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N Roberts

Publications and source records attributed to N Roberts.

At least 19 recordsLinked to original sources

Localisation of connective tissue and inhibition of autofluorescence in the human optic nerve and nerve head using a modified picrosirius red technique and confocal microscopy.

The use of picrosirius red to localise connective tissue in thin tissue sections viewed by bright-field microscopy is well documented. Its use on thin tissue sections imaged by fluorescence confocal microscopy has also been reported. Here we describe modifications to published procedures that allow picrosirius red staining of thick 60-microm sections and their subsequent analysis by confocal microscopy. The use of phosphomolybdic acid pre-treatment was found to be essential for confocal analysis; in addition to preventing non-specific staining, it also quenched tissue autofluorescence. By incubating sections free-floating, pre-treating them with phosphomolybdic acid for 30 min and imaging them using an argon ion laser we were able to use confocal microscopy to image the entire depth of 60-microm human optic nerve and nerve head sections stained with picrosirius red. The application of this modified picrosirius red and confocal microscopy technique should be useful for analysing the three-dimensional structure of the optic nerve and other tissues with a similarly complex arrangement of connective tissue.

Adult

Infratentorial atrophy on magnetic resonance imaging and disability in multiple sclerosis.

Loss of tissue volume in the central nervous system may provide an index of fixed neurological dysfunction in multiple sclerosis. Recent magnetic resonance studies have shown a modest relationship between clinical disability rating scores and transverse sectional area of the cervical spinal cord. To explore further the relationship between atrophy and disability in multiple sclerosis, we estimated the volumes of infratentorial structures from MRIs in a cross-sectional study of 41 patients, 21 with relapsing-remitting multiple sclerosis and 20 with secondary progressive multiple sclerosis. We used the Cavalieri method of modern design stereology with point counting to estimate the volume of brainstem, cerebellum and upper cervical spinal cord from three-dimensional MRIs acquired with an MPRAGE (Magnetization-prepared Rapid Acquisition Gradient Echo) sequence. The volume of the upper (C1-C3) cervical spinal cord was significantly correlated with a composite spinal cord score derived from the appropriate Functional Scale scores of the Expanded Disability Status Scale (r = -0.50, P < 0.01). The cerebellar (r = 0.49, P < 0.01) and brainstem (r = 0.34, P < 0.05) volumes correlated with the Scripp's Neurological Disability Rating Scale scores. The upper cervical cord volumes (r = -0.39, P < 0.01), but not the brainstem or cerebellar volumes, were significantly associated with disease duration. MRI-estimated structural volumes may provide a simple index of axonal and/or myelin loss, the presumed pathological substrates of irreversible impairment and disability in multiple sclerosis.

Activities of Daily Living

Three dimensional MRI estimates of brain and spinal cord atrophy in multiple sclerosis.

OBJECTIVE: The association between brain atrophy and permanent functional deficits in multiple sclerosis and the temporal relation between atrophy and the clinical disease course have seldom been investigated. This study aims to determine the amount of infratentorial and supratentorial atrophy in patients by comparison with healthy controls, to establish the relation between atrophy and disability, and to derive the rates of volume loss in individual patients from their estimated disease durations. METHODS: Three dimensional acquired MRI was performed on 20 relapsing-remitting and 20 secondary progressive multiple sclerosis patients and 10 control subjects. Volume data on infratentorial and supratentorial structures were obtained using the Cavalieri method of modern design stereology in combination with point counting. Corpus callosal sectional area and "T2 lesion load" were also determined. RESULTS: Significantly reduced infratentorial and cerebral white matter volumes and corpus callosal sectional areas occurred in all patients compared with controls (p=0.0001-0.004). Mean estimates of volume loss in the cohort were -21%, -19%, -46%, and -12% for the brain stem, cerebellum, upper cervical cord and white matter, respectively, and -21% for the corpus callosal sectional area. Analysis of the amount of atrophy (volume differences between patients and controls) showed that upper cervical cord and cerebral white matter atrophy correlated with the expanded disability status scale (r=-0.37 and -0.37, p=0.018-0.023) and the Scripps neurologic rating scale scores (r=+0.49 and +0.43, p=0.002-0.007). There was no relation between estimated volume loss in the supratentorial and infratentorial compartments. The "T2 lesion load" was associated with ventricular enlargement and corpus callosal atrophy (r=+0.50 and -0.55, p=0.0003-0.0012). Infratentorial atrophy rates correlated with baseline exacerbation rates (r=-0.50 to -0.48, p=0.0016-0.0021) and were higher in relapsing-remitting than secondary progressive patients (p=0.009-0.02). CONCLUSIONS: Significant cerebral and spinal cord volume reductions occurred in both patient subgroups compared with controls. Functional correlates were found with estimated volume loss in the upper cervical cord and cerebral white matter. Particularly for infratentorial structures, estimated rates of atrophy were higher in relapsing-remitting than secondary progressive patients, suggesting that atrophy, perhaps mainly due to tract degeneration, begins early in multiple sclerosis and may relate predominantly to acute inflammatory events, with or without other gradual non-inflammatory processes later in the disease course.

Adult

Quantitative analysis of diurnal variation in volume and water content of lumbar intervertebral discs.

The Cavalieri method of modern design stereology has been used in combination with magnetic resonance imaging (MRI) to obtain unbiased estimates of the volume of the lumbar intervertebral discs immediately at the end of a day of normal activity and again following a night's rest. In addition, pixel-by-pixel mapping of the T2-relaxation time has been used to characterize objectively the tissues of the intervertebral discs. The mean increase in height of seven female subjects of average age 21 years (range 19-23 years) measured with a stediometer was 19.3 mm (range 8-26 mm). Image analysis showed that the mean overnight increase in volume of lumbar discs was 1300 mm3 (range 100-2700 mm3). The increase in volume of the disc was accompanied by an increase in the T2-relaxation time of the nucleus pulposus. This suggests that the change in disc volume is most probably caused by a preferential increase in the water content of the nucleus pulposus.

Adult

Restriction endonuclease-mediated selective polymerase chain reaction: a novel assay for the detection of K-ras mutations in clinical samples.

The enriched polymerase chain reaction (PCR) assay has been used extensively in the detection of ras gene mutations in many types of human malignancies. Although it is very sensitive, it has a number of features that limit its use in the routine diagnostic laboratory. The aim of this study was to develop a novel enriched PCR strategy, in which the concurrent activity of the restriction enzyme BstNI and Taq polymerase allowed the amplification of mutant K-ras while inhibiting the formation of wild-type product. This restriction endonuclease-mediated selective PCR assay uses three sets of primers, together with BstNI, in the reaction mix, and the amplification products are analyzed by gel electrophoresis. The reliability of the restriction endonuclease-mediated selective PCR assay to detect activated K-ras was determined in a variety of clinical samples, including 139 fresh colorectal carcinomas and 113 paraffin-embedded blocks from 80 separate tumors of the colon and rectum, pancreas, breast, or kidney. Codon 12 mutations of the K-ras oncogene were identified in DNA from both fresh and paraffin-embedded tumors in a rapid, sensitive, and reproducible manner. Mutations were detected in 33 (24%) of the fresh colorectal cancers and 16 (20%) of the paraffin-embedded tumors. These results were 97% concordant in cases in which paraffin blocks and fresh specimens from the same tumor were available for analysis. We conclude that restriction endonuclease-mediated selective PCR is a sensitive, rapid, and robust assay for the detection of point mutations in a variety of clinical samples. Importantly, there is no need for manipulation of the sample once the PCR has been set up, and therefore, the chance of contamination is significantly reduced. In contrast to previous assays, restriction endonuclease-mediated selective PCR is not labor intensive, and its format is suitable for use in routine diagnostic laboratory.

Adenocarcinoma

Face processing impairments after encephalitis: amygdala damage and recognition of fear.

Face processing and facial emotion recognition were investigated in five post-encephalitic people of average or above-average intelligence. Four of these people (JC, YW, RB and SE) had extensive damage in the region of the amygdala. A fifth post-encephalitic person with predominantly hippocampal damage and relative sparing of the amygdala (RS) participated, allowing us to contrast the effects of temporal lobe damage including and excluding the amygdala region. The findings showed impaired recognition of fear following bilateral temporal lobe damage when this included the amygdala. For JC, this was part of a constellation of deficits on face processing tasks, with impaired recognition of several emotions. SE, YW and RB, however, showed relatively circumscribed deficits. Although they all had some problems in recognizing or naming famous faces, and had poor memory for faces on the Warrington Recognition Memory Test, none showed a significant impairment on the Benton Test of Facial Recognition, indicating relatively good perception of the face's physical structure. In a test of recognition of basic emotions (happiness, surprise, fear, sadness, disgust and anger), SE, YW and RB achieved normal levels of performance in comparison to our control group for all emotions except fear. Their results contrast with those of RS, with relative sparing of the amygdala region and unimpaired recognition of emotion, pointing clearly toward the importance of the amygdala in the recognition of fear.

Aged

Fetal and fetal brain volume estimation in the third trimester of human pregnancy using gradient echo MR imaging.

The Cavalieri method has been applied in combination with gradient echo magnetic resonance imaging (MRI) to investigate the increase in the volume of the fetus and fetal brain in the third trimester of pregnancy. Eighteen women with singleton pregnancies were recruited. Birthweights for the fetuses all lay within the 10-90th centile based on Liverpool data. A regression analysis, weighted using values derived from the coefficient of error predicted for each volume estimate, revealed a linear relationship between total fetal volume and gestational age (R2 = 0.88) and between fetal brain volume and gestational age (R2 = 0.71) during the third trimester. Fetal volume increased by an average of 25.2 ml per day and fetal brain volume increased by an average of 2.3 mL per day. Fetal brain volume is on average a constant proportion (10%, SD = 2%) of total fetal volume throughout the third trimester. Volume data were also obtained for eight fetuses diagnosed as abnormal. The volume of seven of the eight abnormal fetuses fell outside the 95% confidence interval established from the data obtained for the normal fetuses. However, for only three of the eight abnormal fetuses did brain volume fall outside the 95% confidence interval established for normals, possibly due to brain sparing occurring in asymmetrical growth retardation. The volume of the fetus and fetal brain may be readily estimated directly using the Cavalieri method and magnetic resonance imaging. These parameters represent potentially useful information for assessing fetal growth.

Adult

Recurrent acute upper airway obstruction after anterior cervical fusion.

A 67-year-old man presented with cervical myelopathy for which a C3/4 discectomy and anterior fusion was performed. Recurrent episodes of acute upper airway obstruction necessitated laryngoscopy and endotracheal intubation. Drainage of a prevertebral collection of CSF and surgical repair of a dural tear corrected the obstructive symptoms. Management of the difficult airway is discussed.

Aged

Case-control study of stroke and the quality of hypertension control in north west England.

OBJECTIVE: To examine the risk of stroke in relation to quality of hypertension control in routine general practice across an entire health district. DESIGN: Population based matched case-control study. SETTING: East Lancashire Health District with a participating population of 388,821 aged < or = 80. SUBJECTS: Cases were patients under 80 with their first stroke identified from a population based stroke register between 1 July 1994 and 30 June 1995. For each case two controls matched with the case for age and sex were selected from the same practice register. Hypertension was defined as systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg, or both, on at least two occasions within any three month period or any history of treatment with antihypertensive drugs. MAIN OUTCOME MEASURES: Prevalence of hypertension and quality of control of hypertension assessed by using the mean blood pressure recorded before stroke) and odds ratios of stroke (derived from conditional logistic regression). RESULTS: Records of 267 cases and 534 controls were examined; 61% and 42% of these subjects respectively were hypertensive. Compared with non-hypertensive subjects hypertensive patients receiving treatment whose average pre-event systolic blood pressure was controlled to < 140 mm Hg had an adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or poorly controlled (> or = 160 mm Hg) or untreated had progressively raised odds ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure were similar; both were independent of initial pressures before treatment. Around 21% of strokes were thus attributable to inadequate control with treatment, or 46 first events yearly per 100,000 population aged 40-79. CONCLUSIONS: Risk of stroke was clearly related to quality of control of blood pressure with treatment. In routine practice consistent control of blood pressure to below 150/90 mm Hg seems to be required for optimal stroke prevention.

Adult

The relationship between the magnetic resonance imaging appearance of the lumbar spine and low back pain, age and occupation in males.

The purpose of this study was to undertake a critical review of the potential role of magnetic resonance imaging (MRI) in the evaluation of low back pain (LBP) and to determine if there were differences in the MRI appearances between various occupational groups. The study group, 149 working men (78 aged 20-30 years and 71 aged 31-58 years) from five different occupations (car production workers, ambulance men, office staff, hospital porters and brewery draymen), underwent MRI of the lumbar spine. Thirty-four percent of the subjects had never experienced LBP. Twelve months later, the examination was repeated on 89 men. Age-related differences were seen in the MRI appearances of the lumbar spine. Disc degeneration was most common at L5/S1 and was significantly more prevalent (P < 0.01) in the older age group (52%) than in the younger age group (27%). Although LBP was more prevalent in the older subjects there was no relationship between LBP and disc degeneration. No differences in the MRI appearance of the lumbar spine were observed between the five occupational groups. Overall, 45% had 'abnormal' lumbar spines (evidence of disc degeneration, disc bulging or protrusion, facet hypertrophy, or nerve root compression). There was not a clear relationship between the MRI appearance of the lumbar spine and LBP. Thirty-two percent of asymptomatic subjects had 'abnormal' lumbar spines and 47% of all the subjects who had experienced LBP had 'normal' lumbar spines. During the 12-month follow-up period, 13 subjects experienced LBP for the first time. However, there was no change in the MRI appearances of their lumbar spines that could account for the onset of LBP. Although MRI is an excellent technique for evaluating the lumbar spine, this study shows that it does not provide a suitable pre-employment screening technique capable of identifying those at risk of LBP.

Absenteeism

Automatic analysis of cerebral atrophy.

3D MR data obtained for 10 healthy control subjects have been used to build a brain atlas. The atlas is built in four stages. First, a set of features that are unambiguously definable and anatomically relevant need to be computed for each item in the database. The chosen features are crest lines along which the maximal principal curvature of the surface of the brain is maximal in its associated principal direction. Second, a nonrigid registration algorithm is used to determine the common crest lines among the subjects in the database. These crest lines form the structure of the atlas. Third, a set of crest lines is taken as a reference set and a modal analysis is performed to determine the fundamental deformations that are necessary to bring the individual data in line with the reference set. The deformations are averaged and the set of mean crest lines becomes the atlas. Finally, the standard deviation of the deformations between the atlas and the items in the database defines the normal variation in the relative positions of the crest lines in a healthy population. In a fully automatic procedure, the crest lines on the surface of the brain adjacent to the cerebral ventricles in a patient with primary progressive aphasia were compared to the atlas; confirmation that the brain of this patient demonstrates atrophy was provided by stereological analysis that showed that the volume of the left cerebral hemisphere is 48.8 ml (CE 2.8%) less than the volume of the right cerebral hemisphere in the region of the temporal and frontal lobes. When the amplitude of the deformations necessary to register the crest lines obtained for the patient with the atlas were greater than three standard deviations beyond the variability inherent in the atlas, the deformation was considered significant. Four of the main deformation modes of the longest crest line of the surface of the brain adjacent to the cerebral ventricles were significantly different in the patient with primary progressive aphasia compared to the atlas. The ventricles are preferentially enlarged in the left cerebral hemisphere. Furthermore, they are closer together posteriorly and further apart anteriorly than in the atlas. These observations may be indicative of the atrophy of the temporal and frontal lobes of the left cerebral hemisphere noted in the patient. Ultimately, the approach may provide a useful screening technique for identifying brain diseases involving cerebral atrophy. Serial studies of individual patients may provide insights into the processes controlling or affected by particular disease.

Aged

Hominid thumb strength predicted by high resolution magnetic resonance imaging and force measurements in living subjects.

This study investigates whether in-vivo measurements of the morphology of the pollical distal phalanx (PDP) can be used to predict the maximum force that can be exerted by the thumb in flexion at the interphalangeal joint. A predictive equation was obtained via which measurements of fossil PDP's can be used to predict flexion force in hominids. A home-built insertable coil assembly, which increased the available magnetic field gradient strength from 10 to 40 (mT) m-1, was used to acquire high resolution T1-weighted 3D SPGR Magnetic Resonance (MR) images of the left and right thumbs of nine volunteers. The subjects' age, sex, weight, height and self-assessed hand-dominance were recorded. The MR images were transferred to a computer for reformatting of sections in the transverse and volar plane (VP). Measurements were made of the maximum length (ML), breadth (MB), tuft breadth (MT) and joint depth (JD) of the PDP. For each subject the maximum flexion force that could be exerted by each thumb was measured. The mean maximum flexion force generated was 8.21 kg (range 5.68-13.13 kg). Considerable inter-individual variability was observed in the magnitude of the force difference between the left and right thumbs and this is greatest in individuals with the strongest thumbs. The best model produced by multiple linear regression analysis of all the available data has a value of r = 0.77 and needs only the two covariates of sex and weight, i.e. FORCE = 2.217 + 0.6651 x WEIGHT + 2.488 x SEX. However, in order to be useful for predicting the maximum flexion force of the thumb in hominids the model should only contain those parameters which can be measured for fossil PDP's. Accordingly, the best predictive model has a value of r = 0.73 and needs only the two covariates of ML and JD, i.e. FORCE = -10.28 + 0.2053 x ML + 1.571 x JD. The maximum force predicted for any of the hominid fossil PDP's was not significantly different from those recorded for the volunteers in the present study, although they were on average somewhat lower than those obtained for modern humans. This may be a reflection of the hominid's overall smaller body weights.

Animals