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Biomedical subjects

A J Thompson

Publications and source records attributed to A J Thompson.

At least 253 records · Page 14Linked to original sources
PubMed1996

Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis.

Although serial MRI studies of the brain in relapsing-remitting MS have demonstrated frequent asymptomatic disease activity, less is known about the spinal cord. We carried out monthly gadolinium-enhanced brain and spinal cord MRI scans over 1 year in 10 patients with relapsing-remitting MS. Six of the patients had a total of 11 clinical relapses, eight of which involved the spinal cord. A total of 167 active (enhancing or new nonenhancing) lesions in the brain and 19 in the spinal cord were present. Only one active brain lesion was symptomatic compares with six spinal cord lesions. Overall, one-third of new spinal cord lesions were symptomatic, and three-quarters of clinical spinal cord relapses were associated with a new MRI lesion in a location appropriate to the symptoms. Activity in both the spinal cord and brain was more common around the time of relapse. There was a strong association between the spinal cord and brain MRI activity. We did not detect progressive spinal cord atrophy from measurements of a spinal cord cross-sectional area. We conclude that, in relapsing-remitting MS, imaging of the brain alone will detect 90% of active lesions; spinal cord MRI using current technology will therefore provide only modest gains in treatment trials in which lesion activity is the primary outcome measure. The lack of ++progressive spinal cord atrophy in these patients, suggesting that significant axonal loss has not occurred, is in keeping with their good recovery after relapse. That brain and spinal cord lesions occur concurrently implies a systemic trigger for disease activity.

Adult↗
PubMed1996

Outcomes-based research in neurorehabilitation: the need for multidisciplinary team involvement.

There is a need for the evaluation of neurorehabilitation to reflect the integrated multidisciplinary input which is fundamental to the intervention process. The importance of multidisciplinary involvement in achieving this is discussed with particular reference to multiple sclerosis, which exemplifies the many problems inherent in chronic neurological disease that must be addressed in the evaluation of the rehabilitation programme. Some of the current difficulties of research in this specialty are raised, and suggestions made for the future.

Brain Diseases↗
PubMed1996

Findlay implantable two-stage centrifugal pump.

The Findlay centrifugal pump is unique in its two-stage pumping mechanisms and in its complementary interrelationship of the stages to each other and to the exit system, and it forms an extremely efficient unit. The first stage is a lift force pump as an inlet. The second and major stage is a shear force pump. Twenty-six prototypes, many multiply modified, have been hand fabricated, and most have had classic pump function analyses. Six pumps have demonstrated minimal hemolysis (3.5-5 h). At modest rotation speeds, it pumps water up to 10 L/min. Forty-four acute studies in normal dogs have been performed with the Findlay pump in a ventricular assist system. Blood flows through the pump ranged from 1.2 to 4.5 L/min. The conclusion is that the Findlay pump has the ability to operate with low blood damage, performs at acceptable rotational speed with reasonable hydraulic and mechanical efficiency, and is small and implantable.

Animals↗
PubMed1996

Clinical and magnetic resonance imaging predictors of disability in primary and secondary progressive multiple sclerosis.

The role of magnetic resonance imaging (MRI) in predicting disability in multiple sclerosis (MS) remains unclear. In this study 21 patients with primary and secondary progressive MS were reviewed 5 years following a serial MRI study of 6 months duration. In the secondary progressive group (n = 11) there was a significant relationship between the occurrence of enhancing lesions and clinical relapses during the initial 6 months and increase in disability 5 years later. For both groups change in disability over the initial study period was predictive of outcome. These results suggest that the presence and frequency of gadolinium enhancement (a marker of inflammation) and changes in disability over a short period are predictive of future deterioration in progressive patients.

Adult↗
PubMed1996

Detection of pathogen-related oral spirochetes, Treponema denticola, and Treponema socranskii in dental plaque from dogs.

Spirochetes have been observed in dental plaque from dogs, but specific spirochetes have not been identified. In particular, it is not known whether treponemes associated with periodontal diseases in humans also occur in dogs, and whether, like in humans, detection of specific treponemes correlates with periodontal status of dogs. Forty-two dogs were grouped according to the worst periodontal condition in the mouth, as determined by overt signs of inflammation and pocket probing depths. A representative specimen of dental plaque was obtained by pooling subgingival plaque collected from three uniform reference sites, irrespective of periodontal status at selected sites. The presence of pathogen-related oral spirochetes. Treponema denticola, and T. socranskii was determined using specific monoclonal antibodies in an immunocytochemical microscopic assay. All three treponemes were detected in all groups, but a significantly greater proportion of dogs with pocket probing depths > or = 5 mm had detectable treponemes, compared to dogs that were in periodontal health.

Animals↗
PubMed1995

Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss.

Proton magnetic resonance spectroscopy (MRS) and MRI were carried out in 11 patients with multiple sclerosis who had clinical evidence of severe cerebellar involvement, 11 multiple sclerosis patients (of similar age and disease duration) who had minimal or no signs of cerebellar disease, eight patients with autosomal dominant cerebellar ataxia (ADCA) and 11 healthy controls. In all subjects MRS was localized to cerebellar white matter (volumes of interest 3-6 ml). Apparent metabolite concentrations were calculated using the fully relaxed water spectrum as an internal standard of reference. The patients also underwent MRI to assess cerebellar volume and (in the two multiple sclerosis groups) lesion volume within the posterior fossa. Magnetic resonance spectroscopy from cerebellar white matter showed a highly significant reduction in the concentration of N-acetyl groups (NA) [which consists predominantly of N-acetylaspartate (NAA), a neuronal marker] in the multiple sclerosis group with cerebellar deficit compared with the multiple sclerosis group with minimal or no signs of cerebellar involvement, and healthy controls. Follow-up MRS performed in six of the multiple sclerosis patients 9 months later showed no change in the median NA concentration. The ADCA group showed a significant reduction of NA from a region of cerebellar white matter and also a reduction in the concentration of choline-containing compounds. The multiple sclerosis group with severe cerebellar deficit and the ADCA group both had significant cerebellar atrophy (suggesting nerve cell body and axon loss) compared with the multiple sclerosis patients with minimal or no signs of cerebellar deficit and healthy controls. The multiple sclerosis patients with cerebellar deficit had a significantly greater lesion volume in the posterior fossa, although the proportion of the spectroscopic voxel occupied by lesions was small, suggesting that axonal loss from normal appearing white matter also contributes to the observed reduction in NA. These results support the hypothesis that axonal loss is important in the development of persistent clinical disability in multiple sclerosis.

Adult↗
PubMed1995

Quantitative assessment of MRI lesion load in monitoring the evolution of multiple sclerosis.

In recent years, several segmentation techniques have been developed to quantify brain MRI lesion load in multiple sclerosis and are now being used increasingly for both evaluating the natural history of the disease and monitoring the efficacy of treatment. Such techniques have been applied extensively to conventional T2-weighted images; there is less experience to date with gadolinium-enhanced scans and newer MR parameters which are thought to reflect the more destructive aspects of the pathological process. Manual outlining of lesions on T2-weighted images is moderately accurate when performed by an experienced observer and has been validated in large clinical trials, but is very time consuming. Semi-automated intensity-based techniques appear to be more reproducible, but are still slow to perform. Faster techniques with higher reproducibility are still needed. The correlations between conventional T2 lesion load and clinical outcome is strong in patients seen at first presentation with clinically isolated syndromes suggestive of multiple sclerosis, but much weaker in established multiple sclerosis. The application of quantitative assessment of the MR parameters which are more specific for the disabling aspects of the pathological process (i.e. demyelination, axonal loss and spinal cord involvement) may improve the correlation with clinical status.

Brain↗
PubMed1995

Visual evoked potentials in phenylketonuria: association with brain MRI, dietary state, and IQ.

At separate institutions, pattern reversal visual evoked potentials (VEPs) were recorded in children and older patients with phenylketonuria and compared with MRI of the brain. In nine patients aged less than 14 years, who were still on a diet low in phenylalanine, VEPs were clearly abnormal in only one and the abnormalities seen on MRI were mild. In 27 patients aged 14-31 years VEPs were abnormal in more than 80%, with significant reduction of amplitude and prolongation of latency despite the general absence of visual symptoms and abnormalities on routine neuro-ophthalmological examination. Among the older patients there was no significant correlation between VEP measures and plasma phenylalanine or tyrosine concentrations; neither was the incidence of VEP abnormalities dependent on whether or not the patients were still on a low phenylalanine diet. Some VEP amplitude measures were inversely correlated with the MRI lesion score, perhaps reflecting the severity of white matter abnormalities in the parieto-occipital region. In the older patients the amplitude of VEPs to stimulation of the central 8 degrees of the visual field was significantly correlated with IQ. The study confirms the high incidence of subclinical visual pathway involvement in older children and adults with phenylketonuria, and suggests the possibility of a link between the abnormal appearance of subcortical white matter on MRI and a physiological index of function of the CNS. As there was no evidence of general intellectual decline, it is suggested that the correlation between central field VEP amplitude and IQ may reflect abnormal development during infancy. Abnormalities on MRI, on the other hand, seem to be more closely related to current dietary state and phenylalanine concentration.

Adolescent↗
PubMed1995

Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: a follow-up study.

We obtained two conventional unenhanced T2-weighted brain MRI scans, separated by an interval of 24 to 36 months, in 281 patients with multiple sclerosis (MS). At the time of each scan, clinical disability was rated using the Kurtzke Expanded Disability Status Scale (EDSS). Changes in disability between the two examinations correlated weakly but significantly with the number of new (Spearman's rank correlation coefficient = 0.13; p = 0.02) and enlarging (Spearman's rank correlation coefficient = 0.18; p = 0.002) MRI lesions. This result suggests that brain T2-weighted MRI is a useful supplementary marker of disease activity in definitive (phase III) clinical treatment trials in MS.

Adult↗
PubMed1995

The Functional Independence Measure: a comparative validity and reliability study.

The majority of measurement scales used to evaluate outcome in rehabilitation are ordinal in nature and consequently statistically valid assessments of change are difficult to make. The Functional Independence Measure (FIM) can be weighted to possess interval properties, potentially allowing more accurate analysis of change. In this study the FIM was compared to the Barthel Index (BI) to determine its validity, reliability and ease of use in two groups of 25 patients undergoing neurorehabilitation. The FIM was considered to be more valid than the BI, and equally reliable in the assessment of disability. When the two disability scores were compared using subjective and objective assessment the agreement between them was comparable, although neither was high.

Activities of Daily Living↗
PubMed1995

Interferon beta-1b in secondary progressive multiple sclerosis--outline of the clinical trial.

This manuscript describes the outline of a double-blind, placebo-controlled, (European), multicentre phase III study to evaluate the safety and efficacy of 8 MIU of interferon beta-Ib given subcutaneously every other day for 3 years in patients with secondary progressive multiple sclerosis. The primary efficacy variable of this trial is the time to confirmed neurological deterioration as documented by the Expanded Disability Status Scale. The essentials of the study design are presented, including the rationale for the performance of the study and the selection of both clinical and magnetic resonance imaging outcome parameters.

Adjuvants, Immunologic↗
PubMed1994

A chloroplast group I intron undergoes the first step of reverse splicing into host cytoplasmic 5.8 S rRNA. Implications for intron-mediated RNA recombination, intron transposition and 5.8 S rRNA structure.

The chloroplast 23 S rRNA gene of Chlamydomonas reinhardtii contains a self-splicing group I intron, Cr.LSU. Incubation of total RNA from C. reinhardtii with [alpha-32P]GTP produces a GTP-labeled RNA that is derived from Cr.LSU, but is approximately 95 nucleotides longer (and referred to as IA). We show that IA is derived from an intermolecular reaction of Cr.LSU with cytoplasmic 5.8 S rRNA; the 3'-terminal G of the intron becomes ligated to A64. This reaction, which was reproduced using synthetic RNAs, is identical to the first step of reverse splicing. The second step of reverse splicing did not occur with any efficiency, even though both P1 and P10-like helices can form between the reactive region of 5.8 S rRNA and the IGS of Cr.LSU. Cloning of IA provided a chimeric Cr.LSU precursor with the normal 3' exon substituted by 95 nucleotides of 5.8 S; this precursor spliced poorly despite having a potential P10 helix (between the 3'-exon and the IGS). The inefficient reverse splicing of Cr.LSU into 5.8 S RNA and poor forward splicing of the chimera may be explained by competition between helices P1 (between the 5'-exon and IGS) and P10; competition between P1 and P10 is apparently not a factor in forward splicing of the wild-type LSU precursor. The sequence of the 5.8 S gene of C. reinhardtii was determined, and the published RNA sequence revised. A secondary structure model of C. reinhardtii 5.8 S rRNA was proposed incorporating the requirement for base-pairing to the IGS of Cr.LSU. The resulting structure resembles that recently proposed for yeast 5.8 S rRNA, and has considerable advantages over previous models of C. reinhardtii 5.8 S rRNA. These data describe a novel example of a naturally occurring ribozyme reacting with a naturally occurring RNA of the same cell; implications for ribozyme-mediated RNA recombination and intron transposition via reverse splicing are discussed.

Animals↗
PubMed1994

Correlation of magnetization transfer ratio with clinical disability in multiple sclerosis.

We performed spin echo magnetic resonance imaging with and without application of an off-resonance saturation pulse in 43 patients with multiple sclerosis (MS), 10 age-matched controls, and 4 elderly asymptomatic patients with the radiological diagnosis of small-vessel disease. Magnetization transfer (MT) ratio images were obtained from these. All MS subgroups (primary progressive, secondary progressive, benign, early relapsing-remitting) showed significantly lower average lesion MT ratios than small-vessel disease patients. Secondary progressive MS patients showed significantly lower lesion MT ratios than those with benign disease, and there was an inverse correlation of disability with average lesion MT ratio. The degree of reduction of MT ratios is an indicator of the extent of tissue destruction. Thus, reduced MT ratios in MS may provide an indication of the degree of demyelination and axonal loss, both of which are likely to cause functional deficits in MS. We conclude that MT measurement is (1) a robust quantitative method that may increase the pathological specificity of magnetic resonance imaging, (2) has the potential to differentiate demyelination in MS from less destructive pathological changes, and (3) may be useful in monitoring modifications in tissue structure brought about by treatment.

Adult↗
PubMed1994

Benign and secondary progressive multiple sclerosis: a preliminary quantitative MRI study.

In a preliminary study, we compared by means of quantitative magnetic resonance imaging (MRI) methods (1) the T2 values and the decay characteristics of chronic brain lesions, (2) the T2 values of normal-appearing frontal white matter (NAWM) and (3) brain lesion volumes in patients with benign and secondary progressive multiple sclerosis (MS) in order to evaluate the mechanisms underlying the development of disability. Eleven clinically definite MS patients with either benign MS (n = 5) or secondary progressive MS (n = 6) were studied. Fifty-two chronic lesions (identified by comparison with MRI scans obtained at least 12 months previously) were identified. The mean T2 of large lesions (cross-sectional area greater than 41 mm2) and of the NAWM was similar in both clinical groups. However, small lesions had higher mean T2 values (P < 0.01) in the benign group, probably at least in part because of partial volume effects. Analysis of large lesions revealed biexponential T2 relaxation in 6 of 8 "secondary progressive" and in 2 of 16 "benign" lesions, perhaps indicating a greater degree of axonal loss in large lesions of patients with secondary progressive MS. Patients with secondary progressive MS had higher (although not significant) total and infratentorial lesion loads than those of the benign group. These preliminary findings suggest, but do not establish, that variations in the extent, site and pathological nature of lesions may all contribute to different patterns of disease evolution in MS.

Adolescent↗
PubMed1994

Magnetic resonance imaging in monitoring the treatment of multiple sclerosis patients: statistical power of parallel-groups and crossover designs.

Serial brain magnetic resonance (MR) imaging detects active lesions 5-10 times more frequently than the occurrence of clinical changes in patients with early relapsing-remitting and secondary progressive multiple sclerosis (MS). Based on monthly unenhanced and gadolinium enhanced MR findings in 23 unselected and untreated patients, the power of an MS treatment trial was calculated, using MR imaging activity as the primary measure of outcome. It was shown that a 80% reduction in the number of active lesions (i.e. an efficacy of 80%) should be detected using a placebo-controlled parallel-groups design with a power of 80%, if either 2 x 20 patients are scanned monthly for 4 months, or 2 x 30 patients monthly for 2 months. Short to medium term studies of new experimental treatments in MS, using MR imaging as the primary outcome measure, provide considerable statistical power in small patient populations studied over a short period of time.

Adult↗
PubMed1994

Increased expression of high affinity IL-2 receptors and beta-adrenoceptors on peripheral blood mononuclear cells is associated with clinical and MRI activity in multiple sclerosis.

Enhanced expression of beta-adrenoceptor densities on peripheral blood mononuclear cells (PBMCs) in progressive multiple sclerosis patients has been observed in a number of independent studies. A link between increased number of beta-adrenoceptors and inflammatory disease has been further indicated by studies in rheumatoid arthritis and relapsing-remitting multiple sclerosis patients. In a serial monthly assessment of relapsing-remitting multiple sclerosis patients, we have demonstrated that increased beta-adrenoceptors on PBMCs correlate with the expression of high affinity interleukin-2 receptors (IL-2Rs) and disease activity as determined by clinical and MRI findings. Magnetic resonance imaging activity was strongly correlated with IL-2R expression and it appears to be a sensitive marker of PBMC immunoactivation in multiple sclerosis. In vitro studies showed that beta-agonist stimulation of PBMCs reduces the IL-2R expression and suppresses cell proliferation following mitogenic stimulation. This observation may indicate a recovery role for the enhanced beta-adrenoceptor expression in multiple sclerosis. However, its therapeutic importance remains to be tested by appropriate trials using either beta-agonists or agents activating the second messenger system, c-AMP, in lymphocytes.

Adult↗