Search PubMed⌕ Search

Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 91 records · Page 5Linked to original sources
PubMed2003

Stereotactic co-registration of magnetic resonance imaging and histopathology in post-mortem multiple sclerosis brain.

A number of groups have examined the pathological substrate of signal changes on magnetic resonance imaging (MRI) in post-mortem (PM) brain of patients with multiple sclerosis (MS). Such studies will benefit from using a standardized method to reliably co-register regions of interest on MRI and tissue specimens. We investigated the usefulness of a stereotactic navigation system for this purpose. We also addressed the sensitivity of different standard MRI sequences with regard to lesion conspicuity in PM MS brain. Post-mortem brains of eight patients with MS were studied. Formalin-fixed coronal slices were placed in the head frame of a stereotactic system. Proton density-, T2-weighted and fast fluid-attenuated inversion recovery (FLAIR) scans were obtained and visually matched with scans that had been previously obtained on the same, but fresh, specimens. Guided by the stereotactic target points, the dissection of the fixed specimens was performed. After processing the blocks for embedding in paraffin, sections were stained with haematoxylin-eosin and Luxol fast blue. T2-weighted MRI of fixed brain revealed 24 areas suspected to be MS lesions, all of which were confirmed histologically. Three of these lesions were not visible on macroscopic inspection. There were 14 additional hyperintensities on T2-weighted or FLAIR MRI of the fresh specimens, five of which did not correlate to MS lesions histologically. Stereotactic navigation is a useful approach to co-register MRI and histopathology in PM brain of MS patients and may improve the precision of MRI-guided sampling of tissue specimens. Standard T2-weighted MRI appeared to be the single most useful approach for lesion detection in fresh and fixed specimens.

Brain↗
PubMed2003

The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study.

BACKGROUND: Studies have suggested that T2 lesion activity is prominent in early relapsing-remitting multiple sclerosis, whereas brain atrophy, while seen early, appears more evident in later progressive disease. The temporal relation between these processes remains unclear. OBJECTIVE: To explore the association between changing brain lesion loads and subsequent tissue atrophy in multiple sclerosis. METHODS: 28 subjects with clinically probable or definite multiple sclerosis (mean age 46.0 years; 17 female and 11 male) were followed for 14 years after first onset of symptoms. T2 lesion loads were estimated soon after symptom onset and at around five, 10, and 14 years later. Disease related atrophy was estimated at the 14 year follow up by comparing brain tissue volumes (proportional to total intracranial volumes) determined in the multiple sclerosis group with data from 29 normal control subjects (mean age 36.7 years; 16 female, 13 male) using multiple linear regression analyses to allow for differences in age and sex distributions. RESULTS: Change in lesion load in the first five years was more closely correlated to disease related brain atrophy at 14 years than later changes in lesion load, although the correlation was only moderate (Spearman correlation = -0.528, p = 0.004). CONCLUSIONS: From this, it appears that early rather than later focal lesion accumulation relates to subsequent brain atrophy, but factors unconnected directly with lesion formation probably also play a significant role in determining such atrophy.

Adult↗
PubMed2003

Spinal cord MRI in clinically isolated optic neuritis.

BACKGROUND/METHODS: One hundred and fifteen patients with clinically isolated optic neuritis underwent magnetic resonance imaging (MRI) of the brain and spinal cord within 3 months of the onset of symptoms. RESULTS: Eighty one (70%) patients had brain lesions and 31 (27%) had cord lesions. Cord lesions were seen in 12% with a normal brain MRI, 21% with between one and eight brain lesions, and 45% with nine or more brain lesions. When the new diagnostic criteria for MS were applied, MRI cord imaging used for evidence of dissemination in time and space allowed a diagnosis of MS in only one additional asymptomatic patient at 1 year, two additional asymptomatic patients at 3 years. CONCLUSIONS: Using existing criteria, spinal cord imaging rarely contributes to the diagnosis in patients with clinically isolated optic neuritis.

Adolescent↗
PubMed2003

Interferon beta in multiple sclerosis: experience in a British specialist multiple sclerosis centre.

BACKGROUND: The efficacy of interferon beta (IFN beta) is well established in relapsing-remitting multiple sclerosis (MS). However, the use of this drug in clinical practice is complex, especially because it is only partially effective, its long term efficacy and side effects are unknown, its efficacy may be abrogated by the development of neutralising antibodies, compliance is variable, and its cost effectiveness is controversial. OBJECTIVES AND METHODS: Analysis of a prospectively followed up series of 101 MS patients treated with IFN beta was undertaken to: (1) monitor the outcome of IFN beta treatment in clinical practice; (2) compare the immunogenicity of the three commercial IFN beta preparations available; (3) assess the proportion of patients fulfilling the current guidelines of the Association of British Neurologists for stopping IFN beta therapy. RESULTS: During a median treatment period of 26 months (range 2-85), the relapse rate decreased by 41%. Although the reduction in the relapse rate was similar for all three commercial products, none of the Avonex treated patients were relapse free, compared with 19% of the Betaferon treated and 27% of the Rebif treated patients (p=0.02). Neutralising antibodies were not detected in Avonex treated patients (0 of 18), compared with 12 of 32 (38%) Betaferon treated and 10 of 23 (44%) Rebif treated patients (p=0.02). Forty of 101 (40%) patients satisfied the current (2001) Association of British Neurologists criteria for stopping IFN beta treatment at some stage during their treatment. CONCLUSION: IFN beta is effective in reducing the relapse rate in patients with relapsing-remitting MS in routine clinical practice. However, after a median treatment duration of 26 months, 40% of initially relapsing-remitting MS patients seem to have ongoing disease activity, presenting as disabling relapses or insidious progression.

Adjuvants, Immunologic↗
PubMed2003

Diffusion tensor imaging detects corticospinal tract involvement at multiple levels in amyotrophic lateral sclerosis.

BACKGROUND: Histopathological studies of amyotrophic lateral sclerosis (ALS) are of end stage disease. Diffusion tensor imaging (DTI) provides the opportunity to investigate indirectly corticospinal tract pathology of ALS in vivo. METHODS: DTI was used to study the water diffusion characteristics of the corticospinal tracts in 21 patients with ALS and 14 normal controls. The authors measured the fractional anisotropy (FA) and mean diffusivity (MD) along the pyramidal tracts from the internal capsules down to the pyramids. A mixed model regression analysis was used to compare FA and MD between the ALS and control groups. RESULTS: FA showed a downward linear trend from the cerebral peduncles to the pyramids and was lower in the ALS group than controls at multiple levels of the corticospinal tract. At the internal capsules, FA was higher on the right. MD showed an upward trend, progressing caudally from the internal capsules to the pyramids. MD was higher at the level of the internal capsule in the ALS group, but caudally this difference was not maintained. No correlations were found between clinical markers of disability and water diffusion indices. CONCLUSIONS: These findings provide insights into the pathological processes of ALS. Differences in diffusion characteristics at different anatomical levels may relate to underlying tract architecture or the distribution of pathological damage in ALS. Further development may permit monitoring of progression and treatment of disease.

Adult↗
PubMed2003

Preliminary magnetic resonance study of the macromolecular proton fraction in white matter: a potential marker of myelin?

We report on a new quantitative magnetization transfer (MT) technique that allows for the in vivo estimation of the macromolecular proton fraction (f) and the bound pool T2 relaxation time (T2b), whilst permitting whole brain coverage. In this pilot study, five subjects with multiple sclerosis (MS) and five healthy controls were studied. Both f and T2b were significantly different between MS lesions and normal control white matter (WM). Relationships between f and T1 relaxation time [Spearmans rank correlation coefficient (r(s)) = -0.97, P < 0.001] and f and the magnetization transfer ratio (MTR; r(s) = 0.80, P < 0.001) were observed. Compared with MTR, f and T2b have the potential advantage of relative independence from MT acquisition protocol while offering more pathologically specific information. In particular, f may provide a more direct indication of myelin content in WM.

Adult↗
PubMed2003

Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities.

BACKGROUND: Magnetization transfer ratio (MTR) histogram analysis provides a global measure of disease burden in multiple sclerosis (MS). MTR abnormalities in normal appearing brain tissue (NABT) provide quantitative information on the extent of tissue damage undetected by conventional T2-weighted (T2W) magnetic resonance imaging (MRI). AIMS: 1) To compare the MTR histograms from NABT across a broad spectrum of relapse onset MS patients, including relapsing-remitting (RR) MS (including newly diagnosed and benign subgroups) and secondary progressive (SP) MS. 2) To determine the relationship between clinical disability and NABT MTR histograms. METHODS: 2D spin echo magnetization transfer imaging was performed on 70 RRMS and 25 SPMS patients and compared with 63 controls. MTR histograms were acquired for NABT after extracting lesions and cerebrospinal fluid (CSF). T2W images were used to measure the brain parenchymal fraction (BPF) and T2 lesion load. RESULTS: MS patients had a disease duration ranging from 0.5 to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 8.5. There was a significant decrease in NABT mean MTR (+/- standard deviation) compared with controls (33.07 pu +/- 1.06 versus 34.26 pu +/- 0.47; P < 0.001) with an effect size of 2.56. The reduction in NABT mean MTR varied among patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5% for benign MS, compared with controls. NABT mean MTR correlated significantly with T2 lesion load (r = -0.82) and BPF (r = 0.58). EDSS score correlated with NABT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r = 0.59). Multivariate analysis using NABT MTR peak height, T2 lesion load and BPF combined only accounted for 38% of the variance in the EDSS (r = 0.62; P < 0.001). Disease duration accounted for an additional 14% of variance in the EDSS (r = 0.72; P < 0.001). CONCLUSIONS: There is evidence of diffuse abnormalities in NABT in addition to global brain atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and benign MS. The abnormalities are greatest in patients with the more disabling SPMS. Atrophy, NABT and lesion abnormalities are all partly correlated; the processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.

Adult↗
PubMed2002

Measurements of inclusive B-->psi production.

Using the combined CLEO II and CLEO II.V data sets of 9.1 fb(-1) at the Upsilon(4S), we measure properties of psi mesons produced directly from decays of the B meson, where "B" denotes an admixture of B+, B-, B0, and B;(0), and "psi" denotes either J/psi(1S) or psi(2S). We report first measurements of psi polarization in B-->psi(direct)X: alpha(psi(1S))=-0.30(+0.07)(-0.06)+/-0.04 and alpha(psi(2S))=-0.45(+0.22)(-0.19)+/-0.04. We also report improved measurements of the momentum distributions of psi produced directly from B decays, correcting for measurement smearing. Finally, we report measurements of the inclusive branching fraction for B-->psiX and B-->chi(c1)X.

Journal Article↗
PubMed2002

Management of acute optic neuritis.

Optic neuritis is a common condition that causes reversible loss of vision. It can be clinically isolated or can arise as one of the manifestations of multiple sclerosis. Occasional cases are due to other causes, and in these instances management can differ radically. The treatment of optic neuritis has been investigated in several trials, the results of which have shown that corticosteroids speed up the recovery of vision without affecting the final visual outcome. Other aspects of management, however, are controversial, and there is uncertainty about when to investigate and when to treat the condition. Here we review the diagnostic features of optic neuritis, its differential diagnosis, and give practical guidance about management of patients. The condition's association with multiple sclerosis will be considered in the light of studies that define the risk for development of multiple sclerosis and with respect to results of trials of disease-modifying drugs in these individuals.

Adrenal Cortex Hormones↗
PubMed2002

Dalitz analysis of D0-->K(0)(S)pi(+)pi(-).

In e(+)e(-) collisions using the CLEO detector, we have studied the decay of the D0 to the final state K(0)(S)pi(+)pi(-) with the initial flavor of the D0 tagged by the decay D(*+)-->D0pi(+). We use the Dalitz technique to measure the resonant substructure in this final state and clearly observe ten different contributions by fitting for their amplitudes and relative phases. We observe a K(*)(892)(+)pi(-) component which arises from doubly Cabibbo suppressed decays or D0-D0; mixing.

Journal Article↗
PubMed2002

Observation of B-->K(0)(S)pi(+)pi(-) and Evidence for B-->K(*+/-)pi(-/+).

We report on a search for charmless hadronic B decays to the three-body final states K(0)(S)h(+)pi(-), K(+)h(-)pi(0), K(0)(S)h(+)pi(0) (h(+/-) denotes a charged pion or kaon), and their charge conjugates, using 13.5 fb(-1) of integrated luminosity produced near sqrt[s]=10.6 GeV, and collected with the CLEO detector. We observe the decay B-->K0pi(+)pi(-) with a branching fraction (50(+10)(-9)(stat.)+/-7(syst.))x10(-6) and the decay B-->K(*+)(892)pi(-) with a branching fraction (16(+6)(-5)(stat.)+/-2(syst.))x10(-6).

Journal Article↗
PubMed2002

Measurement of B(D+-->K(*0)l(+)nu(l)).

Using 13.53 fb(-1) of CLEO data, we have measured the ratios of the branching fractions R(+)(e),R(+)(mu) and the combined branching fraction ratio R(+)(l), defined by R(+)(l)=[B(D+-->K(*0)l(+)nu(l))]/[B(D+-->K-pi(+)pi(+))]. We find R(+)(e)=0.74+/-0.04+/-0.05, R(+)(mu)=0.72+/-0.10+/-0.05, and R(+)(l)=0.74+/-0.04+/-0.05, where the first and second errors are statistical and systematic, respectively. The known branching fraction B(D+-->K-pi(+)pi(+)) leads to B(D+-->K(*0)e(+)nu(e))=(6.7+/-0.4+/-0.5+/-0.4)%, B(D+-->K(*0)mu(+)nu(mu))=(6.5+/-0.9+/-0.5+/-0.4)%, and B(D+-->K(*0)l(+)nu(l))=(6.7+/-0.4+/-0.5+/-0.4)%, where the third error is due to the uncertainty in B(D+-->K-pi(+)pi(+)).

Journal Article↗
PubMed2002

Observation of the decay Omega(0)(c)-->Omega(-)e(+)nu(e).

Using the CLEO detector at the Cornell Electron Storage Ring we have observed the Omega(0)(c) (css ground state) in the decay Omega(0)(c)-->Omega(-)e(+)nu(e). We find a signal of 11.4+/-3.8(stat) events. The probability that we have observed a background fluctuation is 7.6x10(-5). We measure B(Omega(0)(c)-->Omega(-)e(+)nu(e)).sigma(e(+)e(-)-->Omega(0)(c)X)=(42.2+/-14.1(stat)+/-5.7(syst)) fb and R=[Gamma(Omega(0)(c)-->Omega(-)pi(+))]/[Gamma(Omega(0)(c)-->Omega(-)enu(e))]=00.41+/-0.19(stat)+/-0.04(syst). This is the first statistically significant observation of an individual decay mode of the Omega(0)(c) in e(+)e(-) annihilation and the first example of a baryon decaying via beta emission, where no quarks from the first generation participate in the reaction.

Journal Article↗
PubMed2002

Functional magnetic resonance imaging of the cortical response to photic stimulation in humans following optic neuritis recovery.

Recovery from optic neuritis has been shown to be associated with an abnormal functional MRI (fMRI) response following exposure of the eye to an epoch based (ON-OFF design) flickering photic stimulus. Visual cortex activation is reduced during photic stimulation, whilst extra-occipital areas are extensively activated with a peak blood oxygen level dependent response during the OFF phase of the stimulus paradigm. We performed a further fMRI experiment to determine whether the abnormal extra-occipital response is a phase-specific phenomenon or whether it results from a delayed haemodynamic response. A cohort of patients that recovered from optic neuritis was studied, this time using a longer photic stimulation epoch (40 s). The extra-occipital response again peaked during the baseline condition, indicating that the phenomenon is phase dependent. Our results also reinforce the important findings of extra-occipital activation following optic neuritis which may represent an adaptive reorganization of the cerebral response.

Adult↗
PubMed2002

Normal-appearing brain tissue MTR histograms in clinically isolated syndromes suggestive of MS.

Segmented normal-appearing brain tissue (NABT) was investigated in 40 patients with a recent onset and 13 patients with a remote onset of a clinically isolated syndrome (CIS) using magnetization transfer ratio (MTR) histograms. Abnormalities were present in patients with a high risk for MS (recent onset and T2-weighted lesions present) and in those with a low risk for relapse (recent onset without T2-weighted lesions). Similar mild NABT abnormality was present with CIS and no further disease activity 14 years later. NABT MTR abnormality in CIS may indicate susceptibility to demyelination but not to disease progression.

Adult↗
PubMed2002

Investigating regional white matter in schizophrenia using diffusion tensor imaging.

Diffusion tensor imaging (DTI) was used to investigate regional white matter in vivo in patients with schizophrenia. DTI is capable of providing information about the organization of white matter tracts and has only recently been used to study schizophrenia. In this study, a voxel based analysis of DTI maps in 14 patients and 19 controls did not reveal any areas of significant differences in DTI measures in white matter. The findings suggest that the structural integrity of white matter in these patients was not disrupted. These results are discussed in relation to previous studies reporting positive findings. It is concluded that further studies using DTI in larger samples, improved and standardised methods of data acquisition and analysis are needed.

Adult↗