme perception is related to phonemic awareness and decoding skills, and (c) the potential presence of ADHD needs to be taken into account in studies of perception in children with RD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Analysis of the effect of changing environmental conditions on the expression patterns of exported surface-associated proteins of the oral pathogen Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans has been specifically implicated in the aetiology of one or more of the periodontal diseases, conditions in which inflammation of the gums is associated with destruction of the alveolar bone supporting the teeth. In these diseases there is loss of attachment of the gums (gingivae) to the teeth forming a periodontal pocket. The microenvironment of this pocket is extremely complex and it is likely that there will be substantial variation in the environmental conditions operating in this habitat. The aim of the current investigation was to study the effect of disease-relevant environmental factors on the production and release of secreted surface- associated proteins of A. actinomycetemcomitans. These secreted proteins contain many of the virulence determinants of this organism. A range of environmental conditions were investigated: growth in a CO(2)-enriched aerobic atmosphere vs anaerobic growth, presence of serum or blood, biofilm vs planktonic mode of growth and iron depletion. Differential expression of a number of the secreted surface-associated proteins was observed under different growth conditions and these included the glycolytic enzyme triose phosphate isomerase. An ability to adapt to prevailing environmental conditions may facilitate the survival of the organism in the changing microIenvironment of the periodontal pocket.

Adaptation, Biological↗
PubMed2001

The functional neural architecture of components of attention in language-processing tasks.

Using functional magnetic resonance imaging we examined three important dimensions of attentional control (selective attention, divided attention, and executive function) in 25 neurologically normal, right-handed men and women, using tasks involving the perception and processing of printed words, spoken words, or both. In the context of language-processing manipulations: selective attention resulted in increased activation at left hemisphere parietal sites as well as at inferior frontal sites, divided attention resulted in additional increases in activation at these same left hemisphere sites and was also uniquely associated with increased activation of homologous sites in the right hemisphere, and executive function (measured during a complex task requiring sequential decision-making) resulted in increased activation at frontal sites relative to all other conditions. Our findings provide support for the belief that specific functional aspects of attentional control in language processing involve widely distributed but distinctive cortical systems, with mechanisms associated with the control of perceptual selectivity involving primarily parietal and inferior frontal sites and executive function engaging specific sites in frontal cortex.

Adult↗
PubMed2001

Attention processes in children with shunted hydrocephalus versus attention deficit-hyperactivity disorder.

Children with congenital hydrocephalus, children with attention deficit-hyperactivity disorder, and normal controls were evaluated with measures of focused attention (Visual Orienting and Detection Task), sustained attention (continuous performance test), and attention shifting (Wisconsin Card Sorting Test). Components from these tasks have been linked to attention systems mediated by anterior or posterior brain networks. Children with congenital hydrocephalus showed an inability to focus and shift attention, which specifically implicated impairment of the disengage and move components of the posterior brain attention system. Children with attention deficit-hyperactivity disorder displayed the expected performance patterns on measures of focused attention once their difficulties with sustained attention were taken into account. However, they showed problems with shifting and sustaining attention, which are commonly associated with the anterior brain attention system.

Achievement↗
PubMed2001

Fasting medium chain acyl-coenzyme A dehydrogenase--deficient children can make ketones.

Medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency classically presents as hypoketotic hypoglycemia. Under-production of ketones has been presumed to be the cause of hypoketosis, but this has never been proven. Stable isotope dilution studies of ketone kinetics were performed on three well children with homozygous 985G MCAD deficiency using 1,3-13C2 sodium acetoacetate and 1,2,3,4-13C4 sodium 3-hydroxybutyrate to ascertain the rates of ketone production, interconversion, and use. All children were fasted for 9 to 11.5 hours before the beginning of the study period. Euglycemia was maintained in all cases. Ketone kinetics were calculated using a two-accessible pool model and showed normal ketone production in all three children compared with published control data from children fasted for a similar length of time. There is no evidence for underproduction or overuse of ketones in these MCAD-deficient children, at least when they are well. We propose that another factor, such as fever, may be required to reduce ketone production and result in the biochemical phenotype recognized in unwell children.

3-Hydroxybutyric Acid↗
PubMed2001

Lifetime and novel psychiatric disorders after pediatric traumatic brain injury.

OBJECTIVE: To assess lifetime and current psychiatric disorders at least 1 year after traumatic brain injury (TBI) in children and adolescents. METHOD: Forty-six youths who sustained a TBI between the ages of 6 through 15 years were evaluated at least 1 year post-TBI to identify the presence of lifetime and/or novel psychiatric disorders. Semistructured interviews of the parent and child and standardized parent self-report rating instruments were used. RESULTS: Attention-deficit/hyperactivity disorder and depressive disorders were the most common lifetime and novel diagnoses. A wide variety and high rate of novel psychiatric disorders were identified; 74% of these disorders persisted in 48% of the injured children. Internalizing disorders were more likely to resolve than externalizing disorders. Both interviews and parent ratings were sensitive to current externalizing behaviors; interviews more often detected internalizing disorders, whereas parent ratings also identified cognitive difficulties. CONCLUSIONS: Findings were generally consistent with previous research demonstrating the high rate of novel psychiatric disorders following pediatric TBI. Psychiatric interviews were sensitive in identifying both lifetime and novel disorders.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Age-related changes in regional brain activation during phonological decoding and printed word recognition.

Using magnetic source imaging, age-related changes in spatiotemporal brain activation profiles associated with printed word recognition and phonological decoding (pseudoword reading) were examined in 27 adults and 22 children without reading problems. Adults showed a distinct spatiotemporal profile during reading of both types of print consisting of bilateral activation of occipital cortices, followed by strongly left-predominant activation of basal temporal regions, and, finally, left hemisphere temporoparietal (including the angular gyrus) and inferior frontal activation. Children lacked the clear temporal distinction in the engagement of basal and temporoparietal areas and displayed significantly weaker activation of the left inferior frontal gyrus. In addition, the consistent hemispheric asymmetries in the degree of activation of basal temporal regions that were present in the adult readers were not apparent in the children. In contrast, the strong left hemisphere preponderance in the degree of activation of temporoparietal areas was present in children as well as adults, regardless of the type of print they were asked to read. The data suggest that the degree of specialization of cortical regions for reading, as well as the pattern of regional interactions that supports this specialization, may change with age.

Adolescent↗
PubMed2001

Mapping of receptive language cortex in bilingual volunteers by using magnetic source imaging.

OBJECT: There are conflicting claims in the functional imaging literature concerning whether different languages are represented by distinct brain mechanisms in individuals who are proficient in more than one language. This interesting theoretical issue has practical implications when functional imaging methods are used for presurgical language mapping. To address this issue the authors compared the location and extent of receptive language cortex specific to English and Spanish in neurologically intact bilingual volunteers by using magnetic source imaging. METHODS: Areas of the cortex that were specialized for receptive language functions were identified separately for each language in 11 healthy adults who were bilingual in English and Spanish. The authors performed exactly the same procedures used routinely for presurgical receptive language mapping. In each bilingual individual, the receptive language-specific map always encompassed the posterior portion of the superior temporal gyrus. In every case, however, substantial differences in the receptive language maps were also observed for the two languages, regardless of whether each participant's first language was English or Spanish. CONCLUSIONS: Although the reasons for such differences and their ultimate significance in identifying the cerebral mechanisms of language are subject to continuing investigation, their presence is noteworthy and has practical implications for the surgical management of patients with lesions in the temporal and parietal regions of the dominant hemisphere.

Adult↗
PubMed2001

Plant antioxidants: colour me healthy.

Plants make a variety of compounds in response to environmental stress, many of which function as antioxidants when consumed. The plants' own defences against oxidative stress can be used for your benefit, prolonging your life by acquiring their protection. By eating plenty of vegetables and fruit, you may help to significantly reduce the risk of many age-related degenerative diseases.

Aging↗
PubMed2000

Brain activation profiles in dyslexic children during non-word reading: a magnetic source imaging study.

The purpose of the study was to identify spatiotemporal brain activation profiles associated with phonological decoding in dyslexic children using magnetic source imaging. For this purpose maps of regional cerebral activation were obtained from eleven children diagnosed with dyslexia and ten children without reading problems during engagement in a pseudoword rhyme-matching task. All dyslexic children showed aberrant activation maps consisting of reduced activity in temporoparietal areas in the left hemisphere (including the posterior part of the superior temporal, angular and supramarginal gyri) and increased activity in the right homotopic region. In contrast, the two groups of children did not differ in the degree of activity in basal temporal areas that typically precedes temporoparietal activation. This is the first study to demonstrate the existence of distinct activation profiles associated with phonological decoding in individual dyslexic children.

Adolescent↗
PubMed2000

Brain mechanisms for reading: the role of the superior temporal gyrus in word and pseudoword naming.

The purpose of this study was to test the neurological validity of a dual-route model of reading by asking patients, who were undergoing electrocortical stimulation mapping, to read words with irregular print-to-sound correspondences and pseudowords. Brain activation profiles were also obtained from these patients during an auditory and a visual word recognition task using whole-head magnetic source imaging. We demonstrated that reading is subserved by at least two brain mechanisms that are anatomically dissociable. One mechanism subserves assembled phonology and depends on the activity of the posterior part of the left superior temporal gyrus (STGp), whereas the second is responsible for addressed phonology and does not necessarily involve this region. The contribution of STGp to reading appears to be based on its specialization for phonological analysis operations, involved in the processing of both spoken and written language.

Adult↗