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C M Ellis

Publications and source records attributed to C M Ellis.

At least 19 recordsLinked to original sources
PubMed2005

HER2 amplification status in breast cancer: a comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis scoring techniques.

AIMS: To compare the results of breast cancer sections with HercepTesttrade mark immunohistochemistry (IHC) scores ranging from 0 to 3+ with fluorescence in situ hybridisation (FISH) for HER2 amplification. The HER2 digital scoring application of the Micrometastasis Detection System (MDS) was used, together with manual scoring of FISH and HercepTest, to determine whether this system provides an accurate alternative. METHODS: Paraffin wax embedded sections were stained using HercepTest and analysed by eye and automated quantitative image analysis. FISH was performed using the PathVysion fluorescent probe and scored by eye and automated quantitative image analysis using MDS. RESULTS: Of 114 cases, 26% were amplified by FISH, whereas only 18% scored 3+; 32% of IHC 2+ cases were amplified by FISH, and one showed borderline amplification. Six percent of IHC negative cases (0 or 1+) were amplified by FISH, and one showed borderline amplification. Of IHC 3+ cases, 10% were non-amplified by FISH. Classification discrepancies were seen in 18% of HercepTest cases scored by eye and using the MDS system. MDS was consistent with visual FISH scoring and correctly differentiated most ambiguous visual IHC scores. CONCLUSIONS: FISH provides a more accurate and consistent scoring system for determining HER2 amplification than HercepTest. The MDS system provides a reliable, consistent alternative to visual IHC and FISH scoring. IHC is still a valuable technique to aid in identification of isolated or heterogeneous tumour populations for subsequent FISH analysis, and a combined FISH and HercepTest approach to all breast cancer cases may be the most efficient strategy.

Biomarkers, Tumor↗
PubMed2001

Volumetric analysis reveals corticospinal tract degeneration and extramotor involvement in ALS.

BACKGROUND: Pathologic changes in the motor cortex and corticospinal tracts in ALS may be reflected by abnormal signal intensities on conventional MRI. The sensitivity of these changes in detecting underlying pathology remains unclear. METHOD: The authors used automated image analysis to quantify volumes of cerebral gray and white matter in 16 patients with ALS (eight limb onset, eight bulbar onset) and eight normal controls. Previously they had demonstrated a reduction in N-acetyl aspartate/creatine + phosphocreatine (NAA/[Cr + PCr]) measured by (1)H-MRS in the subcortical white matter in the motor cortex region in the patients with bulbar-onset ALS. To determine whether this resulted from axonal degeneration, they also compared gray and white matter volumes in the patients with limb- and bulbar-onset ALS. RESULTS: There were no differences in the total brain volumes of gray or white matter for the three subject groups (p > 0.23). Comparison of the total ALS group and controls revealed localized deficits in gray matter volume centered on Brodmann areas 8, 9, and 10 bilaterally. Comparison of the patients with limb- and bulbar-onset ALS revealed deficits in the white matter volume in the bulbar-onset group, extending bilaterally from the precentral gyrus into the internal capsule and brainstem, consistent with the course of the corticospinal tract. There was no loss in gray matter volume in the precentral gyri. CONCLUSIONS: The loss of gray matter in the frontal regions (total ALS group) provides further support that ALS is a multisystem disorder. In addition, there is in vivo evidence of axonal degeneration in the subcortical white matter in the motor region in patients with bulbar-onset ALS. This is consistent with a "dying back" process affecting cortical motoneurons in bulbar-onset ALS.

Adult↗
PubMed2001

Linkage and allelic association of chromosome 5 cytokine cluster genetic markers with atopy and asthma associated traits.

Linkage and association of polymorphic markers in the chromosome 5q31-q33 cytokine cluster to atopy and asthma associated phenotypes have been reported by a number of groups. To investigate this region, 29 polymorphic markers were used to genotype a combined set of 233 families. These markers were ordered based upon the genetic data, supplemented by published genetic and physical maps. Significant two-point linkage was observed for asthma (most significant marker IRF1, P = 0.0002) and atopy (CD14SNP, P = 0.0001). Allelic association was observed between D5S463 and atopy (P = 0.002) and the skin prick test index (P = 0.04). The data support the possibility of three asthma/atopy loci in the 5q31-q33 region, each with a relatively small effect.

Alleles↗
PubMed2000

Quantitative proton magnetic resonance spectroscopy of the subcortical white matter in motor neuron disease.

BACKGROUND: Using proton magnetic resonance spectroscopy, the authors have previously demonstrated a reduction in the N-acetyl aspartate/(creatine and phosphocreatine) (NAA/(Cr + PCr)) ratio in the motor region in bulbar-onset MND patients, attributed to neuronal loss or dysfunction leading to a reduction in NAA. We have expanded this analysis to evaluate absolute concentrations of NAA, (Cr + PCr) and choline-containing compounds (Cho) in the subcortical white matter in the motor region in 16 MND patients (8 with bulbar onset and 8 with limb onset) and 8 healthy, age-matched controls. METHODS: Single voxel 1H-MRS was performed using a PRESS localization sequence. Metabolite concentrations were determined using the water signal as an internal standard. RESULTS: We found no differences in the concentrations of NAA ([NAA]), (Cr + PCr) ([Cr + PCr]) or Cho ([Cho]) in the motor region on comparing the total MND group and controls (P > 0.3). No difference was found in [NAA] in the bulbar-onset group compared with the limb-onset group (P = 0.70), but [Cr + PCr] was significantly higher in the bulbar-onset group (P = 0.04). CONCLUSIONS: Our results suggest that [Cr + PCr] may be affected by the pathological process in MND, and this should be considered in the interpretation of metabolite peak area ratios. The elevated (Cr + PCr) may represent gliosis in the subcortical white matter in the motor cortex region.

Adult↗
PubMed2000

Phenotypic differences between African and white patients with motor neuron disease: a case-control study.

There is increasing evidence that race may affect the phenotype in some neurodegenerative diseases. To investigate this in motor neuron disease a retrospective case-control study has been carried out on 15 negroid African and 45 white patients with the disease seen over 8 years. Each African was compared with three age and sex matched white patients with motor neuron disease. There were no statistically significant differences in age of onset or the mean duration of disease in the two groups. The chance of presenting with the "flail arm" variant of motor neuron disease was four times as high in the African group than the white group (odds ratio 4.33, p=0. 05, 95% confidence interval 0.99-18.92). Although no overall differences in survival were seen between the two groups, in those with the flail arm variant, four out of the six African patients had died whereas all six white arm patients were alive at the censoring date of 1 January 1999 (median follow up 38.5 months). It is concluded that race may influence the phenotype and progression of motor neuron disease.

Africa↗
PubMed1999

Diffusion tensor MRI assesses corticospinal tract damage in ALS.

BACKGROUND: A number of neurophysiologic and neuroimaging techniques have been evaluated in the research setting to assess upper motor neuron (UMN) damage in ALS. Changes in tissue structure in the CNS modify the diffusional behavior of water molecules, which can be detected by diffusion tensor MRI. OBJECTIVES: To explore the hypothesis that degeneration of the motor fibers in ALS would be reflected by changes in the diffusion characteristics of the white matter fibers in the posterior limb of the internal capsule and that these changes could be detected by diffusion tensor MRI. METHODS: We studied 22 patients with El Escorial definite, probable, or possible ALS-11 with limb onset (mean age 54.5 +/- 10.7 years) and 11 with bulbar onset (mean age 49.6 +/- 11.7 years)-and compared them with 20 healthy, age-matched controls (mean age 46.0 +/- 12.6 years). We assessed central motor conduction time (CMCT), threshold to stimulation, and silent period using transcranial magnetic stimulation. Diffusion tensor MRI was performed using a 1.5-T GE Signa system (Milwaukee, WI) fitted with Advanced NMR hardware and software capable of producing echo planar MR images. Data were acquired from seven coronal slices centered to include the posterior limb of the internal capsule. Maps of the mean diffusivity, fractional anisotropy, and T2-weighted signal intensity were generated. RESULTS: There were no differences between the subject groups on measures of CMCT, threshold to stimulation, and silent period. However, the CMCT correlated with clinical measures of UMN involvement. We found a significant increase in the mean diffusivity and reduction in fractional anisotropy along the corticospinal tracts between the three subject groups, most marked in the bulbar-onset group. The fractional anisotropy correlated with measures of disease severity and UMN involvement, whereas the mean diffusivity correlated with disease duration. CONCLUSION: The results support the use of diffusion tensor MRI in detecting pathology of the corticospinal tracts in ALS.

Adult↗
PubMed1999

Limb contractures in levodopa-responsive parkinsonism: a clinical and investigational study of seven new cases.

We describe six patients with classical levodopa-responsive Parkinson's disease (PD) and one case of levodopa-responsive familial juvenile dystonia-parkinsonism with fixed contractures of the hands, feet or legs. In most patients contractures became established over a short period (2 months-2 years) but a considerable time after onset of parkinsonism (mean 13 years). Mean disease duration was 17 years, and all patients had severe levodopa-induced dyskinesias, either biphasic or peak dose, in the affected limb prior to onset of the contracture. Nerve conduction studies excluded peripheral ulnar nerve lesions in all patients with one exception, who was found to have a mild bilateral ulnar entrapment neuropathy. Transcranial magnetic stimulation performed in five of the seven patients showed shorter mean central motor conduction time in the affected than in the unaffected limb. Results of magnetic resonance imaging of the brain performed in a subgroup of patients were normal, with no evidence to suggest multiple system atrophy, cerebral infarction or focal abnormalities of the basal ganglia. We conclude that hand and feet contractures are not necessarily restricted to parkinson plus syndromes and may complicate otherwise typical PD in the absence of a structural or peripheral nervous cause. Striatal dopaminergic deficiency, particularly long-standing, may have a role in the pathogenesis of limb contractures in PD.

Adult↗
PubMed1999

Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil.

Functional magnetic resonance imaging (fMRI) can be used to detect regional brain responses to changes in sensory stimuli. We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome, using a multiplexed visual and auditory stimulation paradigm. In both normal and narcoleptic subjects, mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex. Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours, with a reverse pattern in narcoleptic subjects (P = 0.007). The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant. The alerting action, and imaging response, to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal (8 given modafinil, 4 placebo) and 12 narcoleptic subjects (8 modafinil, 4 placebo). Modafinil caused an increase in self-reported levels of alertness in 7 of 8 narcoleptic subjects, but there was no significant difference between mean pretreatment and post-treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil. However, in the modafinil-treated group of 8 normal and 8 narcoleptic subjects, there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation (visual, P = 0.002; and auditory, P = 0.001). No correlation was observed in placebo-treated subjects (P = 0.99 and 0.77, respectively). Although limited by the small number of subjects, and the lack of an objective measure of alertness, the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil. Functional magnetic resonance imaging may be a valuable addition to established studies of attention.

Acoustic Stimulation↗
PubMed1999

Distinct hyperintense MRI signal changes in the corticospinal tracts of a patient with motor neuron disease.

Neuroimaging in motor neuron disease (MND) is currently performed to exclude other pathologies, though abnormalities may be seen which are consistent with the diagnosis. We report a patient with rapidly progressive MND exhibiting extensive changes on a variety of contemporary magnetic resonance images, which is most likely to represent severe corticospinal tract degeneration.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Nocturnal subcutaneous apomorphine infusion in Parkinson's disease and restless legs syndrome.

OBJECTIVES: Nocturnal disabilities leading to fragmented sleep arising from parkinsonian off period related complications are common, under-reported and are difficult to treat. In this study, we evaluate the use of nocturnal continuous subcutaneous overnight apomorphine infusion in Parkinson's disease and restless legs syndrome. METHODS: Six parkinsonian patients and 2 patients with restless legs syndrome with nocturnal disabilities refractory to conventional oral therapy were assessed using a sleep diary while on standard treatment and during nocturnal apomorphine infusion. Three patients agreed to assessments during placebo infusion with normal saline. RESULTS: Apomorphine led to a dramatic reduction of nocturnal awakenings, nocturnal off periods, pain, dystonia and nocturia in parkinsonian patients. In patients with restless legs syndrome, apomorphine reduced nocturnal discomfort, reduced leg movements and improved pain and spasm scores significantly. Placebo infusion reproduced pain, nocturnal spasms and sleep disruption. CONCLUSION: This study suggests that overnight apomorphine infusion may be effective in overcoming refractory nocturnal disabilities in selected patients with Parkinson's disease and restless legs syndrome.

Adult↗
PubMed1999

Use of human intravenous immunoglobulin in lower motor neuron syndromes.

OBJECTIVE: To determine whether patients with the clinical phenotype of multifocal motor neuropathy but without the electrophysiological criteria for conduction block would respond to intravenous immunoglobulin (IVIg). METHODS: Ten patients were selected with a slowly progressive, asymmetric, lower motor neuron disorder, and were treated prospectively with IVIg at a dose of 2g/kg over 5 days. All subjects had neurophysiological testing to look for evidence of conduction block before treatment. Muscle strength was assessed by MRC grades and hand held myometry, measuring pinch and grip strength. A 20% increase in both pinch and grip myometry was considered a positive response. RESULTS: In no patient was conduction block detected. Four of the 10 patients showed a positive response to IVIg, with the best response occurring in two patients who presented with weakness but without severe muscle wasting. Three of the four responders have continued to receive IVIg for a mean period of 17 months (range 15-24 months), with continued effect. The response to IVIg was not related to the presence of anti-GM1 antiganglioside antibodies, but responders had a selective pattern of muscle weakness and normal (>90% predicted) vital capacity. CONCLUSION: The findings suggest that a course of IVIg should be considered in patients with the clinical phenotype of multifocal motor neuropathy but without neurophysiological evidence of conduction block.

Adult↗
PubMed1998

Chylous ascites: a manifestation of blunt abdominal trauma in an infant.

This report presents an infant in whom a unique case of chylous ascites developed after blunt abdominal trauma. Unfortunately, this case was complicated by Pseudomonas peritonitis, likely from a distant source. Our patient was treated medically and had a good overall outcome.

Abdominal Injuries↗
PubMed1998

Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?

There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.

Adolescent↗
PubMed1998

A proton magnetic resonance spectroscopic study in ALS: correlation with clinical findings.

OBJECTIVE: To evaluate neuronal dysfunction in the motor region subcortical white matter in ALS using volumetric localized proton magnetic resonance spectroscopy (1H-MRS). METHODS: Sixteen patients with E1 Escorial definite, probable, or possible ALS and eight healthy age-matched control subjects were studied. The ALS patients were divided into those with limb onset (n = 8) and those with bulbar onset (n = 8). Measurements of the metabolic ratios N-acetylaspartate (NAA)/creatine and phosphocreatine (Cr+PCr), NAA/choline (Cho), and Cho/(Cr+PCr) were correlated with clinical assessments. RESULTS: We found no differences in the metabolic peak area ratios in the motor region when comparing the total ALS group and the control subjects. However, correlations were found between the NAA/(Cr+PCr) ratio and the E1 Escorial category (p = 0.03), the ALS severity scale (p = 0.01), and the Medical Research Council score (p = 0.06). No correlations were found between the NAA/(Cr+PCr) ratio and the Ashworth Spasticity Scale, reflex score, or disease duration (p > 0.16). Bulbar-onset patients had a lower NAA/(Cr+PCr) ratio in the motor region compared with limb-onset patients (p = 0.03). CONCLUSION: In vivo 1H-MRS of the subcortical white matter in the motor region is unlikely to be sensitive enough to detect early disease changes in ALS because there is considerable overlap between the metabolic peak area ratios from patients with ALS and normal control subjects. However, changes in the NAA/(Cr+PCr) metabolic peak area ratios correlate with clinical measures of disease severity, and this measure may be useful in monitoring disease progression.

Adult↗
PubMed1997

Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson's disease: a proton magnetic resonance spectroscopy study.

We have carried out single-voxel proton magnetic resonance spectroscopy centered on the putamen both ipsilateral and contralateral to the worst affected side in nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine + Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant reduction in NAA/Cho ratios from the putamen contralateral to the most affected side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups compared with controls. There were no significant differences in NAA/(Cr + PCr) or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may reflect loss of nigrostriatal dopamine terminals or alternatively indicate a functional abnormality of striatal putaminal neurons, such as membrane dysfunction due to striatal deafferentation. This study suggests that NAA/Cho ratios may be affected by L-dopa therapy and this may provide a reversible marker of neuronal dysfunction in the striatum.

Adult↗
PubMed1996

Melatonin and insomnia.

The hypnotic action of melatonin 5 mg p.o. was explored in 15 subjects with psychophysiological insomnia in a double-blind controlled self-report questionnaire study. Melatonin or placebo was taken at 20.00 hours for a 1-week period in random order. Effects on sleep and wakefulness were monitored by visual analogue scale and structured interview. Bedtime, sleep onset time, estimated total sleep and wake time, as well as self-rated sleep quality, were not altered by melatonin, and estimates of next-day function did not change. The period of melatonin, treatment was retrospectively correctly identified by 8 of 15 subjects. Despite unchanged ratings of night sleep quality on the last night of each treatment, 7 of 15 subjects reported that sleep had subjectively improved to a minor extent in the week of active treatment. Side-effects attributed to melatonin included headache and an odd taste in the mouth. These data indicate that melatonin is probably of no clinical value in the management of psychophysiological insomnia.

Adult↗