Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 127 records · Page 7Linked to original sources

PubMed2001

Search for the decay upsilon(1S) --> gammaeta(').

We report on a search for the radiative decay Upsilon(1S)-->gammaeta(') in 61.3 pb(-1) of data taken with the CLEO II detector at the Cornell Electron Storage Ring. Three decay chains were investigated, all involving eta(')-->pi(+)pi(-)eta, followed by eta-->gammagamma, eta-->pi(0)pi(0)pi(0), or eta-->pi(+)pi(-)pi(0). We find no candidate events in any of the three cases and set a combined upper limit of 1.6x10(-5) at 90% C.L., significantly smaller than the previous limit. We compare our result to other radiative Upsilon decays, to radiative J/psi decays, and to theoretical predictions.

Journal Article↗

PubMed2001

Fatigue is not associated with raised inflammatory markers in multiple sclerosis.

BACKGROUND: The pathogenesis of fatigue in patients with MS is poorly understood. OBJECTIVE: To test the hypothesis that fatigue in MS is related to inflammatory disease activity as measured by systemic markers of inflammation. METHODS: Fatigue as assessed by the Fatigue Questionnaire Scale (FQS) and Krupp's Fatigue Severity Scale (KFSS) was correlated with several inflammatory markers in 38 patients with MS (16 relapsing-remitting [RR; 7 of whom had benign MS), 9 secondary progressive [SP], 13 primary progressive [PP]). The markers included daily urinary neopterin excretion, a marker of interferon-gamma-activated macrophage activity, and serum C-reactive protein (CRP) and soluble intercellular adhesion molecule-1 (sICAM-1) levels. Urinary neopterin excretion was measured daily for 2 weeks. RESULTS: No correlation was found between urinary neopterin excretion, CRP, or sICAM-1 and the fatigue scores. However, patients with a raised serum CRP level had higher KFSS, but not FQS, scores than patients with normal CRP levels (KFSS, 50 +/- 8 vs 41 +/- 14, p = 0.05; FQS, 13 +/- 4 vs 11 +/- 5, p = NS). When assessed using the FQS, patients with RR and SP MS were more fatigued than patients with PP MS (RR = 12.5 [4 to 23] vs SP = 13 [8 to 18] vs PP = 9 [7 to 14], p = 0.02). The patients with benign MS were as fatigued as patients with nonbenign disease. CONCLUSION: The pathogenesis of fatigue in MS is complex and does not appear to be directly related to systemic markers of inflammatory disease activity. Interestingly, patients with PP MS were less fatigued than patients with RR disease.

Adult↗

PubMed2001

Rate measurement of D(0)-->K+pi(-)pi(0) and constraints on D(0) -- D(0) mixing.

We present an observation and time-integrated rate measurement of the decay D(0)-->K(+)pi(-)pi(0) produced in 9 fb(-1) of e(+)e(-) collisions near the Upsilon(4S) resonance. The signal is inconsistent with an upward fluctuation of the background by 4.9 standard deviations. We measured the time-integrated rate of D(0)-->K(+)pi(-)pi(0) normalized to the rate of D(0)-->K(+)pi(-)pi(0) to be 0.0043(+0.0011)(-0.0010) (stat)+/-0.0007 (syst). This decay can be produced by doubly Cabibbo-suppressed decays or by the D(0) evolving into a D(0) through mixing, followed by a Cabibbo-favored decay to K(+)pi(-)pi(0). We also found the CP asymmetry A = (9(+25)(-22))% be consistent with zero.

Journal Article↗

PubMed2001

Experimental investigation of the two-photon widths of the chi(c0) and the chi(c2) mesons.

Using 12.7 fb(-1) of data collected with the CLEO detector at CESR, we observed two-photon production of the cc states chi(c0) and chi(c2) in their decay to pi(+)pi(-)pi(+)pi(-). We measured gamma(gammagamma)(chi(c))xB(chi(c)-->pi(+)pi(-)pi(+)pi(-)) to be 75+/-13(stat)+/-8(syst) eV for the chi(c0) and 6.4+/-1.8(stat)+/-0.8(syst) eV for the chi(c2), implying gamma(gammagamma)(chi(c0)) = 3.76+/-0.65(stat)+/-0.41(syst)+/-1.69(br) keV and gamma(gammagamma)(chi(c2)) = 0.53+/-0.15(stat)+/-0.06(syst)+/-0.22(br) keV. Also, cancellation of dominant experimental and theoretical uncertainties permits a precise comparison of gamma(gammagamma)(chi(c0))/gamma(gammagamma)(chi(c2)), evaluated to be 7.4+/-2.4(stat)+/-0.5(syst)+/-0.9(br), with QCD-based predictions.

Journal Article↗

PubMed2001

Infratentorial hypointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis.

In multiple sclerosis (MS), hypointense lesions on T1-weighted magnetic resonance imaging are thought to represent areas of tissue disruption and axonal loss. In previous studies of MS patients, infratentorial T1 hypointense lesions were found to be rare. In MS patients selected to have chronic cerebellar ataxia, we have determined the extent of infratentorial T1 hypointense lesions and their relationship with disability. We recruited nine patients with chronic cerebellar ataxia due to MS. An expanded disability status scale (EDSS) assessment was performed on each. The patients' brains were then imaged with axial-oblique dual-echo fast spin-echo and contrast-enhanced T1-weighted conventional spin-echo sequences. The number and total volume of infratentorial high-signal lesions on T2-weighted images and infratentorial hypointense lesions on T1-weighted images were calculated by a blinded observer using a computer-assisted contouring technique. A total of 96 infratentorial high-signal lesions were present, of which 62 (64.6%) appeared isointense and 34 (35.4%) hypointense with respect to the surrounding brain substance on the T1-weighted images. There was a median of 3 (range 0-10) and median volume of 0.43 ml (range 0-0.85 ml) infratentorial T1 hypointense lesions per patient. The EDSS score correlated with both the number (r=0.68, p=0.043) and the volume per patient (r=0.89, p=0.001) of infratentorial T1 hypointense but not T2 high-signal lesions. Infratentorial T1 hypointense lesions are often seen in patients with MS and chronic cerebellar ataxia. They may play a significant role in the disability suffered by these patients.

Adolescent↗

PubMed2001

Study of tau decays to six pions and a neutrino.

The tau decays to six-pion final states have been studied with the CLEO detector at the Cornell Electron Storage Ring. The measured branching fractions are B(tau(-)-->2pi(-)pi(+)3pi(0)nu(tau)) = (2.2+/-0.3+/-0.4)x10(-4) and B(tau(-)-->3pi(-)2pi(+)pi(0)nu(tau)) = (1.7+/-0.2+/-0.2)x10(-4). A search for substructure in these decays shows that they are saturated by intermediate states with eta or omega mesons. We present the first observation of the decay tau(-)-->2pi(-)pi(+)omega(nu)tau and the branching fraction is measured to be (1.2+/-0.2+/-0.1)x10(-4). The measured branching fractions are in good agreement with the isospin expectations but somewhat below the conserved-vector-current predictions.

Journal Article↗

PubMed2001

Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations.

OBJECTIVE: To quantitatively investigate water diffusion changes in normal-appearing white matter (NAWM) and gray matter in patients with MS, and to evaluate whether these changes are correlated with clinical disability and disease duration. BACKGROUND: Diffusion tensor imaging provides quantitative information about the magnitude and directionality (anisotropy) of water diffusion in vivo and detects pathologic changes in MS brain tissue. METHODS: Diffusion tensor imaging was performed in 39 patients with MS and in 21 age-matched control subjects. Quantitative indices, including fractional anisotropy, volume ratio, and mean diffusivity, were obtained in 30 regions of interest located in normal-appearing basal ganglia, cerebellar gray matter, and supratentorial and infratentorial NAWM. RESULTS: Patients with MS showed significantly reduced anisotropy and a trend toward increased diffusivity in the infratentorial and supratentorial NAWM, and significantly increased anisotropy in the basal ganglia. In all patients with MS, both fractional anisotropy and mean diffusivity in the cerebral peduncles were inversely correlated with the Expanded Disability Status Scale and pyramidal functional scores. In patients with relapsing-remitting MS, there was a strong correlation between Expanded Disability Status Scale score and fractional anisotropy in both supratentorial and infratentorial NAWM. In primary and secondary progressive MS, disease duration correlated strongly with mean diffusivity in infratentorial NAWM and fractional anisotropy in the cerebral peduncles, respectively. CONCLUSION: The most striking finding of decreased fractional anisotropy in supratentorial and infratentorial NAWM and increased fractional anisotropy in basal ganglia may result from axonal degeneration due to fiber transection in remote focal lesions. Diffusion tensor imaging indices, in particular fractional anisotropy, appear sensitive to structural damage in NAWM that is associated with disability and progression in MS.

Adult↗

PubMed2001

Search for B --> tau(nu) and B --> K(nu)nu.

We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged B meson decays. We exclusively reconstruct the companion B decay to suppress background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x 10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(-4) at 90% confidence level.

Journal Article↗

PubMed2001

First observation of the decays B(0) --> D(-)p_p pi+ and B(0) --> D(-)p_n.

We report the first observation of exclusive decays of the type B-->D(*)N_NX, where N is a nucleon. Using a sample of 9.7x10(6)B_B pairs collected with the CLEO detector operating at the Cornell Electron Storage Ring, we measure the branching fractions B(B0-->D(*-)p_p pi(+)) = (6.5(+1.3)(-1.2)+/-1.0)x10(-4) and B(B0-->D(*-)p_n) = (14.5(+3.4)(-3.0)+/-2.7)x10(-4). Antineutrons are identified by their annihilation in the CsI electromagnetic calorimeter.

Journal Article↗

PubMed2001

Magnetisation transfer ratio histogram analysis of primary progressive and other multiple sclerosis subgroups.

INTRODUCTION: Global magnetisation transfer ration (MTR) histogram analysis in the brain offers a method for evaluating pathological change both as a result of lesions and microscopic changes in normal appearing tissues. METHODS: 39 controls and 83 MS patients (46 primary progressive, 11 benign, 10 relapsing-remitting, 16 secondary progressive) were studied to explore the relationship of six conventional MTR histogram parameters with MS clinical subgroups and disability. Principal component (PC) analysis, which makes use of all the histogram data, was also used to examine the relationship between the MTR histogram and disability. RESULTS: When primary progressive patients were compared to controls, there were abnormalities of average MTR, and MTR at the 25th, 50th and 75th percentile. Disabled relapsing onset patients exhibited abnormalities in the same four parameters. Benign and nondisabled relapsing onset patients exhibited no significant abnormalities. Modest correlations were observed between disability and individual MTR parameters in relapse onset but not primary progressive patients--PC analysis revealed stronger and significant associations with disability in both subgroups. (r=0.40 for primary progressive and r=0.51 for relapsing onset). CONCLUSION: A number of MTR parameters are abnormal in primary progressive MS. MTR abnormalities are seen in disabled patients, whether of relapsing or primary progressive onset. The improved correlation with disability obtained by PC analysis suggests a useful role of this method for following clinically relevant pathological changes depicted in the MTR histogram.

Adult↗

PubMed2001

First observation of the sigma(+)(c) baryon and a new measurement of the sigma(+)(c) mass.

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.

Journal Article↗

PubMed2001

Analysis of MTR histograms in multiple sclerosis using principal components and multiple discriminant analysis.

Magnetization transfer ratio (MTR) histograms have the potential to characterize subtle diffuse changes in multiple sclerosis (MS) and other white matter disease. A new method is described which gives improved correlation with the Expanded Disability Status Scale (EDSS). Classification of individual subjects into normal and MS subgroups is shown. Principal component analysis (PCA) and multiple discriminant analysis (MDA) are shown to give results superior to methods of MTR histogram analysis using traditional features such as peak height and peak location. Scatterplots confirm the improved separation between groups achieved using the MDA score. The histogram analysis provides a comparison of two classification approaches, based on PCA and MDA, to recognize differences between normal controls and the four different subgroups of MS disease (and all MS patients). Multiple linear regression of these PCs vs. EDSS established an MR-based measure of disease. Using a central 60-mm slab of brain tissue, the success rate of binary classification between control and MS subgroups using MDA was 75-95%, depending on which two groups were being compared. Multiple regression analysis of EDSS with the first three PCs as independent variables was significant (r = 0.83 for secondary progressive MS, and r = 0.80 for all MS patients).

Brain↗

PubMed2001

Asymmetrical activation of human visual cortex demonstrated by functional MRI with monocular stimulation.

We have demonstrated asymmetric activation patterns in the visual cortices of normal humans who have undergone functional MRI with monocular photic stimulation. The contralateral hemisphere is activated more strongly and to a greater spatial extent than the ipsilateral hemisphere when either eye is stimulated. This asymmetry can be explained by nasotemporal asymmetries which have been described in anatomical studies of the visual system in primates and humans. In part, the representation of the monocular crescent of the temporal hemifield of either eye, which exists only in the crossed projection, may explain this. In addition, within the binocular field, there is a biased crossed projection of nasal retinal ganglion cells which drive the contralateral ocular dominance columns in V1. Finally, the blind spot representation in the ipsilateral visual cortex may also contribute to the observed asymmetries. Our study may in effect provide a functional correlate of the anatomical asymmetries that have been observed in humans and animals.

Adult↗

PubMed2001

Detection of optic nerve atrophy following a single episode of unilateral optic neuritis by MRI using a fat-saturated short-echo fast FLAIR sequence.

We describe an MRI technique for quantifying optic nerve atrophy resulting from a single episode of unilateral optic neuritis. We imaged 17 patients, with a median time since onset of optic neuritis of 21 months (range 3-81 months), using a coronal-oblique fat-saturated short-echo fast fluid-attenuated inversion-recovery (sTE fFLAIR) sequence. The mean cross-sectional area of the intraorbital portion of the optic nerves was calculated by a blinded observer from five consecutive 3 mm slices from the orbital apex forwards using a semiautomated contouring technique and compared with data from 16 controls. The mean optic nerve area was 11.2 mm2 in the affected eye of the patients, 12.9 mm2 in the contralateral eye (P = 0.006 compared to the affected eye) and 12.8 mm2 in controls (P = 0.03 compared to the affected eyes). There was a significant negative correlation between disease duration and the size of the affected optic nerve (r = -0.59, P = 0.012). The measurement coefficient of variation was 4.8%. The sTE fFLAIR sequence enables measurement of optic nerve area with sufficient reproducibility to show optic nerve atrophy following a single episode of unilateral optic neuritis. The correlation of increasing optic nerve atrophy with disease duration would be consistent with ongoing axonal loss in a persistently demyelinated lesion, or Wallerian degeneration following axonal damage during the acute inflammatory phase.

Adult↗

PubMed2001

Improved interobserver agreement for visual detection of active T2 lesions on serial MR scans in multiple sclerosis using image registration.

The aim of this study was to analyse the effect of image registration on interobserver agreement in the visual detection of active multiple sclerosis (MS) lesions from serial magnetic resonance (MR) scans. T2W spin-echo MR scans (3-mm slices) of 16 MS patients participating in a treatment trial were selected. For each patient, two pairs of scans were used: an original (i. e., non-registered) and a registered pair. For the original pair, baseline and month 6 were used, and for the registered pair month 3 and 9. For registration an automatic matching algorithm based on Mutual Information was used. Six observers identified active lesions on both original and registered scans. Kappa values were calculated to assess interobserver agreement. Reslicing caused a slight blurring of the images, but near perfect registration. The kappa value of 0.35 +/- 0.07 for new lesions on original images improved to 0.62 (+/- 0.06) by registration (p = 0.004). For enlarging lesions on original images it was extremely poor (kappa 0.11 +/- 0.05), and did not benefit much by registration (kappa 0.20 +/- 0.11). Thus, image registration improved interobserver agreement for visual detection of new lesions. For enlarging lesions, registration improved agreement but still not to a satisfactory level.

Adult↗

PubMed2001

Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis.

The aim of this study was to assess whether mean serum levels of inflammatory markers when measured serially correlate with disease progression or putative MRI markers of axonal loss in a cohort of well-characterised multiple sclerosis (MS) patients. Serial serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide metabolites nitrate and nitrite (NOx), C-reactive protein (CRP), neopterin and tumour necrosis factor alpha (TNF-alpha) were measured in 29 MS patients, 13 with a relapsing remitting (RR) and 16 with a secondary progressive (SP) course, who were participating in a phase II clinical trial of anti-CD4 therapy. Short-term whole blood stimulated TNF-alpha production was also measured. Patients were studied 12 times over an 18-month period. MRI variables included the number and volume of Gd-enhancing lesions and the change in T2-hyperintense, T1-hypointense lesions and cerebral volume between the baseline and exit studies. Disease progression required a sustained change in the EDSS. There was no correlation between mean levels of inflammatory markers over the study period and disease progression or changes in any of the MRI measures. However, mean sICAM-1 levels from the first 6 months of the study were higher in patients who progressed during the study than in those that did not (443 (SD439) vs. 235 (SD162) ng/mL, p=0.05). Mean levels of NOx were significantly higher in patients with RR MS than in patients with SP disease (59.1 micromol/L (SD 12.8) vs. 48.7 micromol/L (SD 11.9), p=0.02). Patients with either a single relapse or no relapse had significantly higher NOx levels than to patients with multiple relapses during the 18 month follow-up (59.0 micromol/L (SD 12.3) vs. 47.9 micromol/L (SD 12.0), p=0.02). The mean levels of the other inflammatory markers did not correlate with disease course or relapse-rate. Serum levels of many inflammatory markers do not correlate with short-term disease progression. Some of the data suggest that the effects of inflammation on disease progression are delayed. In addition raised levels of serum nitric oxide metabolites are associated with a lower number of clinical relapses and a non-progressive disease course. These findings, although preliminary, pose interesting questions on the role of nitric oxide in the pathogenesis of MS. Inducible NO production in the early stages of the disease may be beneficial.

Adult↗

PubMed2001

T1 hypointensity of the spinal cord in multiple sclerosis.

It has recently been shown in multiple sclerosis (MS) that the volume of T1 hypointense lesions in the brain explains more of the variance in disability amongst patients than T2 lesion volume. T1 hypointense lesions may therefore represent areas of underlying pathology likely to be of functional significance, such as axonal loss. The spinal cord is a common area of involvement in MS and its dysfunction is likely to be responsible for much of the motor disability seen. Hence it serves as a useful model by which to examine the functional relevance of differing imaging sequences. We have therefore examined the relationship between T1 signal intensity in the spinal cord and disability in 60 patients with MS. We have also examined the relationship between T1 signal intensity and atrophy of the cord, as the latter is another potential marker of axonal loss. Sixty patients with MS underwent spinal cord imaging with a T1 weighted sequence to acquire axial sections of the cord at the C2 level. These sections were histogram matched to allow comparison of image intensity and a manual outlining technique was applied from which the mean cord intensity was calculated. Within the patient group there was a significant relationship between T1 signal intensity and disability as measured with the EDSS (r = -0.4, p < 0.005) and also between T1 signal intensity and atrophy (r = 0.36, p < 0.005). This study demonstrates that disability and atrophy are associated with a generalised reduction in cord signal on T1 weighted images. A lower T1 signal intensity in the spinal cord may be more pathologically specific than T2 hyperintensity and may represent underlying axonal loss, although gliosis and predominant white matter atrophy are alternative possibilities.

Adult↗

PubMed2001

A modified protocol to improve the detection of enhancing brain and spinal cord lesions in multiple sclerosis.

By detecting focal blood-brain barrier (BBB) breakdown, gadolinium (Gd-DTPA) contrast-enhanced T1-weighted magnetic resonance imaging (MRI) allows assessment of inflammatory activity in multiple sclerosis (MS) and provides a sensitive means of monitoring immunomodulatory therapies in exploratory trials. Serial monthly studies were performed in eight relapsing-remitting and eight secondary progressive patients to assess new and more sensitive techniques for enhanced MRI. Brain and spine imaging was carried out at 1.5-T on two occasions 24-72 h apart using a conventional imaging protocol with T1-weighted MRI at single-dose (0.1 mmol/kg) Gd-DTPA and a potentially more sensitive "modified" protocol with T1-weighted MRI at triple-dose (0.3 mmol/kg) Gd-DTPA (with addition of delay and magnetisation transfer presaturation for brain imaging). For each MRI protocol the total numbers of enhancing lesions (97 paired studies) and new enhancing lesions (81 paired studies) were assessed. The total number of enhancing lesions seen was 347/75 on conventional brain/cord MRI respectively, and 754/123 on modified brain/cord MRI. The respective numbers of new enhancing lesions were 168/40 on conventional and 276/71 on modified scans. Smaller increases were seen in the proportion of active scans using the modified protocol. Sample size calculations showed no reduction in sample sizes required for a parallel group study but a reduced sample size for crossover studies using the modified protocol; the addition of cord to brain imaging did not improve power for either trial design. A combined modified brain and cord imaging protocol markedly improves the detection of areas of focal BBB leakage in MS and may be useful in selected natural history studies. The modified brain protocol reduces sample size requirements for crossover studies but not necessarily for parallel design trials.

Adult↗