Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 37 records · Page 2Linked to original sources

PubMed2006

Increasing cord atrophy in early relapsing-remitting multiple sclerosis: a 3 year study.

OBJECTIVES: Previous studies have shown that upper cervical cord atrophy (UCCA) occurs in multiple sclerosis (MS), particularly in those disabled and with primary or secondary progressive disease. It is less clear how early it can be detected in relapsing-remitting (RR) MS, and whether early cord atrophy relates to the concurrent or future clinical course. METHODS: Twenty seven RR MS patients (median disease duration 1.7 years, in all cases <3 years from onset) were recruited along with 20 controls. They were followed for up to 3 years with a yearly assessment of UCCA and clinical function measured by the Expanded Disability Status Scale (EDSS) and MS Functional Composite Score (MSFC). Clinical and MRI correlations were investigated. Statistical models adjusted for covariates including total intracranial volume. RESULTS: Longitudinal analysis showed a significant decrease in UCCA in patients both within the patient cohort (p < 0.001) and in comparison with controls (p = 0.001). There was a significant increase in EDSS (p = 0.008) but no significant change in MSFC. The rate of UCCA loss did not correlate with clinical change or with change in brain volume. CONCLUSIONS: In summary, serial UCCA measurement detects the development of spinal cord atrophy in clinically early RR MS.

Adult↗

PubMed2005

Precision measurements of the timelike electromagnetic form factors of pion, kaon, and proton.

Using 20.7 pb(-1) of e(+)e(-) annihilation data taken at sq.rt(r) = 3.671 GeV with the CLEO-c detector, precision measurements of the electromagnetic form factors of the charged pion, charged kaon, and proton have been made for timelike momentum transfer of |Q(2)| = 13.48 GeV(2) by the reaction e(+)e(-) --> h(+)h(-). The measurements are the first ever with identified pions and kaons of |Q(2)| > 4 GeV(2), with the results F(13.48 GeV(2)) = 0.075 +/- 0.008(stat) +/- 0.005(syst) and F(K)(13.48 GeV(2)) = 0.063 +/- 0.004(stat) +/- 0.001(syst). The result for the proton, assuming G(p)(E) = G(p)(M), is G(p)(M)(13.48 GeV(2)) = 0.014 +/- 0.002(stat) +/- 0.001(syst), which is in agreement with earlier results.

Journal Article↗

PubMed2005

Metabolite changes in early relapsing-remitting multiple sclerosis. A two year follow-up study.

Previous in vivo proton magnetic resonance spectroscopic imaging ((1)H-MRSI) studies have found reduced levels of N-acetyl-aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal-appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by (1)H-MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N-acetyl-aspartyl-glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing-remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent (1)H-MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM. At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (-7%, p = 0.003), as well as in the CGM (-8.7%, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial (1)H-MRSI may be relatively less sensitive to progressive pathological tissue changes in early RRMS.

Adult↗

PubMed2005

Diffusion MRI in multiple sclerosis.

Diffusion imaging is a quantitative, MR-based technique potentially useful for the study of multiple sclerosis (MS), due to its increased pathologic specificity over conventional MRI and its ability to assess in vivo the presence of tissue damage occurring outside T2-visible lesions, i.e., in the so-called normal-appearing white and gray matter. The present review aims at critically summarizing the state-of-the-art and providing a background for the planning of future diffusion studies of MS. Several pieces of evidence suggest that diffusion-weighted and diffusion tensor MRI are sensitive to MS damage and able to detect its evolution over relatively short periods of time. Although a significant relationship between diffusion-weighted MRI findings and MS clinical disability was not found in the earliest studies, with improved diffusion imaging technology correlations between diffusion abnormalities and MS clinical aspects are now emerging. However, the best acquisition and postprocessing strategies for MS studies remain a matter of debate and the contribution of newer and more sophisticated techniques to diffusion tensor MRI investigations in MS needs to be further evaluated. Although changes in diffusion MRI indices reflect a net loss of structural organization, at present we can only speculate on their possible pathologic substrates in the MS brain. Postmortem studies correlating diffusion findings with histopathology of patients with MS are, therefore, also warranted.

Autopsy↗

PubMed2005

Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials.

BACKGROUND: Gadolinium enhancement is often used in randomized clinical trials to evaluate the efficacy of new drugs in multiple sclerosis (MS). Knowledge about predictors of enhancement status is important for the selection of patients for MRI monitored trials. METHODS: Data from 17 trials were available in anonymized format through the Sylvia Lawry Centre for MS Research. In an open part containing 1,328 (non primary progressive) patients, two logistic regression analyses were explored, including demographic, clinical, and MRI predictors. The authors examined the area under the curve (AUC) and the increase in positive predictive value (PPV). The final selection of models was validated in a closed part of 848 comparable patients. RESULTS: Age at onset, disease duration, and disease course (CIS/RR/SP) were important predictors from the multivariate models. Further, a multivariate model including T2 burden of disease was more predictive than one with only clinical predictors (AUC 0.719 vs 0.625, p < 0.001). For the model with T2 burden of disease, the PPV was 66.8%, compared to 58.5% for the model without (a priori chance 46.4%). These findings were unequivocally confirmed in the closed part of the database. CONCLUSION: Gadolinium status can be predicted by a set of baseline variables, certainly when T2 burden of disease is included. These findings may benefit the design and statistical power of future randomized clinical trials.

Adult↗

PubMed2005

Absolute branching fraction measurements of exclusive D+ semileptonic decays.

Using data collected at the psi(3770) resonance with the CLEO-c detector at the Cornell e+e- storage ring, we present improved measurements of the absolute branching fractions of D+decays to K0e+ve, pi0e+ve, K*0e+ve, and p0e+ve, and the first observation and absolute branching fraction measurement of D+ --> omega e+ve. We also report the most precise tests to date of isospin invariance in semileptonic D0 and D+ decays.

Journal Article↗

PubMed2005

Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis.

In established multiple sclerosis, magnetization transfer ratio (MTR) histograms reveal abnormalities of normal-appearing white matter (NAWM) and grey matter (NAGM). The aim of this study was to investigate for such abnormalities in a large cohort of patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Magnetization transfer imaging was performed on 100 patients (67 women, 33 men, median age 32 years) a mean of 19 weeks (SD 3.8, range 12-33 weeks) after symptom onset with a clinically isolated syndrome and in 50 healthy controls (34 women, 16 men, median age 32.5 years). SPM99 software was used to generate segmented NAWM and NAGM MTR maps. The volumes of T2 lesions, white matter and grey matter were calculated. Eighty-one patients were followed up clinically and with conventional MRI after 3 years (n = 61) or until they developed multiple sclerosis if this occurred sooner (n = 20). Multiple regression analysis was used to investigate differences between patients and controls with age, gender and volume measures as covariates to control for potential confounding effects. The MTR histograms for both NAWM and NAGM showed a reduction in the mean (NAWM, 38.14 versus 38.33, P = 0.001; NAGM 32.29 versus 32.50, P = 0.009; units in pu) and peak location, with a left shift in the histogram. Mean NAWM and NAGM MTR were also reduced in the patients who developed clinically definite multiple sclerosis and multiple sclerosis according to the McDonald criteria but not in the 24 patients with normal T2-weighted brain magnetic resonance imaging (MRI). MTR abnormalities occur in the NAWM and NAGM at the earliest clinical stages of multiple sclerosis.

Adult↗

PubMed2005

Observation of the hc(1P1) state of charmonium.

The h(c)((1)P(1)) state of charmonium has been observed in the reaction psi(2S) --> pi(0)h(c) --> (gammagamma)(gammaeta(c)) using 3.08 x10(6) psi(2S) decays recorded in the CLEO detector. Data have been analyzed both for the inclusive reaction, where the decay products of the eta(c) are not identified, and for exclusive reactions, in which eta(c) decays are reconstructed in seven hadronic decay channels. We find M(h(c)) = 3524.4 +/- 0.6 +/- 0.4 MeV which corresponds to a hyperfine splitting DeltaM(hf)(1P) triple-bond pi(0)h(c)) x B(h(c) --> gammaeta(c)) = (4.0 +/- 0.8 +/- 0.7) x 10(-4).

Journal Article↗

PubMed2005

Long-term clinical outcome of primary progressive MS: predictive value of clinical and MRI data.

The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2* lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.

Atrophy↗

PubMed2005

A longitudinal study of cognition in primary progressive multiple sclerosis.

There are few longitudinal studies of cognition in patients with multiple sclerosis, and the results of these studies remain inconclusive. No serial neuropsychological data of an exclusively primary progressive series are available. Cross-sectional analyses have revealed significant correlations between cognition and magnetic resonance imaging (MRI) parameters in primary progressive multiple sclerosis (PPMS). This study investigated cognitive and MRI change in 99 PPMS patients from five European centres for 2 years. They were assessed at 12 month intervals using the Brief Repeatable Battery, a reasoning test, and a measure of depression. The MRI parameters of T1 hypointensity load, T2 lesion load, and partial brain volume were also calculated at each time point. There were no significant differences between the mean cognitive scores of the patients at year 0 and year 2. However, one-third of the patients demonstrated absolute cognitive decline on individual test scores. Results indicated that initial cognitive status on entry into the study was a good predictor of cognitive ability at 2 years. There was only a small number of significant correlations between changes in cognition and changes on MRI, notably T1 hypointensity load with the two attentional tasks (r = -0.266, P = 0.017; r = -0.303, P = 0.012). It is probable that multiple factors underlie this weak relation between the cognitive and MRI measures.

Adult↗

PubMed2005

Modification of MRI criteria for multiple sclerosis in patients with clinically isolated syndromes.

BACKGROUND: The McDonald criteria include MRI evidence for dissemination in space and dissemination in time for the diagnosis of multiple sclerosis in young adult patients who present with clinically isolated syndromes (CIS) typical of the disease. Although a major advance, the criteria have limited sensitivity for making an early diagnosis. OBJECTIVE: To compare the performance of McDonald criteria and modified McDonald criteria for dissemination in space and time for assessing the development of clinically definite multiple sclerosis. METHODS: McDonald criteria were modified using the combination of a less stringent definition for dissemination in space and allowing a new T2 lesion per se after three months as evidence for dissemination in time. Modified and McDonald criteria were applied in 90 CIS patients at baseline and at three month follow up scans. RESULTS: Both criteria were highly specific (>90%) but the modified criteria were more sensitive (77% v 46%) and more accurate (86% v 73%). CONCLUSIONS: These modified criteria should be evaluated in other CIS cohorts.

Cohort Studies↗

PubMed2005

Identifying brain regions for integrative sensorimotor processing with ankle movements.

The objective of this study was to define cortical and subcortical structures activated during both active and passive movements of the ankle, which have a fundamental role in the physiology of locomotion, to improve our understanding of brain sensorimotor integration. Sixteen healthy subjects, all right-foot dominant, performed a dorsi-plantar flexion task of the foot using a custom-made wooden manipulandum, which enabled measurements of the movement amplitude. All subjects underwent a training session, which included surface electromyography, and were able to relax completely during passive movements. Patterns of activation during active and passive movements and differences between functional MRI (fMRI) responses for the two types of movement were assessed. Regions of common activation during the active and passive movements were identified by conjunction analysis. We found that passive movements activated cortical regions that were usually similar in location to those activated by active movements, although the extent of the activations was more limited with passive movements. Active movements of both feet generated greater activation than passive movements in some regions (such as the ipsilateral primary motor cortex) identified in previous studies as being important for motor planning. Common activations during active and passive movements were found not only in the contralateral primary motor and sensory cortices, but also in the premotor cortical regions (such as the bilateral rolandic operculum and contralateral supplementary motor area), and in the subcortical regions (such as the ipsilateral cerebellum and contralateral putamen), suggesting that these regions participate in sensorimotor integration for ankle movements. In future, similar fMRI studies using passive movements have potential to elucidate abnormalities of sensorimotor integration in central nervous system diseases that affect motor function.

Adult↗

PubMed2005

Branching fractions for psi(2S)-to-J/psi transitions.

We describe new measurements of the inclusive and exclusive branching fractions for psi(2S) transitions to J/psi using e(+)e(-) collision data collected with the CLEO detector operating at CESR. All branching fractions and ratios of branching fractions reported here represent either the most precise measurements to date or the first direct measurements. Indirectly and in combination with other CLEO measurements, we determine B(chi(cJ) --> gamma(J/psi)) and B[psi(2S) --> light hadrons].

Journal Article↗

PubMed2005

Improved measurement of the form factors in the decay lambda+c-->lambda + nue.

Using the CLEO detector at the Cornell Electron Storage Ring, we have studied the distribution of kinematic variables in the decay lambda(+)(c)lambda--> e(+)nu(e). By performing a four-dimensional maximum likelihood fit, we determine the form factor ratio, R= f(2)/f(1) = -0.31 +/- 0.05(stat) +/- 0.04(syst), the pole mass, M(pole) = [2.21 +/- 0.08(stat) +/- 0.14(syst)] GeV/c(2), and the decay asymmetry parameter of the lambda(+)(c), alpha (lambda(c)) = -0.86 +/-0.03(stat) +/- 0.02(syst), for q(2) = 0.67 (GeV/c(2))(2). We compare the angular distributions of the lambda(+)(c) and lambda(-)(c) and find no evidence for CP violation: A(lambda(c)) = (alpha(lambda(c)) + alpha (lambda(c)))/(alpha(lambda(c))-alpha(lambda(c))) = 0.00 +/- 0.03(stat) +/- 0.01(syst) +/- 0.02, where the third error is from the uncertainty in the world average of the CP-violating parameter, A(lambda), for ppi(-).

Journal Article↗

PubMed2005

Increasing normal-appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing-remitting multiple sclerosis.

Abnormalities within normal-appearing grey and white matter (NAGM and NAWM) occur early in the clinical course of multiple sclerosis (MS) and can be detected in-vivo using the magnetisation transfer ratio (MTR). To better characterize the rates of change in both tissues and to ascertain when such changes begin, we serially studied a cohort of minimally disabled, early relapsing-remitting MS patients, using NAGM and NAWM MTR histograms. Twenty-three patients with clinically definite early relapsing-remitting MS (mean disease duration at baseline 1.9 years), and 19 healthy controls were studied. A magnetisation transfer imaging sequence was acquired yearly for two years. Twenty-one patients and 10 controls completed followup. NAWM and NAGM MTR histograms were derived and mean MTR calculated. A hierarchical regression analysis, adjusting for brain parenchymal fraction,was used to assess MTR change over time. MS NAWM and NAGM MTR were significantly reduced in comparison with controls at baseline and, in patients, both measures decreased further during follow-up: (-0.10 pu/year, p=0.001 and -0.18 pu/year, p<0.001 respectively). The rate of MTR decrease was significantly greater in NAGM than NAWM (p=0.004). Under the assumption that such changes are linear, backward extrapolation of the observed rates of change suggested that NAWM abnormality began before symptom onset. We conclude that increasing MTR abnormalities in NAWM and NAGM are observed early in the course of relapsing-remitting MS. It is now important to investigate whether these measures are predictive of future disability, and consequently, whether MTR could be used as a surrogate marker in therapeutic trials.

Adult↗

PubMed2005

Gray and white matter volume changes in early RRMS: a 2-year longitudinal study.

BACKGROUND: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray matter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy. OBJECTIVES: To characterize the evolution of GM and WM volumes over 2 years, and their associations with lesion loads in a cohort of patients with clinically early RRMS. METHODS: Twenty-one patients with RRMS (mean age 37.5 years, mean disease duration from symptom onset 2.1 years) and 10 healthy control subjects (mean age 37.1 years) were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1- and 2-year follow-up. Brain parenchymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated. In subjects with MS, brain lesion loads were determined on conventional T2-weighted along with pre- and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint. RESULTS: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean -2.1% vs -1.0%, p = 0.044), while no change was seen in WMF over the same period (mean -0.09% vs +0.09%, p = 0.812). However, when the MS cohort was divided in half, dependent upon change in Gd-enhancing lesion load over 2 years (n = 20), a decrease in WMF was seen in the group (n = 10) with the largest decline in Gd volume, whereas WMF increased in the other half (n = 10) concurrent with a net increase in volume of Gd-enhancing lesions (difference between groups: p = 0.034). CONCLUSIONS: Increasing gray matter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM lesions appear to be related to volume changes in WM over this time period.

Adult↗

PubMed2005

Chronic inflammatory demyelinating polyradiculoneuropathy: MRI study of brain and spinal cord.

CNS demyelinating lesions have been reported in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). There are no studies of cord atrophy in CIDP. Ten patients with CIDP underwent brain and spinal cord MRI to investigate CNS demyelination and cord atrophy. No CNS demyelination was found, but the mean cervical cord area was significantly smaller in CIDP patients vs control subjects. Spinal cord atrophy may be related to degeneration secondary to axonal loss.

Adult↗

PubMed2005

Search for X(3872) in gammagamma fusion and radiative production at CLEO.

We report on a search for the recently reported X(3872) state using 15.1 fb(-1) of e(+)e(-) data taken in the sqrt[s] = 9.46-11.30 GeV region. Separate searches for the production of the X(3872) in untagged gammagamma fusion and e(+)e(-) annihilation following initial state radiation are made by taking advantage of the unique angular correlation between the leptons from the decay J/psi --> l(+)l(-) in X(3872) decay to pi(+)pi(-)J/psi. No signals are observed in either case, and 90% confidence upper limits are established as (2J+1)Gamma(gammagamma)(X(3872))B(X --> pi(+)pi(-)J/psi) < 12.9 eV and Gamma(ee)(X(3872))B(X- -> pi(+)pi(-)J/psi) < 8.3 eV.

Journal Article↗