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Biomedical subjects

A J Richardson

Publications and source records attributed to A J Richardson.

At least 19 recordsLinked to original sources
PubMed2002

Auditory frequency discrimination in adult developmental dyslexics.

Developmental dyslexics reportedly discriminate auditory frequency poorly. A recent study found no such deficit. Unlike its predecessors, however, it employed multiple exposures per trial to the standard stimulus. To investigate whether this affects frequency discrimination in dyslexics, a traditional two-interval same-different paradigm (2I_1A_X) and a variant with six A-stimuli per trial (2I_6A_X) were used here. Frequency varied around 500 Hz; interstimulus interval (ISI) ranged between 0 and 1,000 msec. Under 2I_1A_X, dyslexics always had larger just noticeable differences (JNDs) than did controls. Dyslexic and control JNDs were equal at shorter ISIs under 2I_6A_X, but dyslexics became worse than controls at longer ISIs. Signal detection analysis suggests that both sensory variance and trace variance are larger in dyslexics than in controls.

Adult↗
PubMed2001

SPECT neuroimaging in schizophrenia with religious delusions.

Functional neuroimaging techniques such as single-positron emission computed tomography (SPECT) and positron emission tomography (PET) offer considerable scope for investigating disturbances of brain activity in psychiatric disorders. However, the heterogeneous nature of disorders such as schizophrenia limits the value of studies that group patients under this global label. Some have addressed this problem by considering schizophrenia at a syndromal level, but so far, few have focussed at the level of individual symptoms. We describe the first neuroimaging study of the specific symptom of religious delusions in schizophrenia. 99mTc HMPAO high-resolution SPECT neuroimaging showed an association of religious delusions with left temporal overactivation and reduced occipital uptake, particularly on the left.

Adult↗
PubMed2001

Associations between central and peripheral measures of phospholipid breakdown revealed by cerebral 31-phosphorus magnetic resonance spectroscopy and fatty acid composition of erythrocyte membranes.

1. Abnormal neuronal membrane phospholipid metabolism is increasingly recognized as being of central importance to a number of neuropsychiatric disorders. Currently, two important indices of membrane phospholipid metabolism tend to be measured: the ratio of the areas of the phosphomonoester (PME) and phosphodiester (PDE) peaks from in vivo cerebral phosphorus magnetic resonance spectroscopy (31P MRS) studies; and erythrocyte membrane fatty acid concentrations. Thus far, there have been no studies comparing these two indices to ascertain the extent to which they agree. 2. The authors measured these indices in nine normal adults. Spectral localization was achieved using four-dimensional chemical shift imaging methods and erythrocyte membrane fatty acid concentrations (from blood samples taken at the time of scanning) were measured using gas liquid chromatography. 3. Levels of PDE (an index of phospholipid catabolism), measured using cerebral 31P MRS, were significantly correlated with reduced concentrations of the highly unsaturated fatty acids docosahexaenoic acid (DHA) (r = -0.68, p < 0.05) and eicosapentaenoic acid (EPA) (r -0.78, p < 0.02). No significant correlations were found between peripheral concentrations of any highly unsaturated fatty acids and PME levels, nor between their essential fatty acid precursors and either PDE or PME levels. Other 31-phosphorus metabolites also showed no significant correlations with the blood fatty acid measures. 4. The correlations between central measures of PDE and peripheral measures of DHA and EPA provide validation of cerebral 31P MRS as a non-invasive technique for the study of membrane phospholipid metabolism in vivo.

Adult↗
PubMed2001

Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK.

We describe a family-based sample of individuals with reading disability collected as part of a quantitative trait loci (QTL) mapping study. Eighty-nine nuclear families (135 independent sib-pairs) were identified through a single proband using a traditional discrepancy score of predicted/actual reading ability and a known family history. Eight correlated psychometric measures were administered to each sibling, including single word reading, spelling, similarities, matrices, spoonerisms, nonword and irregular word reading, and a pseudohomophone test. Summary statistics for each measure showed a reduced mean for the probands compared to the co-sibs, which in turn was lower than that of the population. This partial co-sib regression back to the mean indicates that the measures are influenced by familial factors and therefore, may be suitable for a mapping study. The variance of each of the measures remained largely unaffected, which is reassuring for the application of a QTL approach. Multivariate genetic analysis carried out to explore the relationship between the measures identified a common factor between the reading measures that accounted for 54% of the variance. Finally the familiality estimates (range 0.32-0.73) obtained for the reading measures including the common factor (0.68) supported their heritability. These findings demonstrate the viability of this sample for QTL mapping, and will assist in the interpretation of any subsequent linkage findings in an ongoing genome scan.

Child↗
PubMed2001

Could platelet activating factor play a role in developmental dyslexia?

Post-mortem studies by Galaburda and colleagues on the brains of developmental dyslexics found characteristic neuronal abnormalities: ectopias, microgyria, and fewer large-soma cells in sensory thalamus. An association between dyslexia and immune dysfunction has also been proposed. We describe a mechanism which may explain these observations. Platelet-activating factor (PAF) is a pro-inflammatory lipid implicated in neurological disorders. We propose that PAF may also be involved in dyslexia.

Brain↗
PubMed2001

Perinatal inferior vena cava thrombosis and absence of the infrarenal inferior vena cava.

We report a case of infrarenal absence of the inferior vena cava (IVC) presenting as a major iliofemoral deep venous thrombosis in an adolescent. This is the first report of infrarenal IVC absence in which IVC thrombosis has been demonstrated in the perinatal period. We propose an association between perinatal IVC thrombosis and subsequent infrarenal IVC absence. In addition, the case demonstrates the importance of assessment for anatomical anomalies in patients presenting with apparently idiopathic deep venous thrombosis.

Child↗
PubMed2001

Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover.

The n-3 essential fatty acid eicosapentaenoic acid (EPA) was added to the conventional antidepressant treatment of a treatment-resistant severely depressed and suicidal male patient with a seven-year history of unremitting depressive symptoms. The niacin skin flush test and cerebral magnetic resonance scanning were carried out at baseline and nine months later. The addition of ethyl-EPA led to a dramatic and sustained clinical improvement in all the symptoms of depression, including a cessation of previously unremitting severe suicidal ideation, within one month. Symptoms of social phobia also improved dramatically. During the nine-month period the volumetric niacin response increased by 30%, the relative concentration of cerebral phosphomonesters increased by 53%, and the ratio of cerebral phosphomonesters to phosphodiesters increased by 79%, indicating reduced neuronal phospholipid turnover. Registered difference images showed that the EPA treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.

Adult↗
PubMed2000

Chromosomal integration of the green fluorescent protein gene in lactic acid bacteria and the survival of marked strains in human gut simulations.

An integration vector was constructed to allow introduction of the gfp gene into the chromosomes of Gram-positive bacteria. Integration depends on homologous recombination between a short 458-nt sequence of the tet(M) gene in the vector and a copy of Tn916 in the host chromosome. Strains of Lactococcus lactis IL1403, Enterococcus faecalis JH2-SS, and Streptococcus gordonii DL1 stably marked with single chromosomal copies of the gfp were readily visualised by epifluorescence microscopy. The marked L. lactis strain survived poorly in a continuous culture system inoculated with human faecal flora, while the laboratory E. faecalis strain was lost at approximately the dilution rate of the fermenter.

Bacteria↗
PubMed2000

Red cell and plasma fatty acid changes accompanying symptom remission in a patient with schizophrenia treated with eicosapentaenoic acid.

The administration of the omega-3 fatty acid eicosapentaenoic acid (EPA) to a drug-naïve patient with schizophrenia, untreated with conventional antipsychotic medication, led to a dramatic and sustained clinical improvement in both positive and negative symptoms. This was accompanied by a correction in erythrocyte membranes of abnormalities in both n-3 and n-6 highly unsaturated fatty acids (HUFAs). Therefore EPA is able to reverse the phospholipid abnormalities previously described in schizophrenia. This reversal is associated with, and is likely to be the cause of, the clinical improvement. In particular, EPA appears to have reversed the depletion of not only n-3 HUFAs, but also of membrane arachidonic acid, possibly via inhibition of HUFA-specific phospholipase A(2), an enzyme which removes HUFAs from the S(N)2 position of membrane phospholipids, or by activation of a fatty acid coenzyme A ligase. Correction by EPA of abnormalities in both enzyme systems is not ruled out.

Adult↗
PubMed2000

Monocular occlusion can improve binocular control and reading in dyslexics.

Developmental dyslexia is a neurodevelopmental condition which causes 5-10% of children to have unexpected difficulty learning to read. Many dyslexics have impaired development of the magnocellular component of the visual system, which is important for timing visual events and controlling eye movements. Poor control of eye movement may lead to unstable binocular fixation, and hence unsteady vision; this could explain why many dyslexics report that letters appear to move around, causing visual confusion. Previous research has suggested that such binocular confusion can be permanently alleviated by temporarily occluding one eye. The aim of the present study was therefore to assess the binocular control and reading progress of dyslexic children with initially unstable binocular control after the left eye was patched. One hundred and forty-three dyslexics were studied. They were selected from children aged 7-11 years referred to a learning disabilities clinic if they were dyslexic and had unstable binocular control. They were randomly assigned to wear yellow spectacles with or without the left lens occluded, and were followed for 9 months. Significantly more of the children who were given occlusion gained stable binocular fixation in the first 3 months (59%) compared with children given the unoccluded glasses (36%). This advantage was independent of IQ or initial reading ability. Furthermore, at all the 3-month follow-ups, children were more likely to have gained stable binocular control if they had been wearing the occluded glasses. Gaining stable binocular control significantly improved reading. The children who did so with the help of occlusion improved their reading by 9.4 months in the first 3 months, compared with 3.9 months in those who were not patched and did not gain stable fixation. Over the whole 9 months, children who received occlusion and gained stable fixation nearly doubled their rate of progress in reading compared with those who remained unstable. At all the follow-ups the reading of those given occlusion was significantly better than that of those not occluded. Thus monocular occlusion helped children with unstable binocular control to gain good binocular fixation. If they gained stability, they made significantly faster reading progress. The progress made by the children who gained stable fixation was much greater than that achieved with other remedial techniques.

Child↗
PubMed1999

Cerebral ventricular asymmetry in schizophrenia: a high resolution 3D magnetic resonance imaging study.

Lateral ventricular volume asymmetries in schizophrenia were studied using high resolution 3D magnetic resonance imaging in conjunction with segmentation and quantitation techniques. Comparisons were made between two clinical syndromes that have been associated with opposite patterns of functional hemispheric activation, namely an active and a withdrawn syndrome. Ratios of both left to right ventricular volume and left to right ventricle-to-brain ratios differed significantly between the two groups. These results primarily reflected differences in the left ventricular volume, in keeping with previous reports which have usually implicated left hemispheric structural abnormalities in schizophrenia. It is suggested that a syndromal approach might help to resolve some of the inconsistencies in the existing literature on lateralised neuroanatomical differences in schizophrenia.

Adult↗
PubMed1999

Laterality changes accompanying symptom remission in schizophrenia following treatment with eicosapentaenoic acid.

INTRODUCTION: A patient with severe intractable symptoms of schizophrenia was treated for 6 months with a fatty acid supplement, primarily as a test of the hypothesis that membrane phospholipid metabolism is abnormal in schizophrenia. His symptomatology was predominantly positive, consistent with an 'Active' syndrome thought to reflect a relative imbalance of left over right hemispheric activation. Longitudinal studies have previously shown changes in functional lateralisation with symptom remission in schizophrenia, hence this was examined at intervals over the 6-month period. METHOD: The subject was a 30-year-old male with DSM-IV schizophrenia. For 2 years prior to this study his clinical profile had not changed and he had remained free of neuroleptic medication. Treatment with 30 ml/day of emulsion rich in eicosapentaenoic acid was started, and clinical ratings were made at monthly intervals for 6 months. Motor laterality had been assessed using Annett's handedness scale and pegboard task 1 year pre-baseline, and this was repeated at 0, 3 and 6 months from the start of treatment. RESULTS: As measured by the Schedules for the Assessment of Positive Symptoms and Negative Symptoms, a marked reduction in his symptoms was first apparent at 2-month follow-up; further improvement followed, so that at the 6-month point few symptoms remained. Corresponding to his clinical improvement, the patient's performance on the pegboard task at 3-month follow-up had shifted from a strong right-hand advantage to near symmetry, owing to a marked improvement in his left-hand scores. On retest at 6 months this change in asymmetry was also maintained. CONCLUSIONS: These findings suggest that treatment with certain fatty acids may have significant benefits in the management of schizophrenia. They are also consistent with existing evidence that an Active syndrome of schizophrenia reflects a left over right hemispheric imbalance which is functional in nature, and can therefore change with symptom remission.

Adult↗
PubMed1999

A prospective randomized multicentre comparison of expanded polytetrafluoroethylene and gelatin-sealed knitted Dacron grafts for femoropopliteal bypass.

PURPOSE: To compare graft patency between expanded polytetrafluoroethylene (PTFE) and gelatin-sealed knitted Dacron for femoropopliteal bypass. METHODS: A prospective, multicentre trial was performed in 108 patients randomized to receive either a PTFE or Dacron prosthetic graft. Distal anastomosis was above knee in 75 and below knee in 33 patients. RESULTS: Primary patency at 1, 2 and 3 years was 72, 52 and 52% for PTFE, and 70, 56 and 47% for Dacron (P = 0.87). Secondary patency at 1, 2 and 3 years was 74, 54 and 54% for PTFE and 78, 70 and 53% for Dacron (P = 0.39). The most significant predictors of early graft failure were poor vessel run-off (P = 0.04) and critical limb ischaemia (P = 0.04). CONCLUSION: There was no difference in graft patency between PTFE and Dacron for femoropopliteal bypass.

Aged↗
PubMed1999

A quantitative-trait locus on chromosome 6p influences different aspects of developmental dyslexia.

Recent application of nonparametric-linkage analysis to reading disability has implicated a putative quantitative-trait locus (QTL) on the short arm of chromosome 6. In the present study, we use QTL methods to evaluate linkage to the 6p25-21.3 region in a sample of 181 sib pairs from 82 nuclear families that were selected on the basis of a dyslexic proband. We have assessed linkage directly for several quantitative measures that should correlate with different components of the phenotype, rather than using a single composite measure or employing categorical definitions of subtypes. Our measures include the traditional IQ/reading discrepancy score, as well as tests of word recognition, irregular-word reading, and nonword reading. Pointwise analysis by means of sib-pair trait differences suggests the presence, in 6p21.3, of a QTL influencing multiple components of dyslexia, in particular the reading of irregular words (P=.0016) and nonwords (P=.0024). A complementary statistical approach involving estimation of variance components supports these findings (irregular words, P=.007; nonwords, P=.0004). Multipoint analyses place the QTL within the D6S422-D6S291 interval, with a peak around markers D6S276 and D6S105 consistently identified by approaches based on trait differences (irregular words, P=.00035; nonwords, P=.0035) and variance components (irregular words, P=.007; nonwords, P=.0038). Our findings indicate that the QTL affects both phonological and orthographic skills and is not specific to phoneme awareness, as has been previously suggested. Further studies will be necessary to obtain a more precise localization of this QTL, which may lead to the isolation of one of the genes involved in developmental dyslexia.

Adolescent↗
PubMed1999

Molecular analysis of the microbial diversity present in the colonic wall, colonic lumen, and cecal lumen of a pig.

Random clones of 16S ribosomal DNA gene sequences were isolated after PCR amplification with eubacterial primers from total genomic DNA recovered from samples of the colonic lumen, colonic wall, and cecal lumen from a pig. Sequences were also obtained for cultures isolated anaerobically from the same colonic-wall sample. Phylogenetic analysis showed that many sequences were related to those of Lactobacillus or Streptococcus spp. or fell into clusters IX, XIVa, and XI of gram-positive bacteria. In addition, 59% of randomly cloned sequences showed less than 95% similarity to database entries or sequences from cultivated organisms. Cultivation bias is also suggested by the fact that the majority of isolates (54%) recovered from the colon wall by culturing were related to Lactobacillus and Streptococcus, whereas this group accounted for only one-third of the sequence variation for the same sample from random cloning. The remaining cultured isolates were mainly Selenomonas related. A higher proportion of Lactobacillus reuteri-related sequences than of Lactobacillus acidophilus- and Lactobacillus amylovorus-related sequences were present in the colonic-wall sample. Since the majority of bacterial ribosomal sequences recovered from the colon wall are less than 95% related to known organisms, the roles of many of the predominant wall-associated bacteria remain to be defined.

Anaerobiosis↗
PubMed1998

Sensitivity to dynamic auditory and visual stimuli predicts nonword reading ability in both dyslexic and normal readers.

BACKGROUND: Developmental dyslexia is a specific disorder of reading and spelling that affects 3-9% of school-age children and adults. Contrary to the view that it results solely from deficits in processes specific to linguistic analysis, current research has shown that deficits in more basic auditory or visual skills may contribute to the reading difficulties of dyslexic individuals. These might also have a crucial role in the development of normal reading skills. Evidence for visual deficits in dyslexia is usually found only with dynamic and not static stimuli, implicating the magnocellular pathway or dorsal visual stream as the cellular locus responsible. Studies of such a dissociation between the processing of dynamic and static auditory stimuli have not been reported previously. RESULTS: We show that dyslexic individuals are less sensitive both to particular rates of auditory frequency modulation (2 Hz and 40 Hz but not 240 Hz) and to dynamic visual-motion stimuli. There were high correlations, for both dyslexic and normal readers, between their sensitivity to the dynamic auditory and visual stimuli. Nonword reading, a measure of phonological awareness believed crucial to reading development, was also found to be related to these sensory measures. CONCLUSIONS: These results further implicate neuronal mechanisms that are specialised for detecting stimulus timing and change as being dysfunctional in many dyslexic individuals. The dissociation observed in the performance of dyslexic individuals on different auditory tasks suggests a sub-modality division similar to that already described in the visual system. These dynamic tests may provide a non-linguistic means of identifying children at risk of reading failure.

Acoustic Stimulation↗
PubMed1998

Metabolic abnormalities in developmental dyslexia detected by 1H magnetic resonance spectroscopy.

BACKGROUND: Neurological and physiological deficits have been reported in the brain in developmental dyslexia. The temporoparietal cortex has been directly implicated in dyslexic dysfunction, and substantial indirect evidence suggests that the cerebellum is also implicated. We wanted to find out whether the neurological and physiological deficits manifested as biochemical changes in the brain. METHODS: We obtained localised proton magnetic resonance spectra bilaterally from the temporo-parietal cortex and cerebellum of 14 well-defined dyslexic men and 15 control men of similar age. FINDINGS: We found biochemical differences between dyslexic men and controls in the left temporo-parietal lobe (ratio of choline-containing compounds [Cho] to N-acetylaspartate [NA] p< or =0.01) and right cerebellum (Cho/NA, p< or = 0.01; creatine [Cre] to NA p< or =0.05; (not significant). We found lateral biochemical differences in dyslexic men in both these brain regions (Cho/NA in temporo-parietal lobe, left vs right, p< or =0.01; Cre/NA in cerebellum, left vs right, p< or =0.001). We found no such lateral differences in controls. There was no significant relation between the degree of contralateral chemical difference and handedness in dyslexic or control men. INTERPRETATION: We suggest that the observed differences reflect changes in cell density in the temporo-parietal lobe in developmental dyslexia and that the altered cerebral structural symmetry in dyslexia is associated with abnormal development of cells or intracellular connections or both. The cerebellum is biochemically asymmetric in dyslexic men, indicating altered development of this organ. These differences provide direct evidence of the involvement of the cerebellum in dyslexic dysfunction.

Adult↗