Search PubMed⌕ Search

Biomedical subjects

T Ernst

Publications and source records attributed to T Ernst.

At least 37 records · Page 2Linked to original sources
PubMed2001

Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy.

Acquired deficiency of factor X occurs in patients with systemic amyloid light-chain (AL) amyloidosis, presumably due to adsorption of factor X to amyloid fibrils. Of 368 consecutive patients with systemic AL amyloidosis evaluated at Boston Medical Center, 32 patients (8.7%) had factor X levels below 50% of normal. Eighteen of these patients (56%) had bleeding complications, which were more frequent and severe in the 12 patients below 25% of normal; 2 episodes were fatal. Ten factor X-deficient patients received high-dose melphalan chemotherapy followed by autologous stem cell transplantation. Of 7 patients alive 1 year after treatment, 4 had a complete hematologic response, and all 4 experienced improvement in their factor X levels. One of 2 additional patients with partial hematologic responses had improvement in factor X. Thus, aggressive treatment of the underlying plasma cell dyscrasia in AL amyloidosis can lead to the amelioration of amyloid-related factor X deficiency.

Amyloid↗
PubMed2001

Automatic scan prescription for brain MRI.

Diagnostic brain MRI scans are usually performed by trained medical technologists who manually prescribe the position and orientation of a scanning volume. In this study, a fully automatic computer algorithm is described which compensates for variable patient positioning and acquires brain MRI scans in a predefined reference orientation. The method involves acquiring a rapid water-only pilot scan, segmenting the brain surface, and matching it to a reference surface. The inverse matching transformation is then used to adapt a geometric description of the desired scanning volume, defined relative to the reference surface, to the current patient. Both pilot scan and processing are performed within 30 sec. The method was tested in 25 subjects, and consistently recovered orientation differences between the reference and each subject to within +/-5 degrees. Compared to manual prescription, automatic scan prescription promises many potential benefits, including reduced scan times, reproducible scan orientations along anatomically preferable orientations, and better reproducibility for longitudinal studies. Magn Reson Med 45:486-494, 2001.

Algorithms↗
PubMed2001

Biexponential modeling of multigradient-echo MRI data of the brain.

Functional MRI (fMRI) using fast multigradient-echo acquisition methods allows the quantitative determination of the relevant parameter T2*. Previously, the TE-dependent signal decay has been modeled with a monoexponential function despite the complex composition of the brain. In this study, biexponential modeling was used to evaluate the relaxation of brain parenchyma and blood separate from that of cerebrospinal fluid. Single-shot multigradient-echo data acquired with spiral or EPI techniques were analyzed. In phantom experiments the biexponential method proved to be accurate. Compared to the biexponential procedure, the monoexponential model overestimated T2* (72.2 msec vs. 65.3 msec) and underestimated DeltaT2* (2.96 msec vs. 3.19 msec) during visual stimulation. The biexponential method may allow intrinsic correction for partial volume effects due to cerebrospinal fluid. The activation-induced parameter changes are detected with a sensitivity equal to that of a monoexponential method. The resulting T2* and DeltaT2* values describe the experimental data more accurately.

Brain↗
PubMed2001

HIV-2 infection with cerebral toxoplasmosis and lymphomatoid granulomatosis.

A Nigerian man had acute onset of headache and vertigo due to a cerebellar mass. A brain biopsy of the mass revealed toxoplasmosis despite repeated negative HIV-1 serology. The presence of an opportunistic infection and his country of origin raised the suspicion for HIV-2; this was confirmed by positive HIV-2 serology. Despite his preliminary pathological diagnosis, results of physiological magnetic resonance imaging (MRI) (perfusion MRI and proton magnetic resonance spectroscopy) were not typical for toxoplasmosis. The lesion showed a biochemical and perfusion pattern that was intermediate for infectious and neoplastic processes. Further neuropathology confirmed a secondary diagnosis of lymphomatoid granulomatosis.

AIDS-Related Opportunistic Infections↗
PubMed2001

Segmentation of progressive multifocal leukoencephalopathy lesions in fluid-attenuated inversion recovery magnetic resonance imaging.

BACKGROUND AND PURPOSE: The authors compared the reproducibility of a manual and a semiautomated technique for the quantitation of white-matter lesions in magnetic resonance imaging (MRI). METHODS: Volumes of white-matter lesions were determined using fluid-attenuated inversion recovery MRI in 23 AIDS patients with progressive multifocal leukoencephalopathy. Manual outlining was compared to an automated method based on region growing and adaptive thresholding. RESULTS: Lesion volumes from the 2 methods correlated well (61 lesions, r = 0.99, P < 10(-4)), although the volumes differed substantially (12.8% +/- 13.7%). Interscan, intrasubject reproducibility was better for the automated than the manual method (2.9% +/- 3.2% vs 12.4% +/- 16.2% volume difference, P = .02). CONCLUSION: The automated algorithm appeared more reproducible, which renders it superior to the manual method for longitudinal studies.

AIDS-Related Opportunistic Infections↗
PubMed2001

Brain proton magnetic resonance spectroscopy and imaging in children exposed to cocaine in utero.

OBJECTIVE: The effects of prenatal cocaine exposure have been examined using neurobehavioral and brain structural evaluations; however, no study has examined the effects of prenatal cocaine on brain metabolism. Proton magnetic resonance spectroscopy ((1)H-MRS) is a noninvasive method to examine the biochemistry of various brain regions. The purpose of this study was to examine the possible neurotoxic effects of prenatal cocaine exposure on the developing brain using (1)H-MRS. METHODS: Cocaine-exposed children (n = 14) and age-matched unexposed control participants (n = 12) were evaluated with MRI and localized (1)H-MRS. Metabolite concentrations of N-acetyl-containing compounds (NA), total creatine (Cr), choline-containing compounds, myoinositol, and glutamate + glutamine were measured in the frontal white matter and striatum. RESULTS: Despite an absence of structural abnormalities in either group, children exposed to cocaine in utero had significantly higher Cr (+13%) in the frontal white matter. NA, primarily a measure of N-acetyl aspartate and neuronal content, was normal in both regions examined by (1)H-MRS. Normal NA suggests no significant neuronal loss or damage in the 2 brain regions examined in children exposed to cocaine prenatally. CONCLUSIONS: Consistent with findings in abstinent adult cocaine users, we found increased Cr in the frontal white matter, with normal NA in children exposed to cocaine. These findings suggest the need to investigate further possible abnormalities of energy metabolism in the brain of children exposed to cocaine in utero. In addition, this study demonstrates the feasibility of using (1)H-MRS to investigate the effects of prenatal drug exposure on the developing brain.

Aspartic Acid↗
PubMed2000

Cerebral perfusion abnormalities in abstinent cocaine abusers: a perfusion MRI and SPECT study.

Nuclear medicine studies found decreased regional cerebral blood flow (rCBF) in the cortex and deep gray matter of cocaine users. Perfusion magnetic resonance imaging (MRI), a non-radioactive technique, has not been applied to evaluate persistent rCBF abnormalities. Twenty-five abstinent cocaine users and 15 healthy subjects without a history of drug use were examined with perfusion MRI, using dynamic bolus-tracking, and single photon emission computed tomography (SPECT), using 133Xe-calibrated 99mTc-HMPAO. After coregistration of SPECT with MRI, the relative rCBF (from perfusion MRI and SPECT) and absolute rCBF (from SPECT) were determined in 10 brain regions in each hemisphere. There was a statistically significant interaction between drug use and brain region on SPECT alone (relative and absolute rCBF), and on SPECT and perfusion MRI combined, but not on perfusion MRI alone. There also was a significant interaction among gender, drug use, and brain region. Compared to the control subjects, cocaine users showed increased rCBF in the frontal white matter (+8.6%, P=0.02) and in the globus pallidus (+6.3%, P=0.05), and decreased rCBF in the putamen (-3.9%, P=0.04) and the temporal cortex (-2.4%, P=0.02). SPECT and perfusion MRI detect a regional pattern of rCBF abnormalities in cocaine users that is consistent across the two methods. The hypoperfusion in the cortex and deep gray matter of the cocaine users is consistent with previous results. The increased rCBF in the white matter of cocaine users may be due to the presence of reactive glia.

Adolescent↗
PubMed2000

Gender differences in the functional organization of the brain for working memory.

Gender differences in brain activation during working memory tasks were examined with fMRI. Seventeen right-handed subjects (nine males, eight females) were studied with four different verbal working memory tasks of varying difficulty using whole brain echo-planar fMRI. Consistent with prior studies, we observed activation of the lateral prefrontal cortices (LPFC), the parietal cortices (PC), and additionally, caudate activation in both sexes. The volume of activated brain tissue increased with increasing task difficulty. For all four tasks, the male subjects showed bilateral activation or right-sided dominance (LPFC, PC and caudate), whereas females showed activation predominantly in the left hemisphere. The task performance data demonstrated higher accuracy and slightly slower reaction times for the female subjects. Our results show a highly significant (p < 0.001) gender differences in the functional organization of the brain for working memory. These gender-specific differences in functional organization of the brain may be due to gender-differences in problem solving strategies or the neurodevelopment. Therefore, gender matching or stratification is required for studies of brain function using imaging techniques.

Adult↗
PubMed2000

Evidence for long-term neurotoxicity associated with methamphetamine abuse: A 1H MRS study.

OBJECTIVE: To determine whether proton MRS (1H MRS) can detect long-term metabolite abnormalities in abstinent methamphetamine users. BACKGROUND: Methamphetamine is toxic to dopaminergic and serotonergic neurons in rodents; however, little data are available on the toxic effects of methamphetamine on the human brain. METHODS: 1H MRS was performed in 26 abstinent methamphetamine abusers with a history of methamphetamine dependence (median total cumulative lifetime exposure, 3,640 g; median recency of last methamphetamine use, 4.25 months) and 24 healthy subjects without a history of drug abuse. Cerebral metabolite concentrations on 1H MRS were measured in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: The concentration of N-acetylaspartate ([NA]), a neuronal marker, was reduced significantly (-5 to -6%) in the basal ganglia and frontal white matter of methamphetamine users compared with control subjects. The frontal white matter [NA] correlated inversely with the logarithm of the lifetime methamphetamine use. The methamphetamine users also showed significantly reduced total creatine in the basal ganglia (-8%), and increased choline-containing compounds ([CHO], +13%) and myo-inositol ([MI], +11%) in the frontal grey matter. CONCLUSIONS: The reduced [NA] on 1H MRS provides evidence for long-term neuronal damage in abstinent methamphetamine users.

Adult↗
PubMed2000

Effect of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] on cerebral blood flow: a co-registered SPECT and MRI study.

3,4-methylenedioxymethamphetamine (MDMA), an illicit recreational drug, damages serotonergic nerve endings. Since the cerebrovasculature is regulated partly by the serotonergic system, MDMA may affect cerebral blood flow (CBF) in humans. We evaluated 21 abstinent recreational MDMA users and 21 age- and gender-matched healthy subjects with brain SPECT and MRI. Ten of the MDMA subjects also had repeat SPECT and MRI after receiving two doses of MDMA. Abstinent MDMA users showed no significantly different global or regional CBF (rCBF) compared to the control subjects. However, within 3 weeks after MDMA administration, rCBF remained decreased in the visual cortex, the caudate, the superior parietal and dorsolateral frontal regions compared to baseline rCBF. The decreased rCBF tended to be more pronounced in subjects who received the higher dosage of MDMA. Two subjects who were scanned at 2-3 months after MDMA administration showed increased rather than decreased rCBF. Low-dose recreational MDMA use does not cause detectable persistent rCBF changes in humans. The lack of long-term rCBF changes may be due to a non-significant effect of serotonergic deficits on rCBF, or regeneration of serotonergic nerve terminals. The subacute decrease in rCBF after MDMA administration may be due to the direct effect of MDMA on the serotonergic system or the indirect effects of its metabolites on the dopaminergic system; the preliminary data suggest these effects may be transient.

Adult↗
PubMed2000

Perfusion MRI detects rCBF abnormalities in early stages of HIV-cognitive motor complex.

OBJECTIVE: To evaluate patients with early HIV-cognitive motor complex (HIV-CMC) for possible regional cerebral blood flow (rCBF) abnormalities on perfusion MRI (pMRI). BACKGROUND: Nuclear medicine techniques have demonstrated global and focal cerebral perfusion abnormalities in patients with HIV dementia. Ultrafast pMRI enables the measurement of rCBF throughout the brain without the need to apply radioactive tracers or ionizing radiation. METHODS: pMRI was used to measure the rCBF in 19 patients with early stages of HIV-CMC and 15 healthy seronegative control subjects. The rCBF maps were registered to high-resolution anatomic MRI scans and transformed into Talairach space. Statistical analysis of the rCBF maps was performed with SPM96. RESULTS: Compared with the control subjects, the patients with HIV had statistically significantly decreased rCBF bilaterally in the inferior lateral frontal cortices (right: -15%, p < 0.002; left: -12%, p < 0.005) and in the inferior medial parietal brain region (-15%, p < 0.0009). In contrast, rCBF was increased bilaterally in the posterior inferior parietal white matter (right: +19%, p < 0.0001; left: + 17%, p < 0.001). Furthermore, rCBF abnormalities correlated significantly with clinical disease severity as measured by CD4 count, plasma viral load, Karnofsky score, and HIV dementia scale. DISCUSSION: Our results are consistent with previous findings from PET and SPECT studies. Furthermore, pMRI can detect rCBF abnormalities that correlate with disease severity in HIV-CMC. Because pMRI is more cost-effective, faster, and safer than nuclear medicine techniques for monitoring rCBF changes, pMRI may be more feasible for monitoring the effects of therapy for HIV-CMC.

AIDS Dementia Complex↗
PubMed2000

Perfusion MRI of the human brain with dynamic susceptibility contrast: gradient-echo versus spin-echo techniques.

In this study, spin-echo and gradient-echo-based perfusion magnetic resonance imaging (MRI) techniques are systematically compared with respect to their application in the human brain. Six healthy subjects were evaluated with both techniques consecutively and injected twice with a gadolinium-based contrast agent. In accordance with theoretical predictions and with previous animal experiments, the spin-echo-based technique shows a markedly reduced appearance of large vessels. The intersubject standard deviations of the two methods are similar but smaller for the spin-echo technique in small regions adjacent to large vessels. Therefore, the sensitivity of the two acquisition methods for evaluating pathologic abnormalities may be similar despite the higher contrast-to-noise ratio of the gradient-echo-based technique. The gray-to-white matter ratio of the regional cerebral blood flow of the spin-echo method is closer to previous nuclear medicine measurements than that of the gradient-echo method. Our measurements indicate that spin-echo-based perfusion MRI is more representative of capillary perfusion than gradient-echo measurements. J. Magn. Reson. Imaging 2000;12:381-387.

Adult↗
PubMed2000

Changes in cerebral metabolism are detected prior to perfusion changes in early HIV-CMC: A coregistered (1)H MRS and SPECT study.

Human immunodeficiency virus-cognitive motor complex (HIV-CMC), a common complication of the acquired immunodeficiency syndrome (AIDS), is characterized by progressive cognitive impairment and motor dysfunction. Functional imaging methods, such as single-photon emission computed tomography (SPECT) and proton magnetic resonance spectroscopy ((1)H-MRS), have been applied to assess the severity of brain injury. However, it is unclear which of these two methods is more sensitive in detecting brain abnormalities in patients with early HIV-CMC. Twenty-four HIV-CMC patients were compared with 34 healthy subjects; each had quantitative SPECT ((133)Xenon-calibrated (99m)Tc-HMPAO) and quantitative (1)H-MRS. Both modalities were co-registered in order to assess regional cerebral blood flow (rCBF) and metabolite concentrations within the same voxel of interest in four brain regions (midfrontal and midparietal gray matter, temporoparietal white matter, and basal ganglia). On SPECT, only the temporoparietal white matter showed a trend for decreased rCBF in HIV-CMC patients (-13%, P = 0.06). On MRS, HIV-CMC patients showed significantly reduced creatine concentration in the basal ganglia (-8%, P = 0.008), as well as increased myoinositol concentrations in the basal ganglia (+25%, P = 0.01) and the temporoparietal white matter (+18%, P = 0.08). There was no significant correlation between SPECT and MRS variables in the patients in any region. (1)H MRS showed abnormal neurochemistry in the basal ganglia, whereas rCBF on SPECT was normal in the same region. This finding suggests that metabolite concentrations on (1)H MRS are better surrogate markers than rCBF measurements with SPECT for the evaluation of brain injury in early HIV-CMC. J. Magn. Reson. Imaging 2000;12:859-865.

AIDS Dementia Complex↗
PubMed2000

Computer simulation evidence of the transient planar state during the homeotropic to focal conic transition in cholesteric liquid crystals

Previous experimental evidence has suggested the existence of a transient planar state during the transition from a homeotropic state to a focal conic state. This does not appear at first to be physically reasonable. Here we show a quantitative numerical model of this transition that shows the existence of the transient planar state and agrees well with measured data. We compared this simulation with two experimental samples: one with parallel boundary conditions, and one with perpendicular boundary conditions. Both samples had thickness to pitch ratios of 13.9. The agreement of the simulation with the experimental data gives further evidence that the system passes through the transient planar during the transition. Also shown here are preliminary results for the second part of the transition, the transition from the transient planar state to the focal conic state, that suggest a Helfrich-like undulation deformation.

Journal Article↗
PubMed2000

Pharmacokinetics of nelarabine and 9-beta-D-arabinofuranosyl guanine in pediatric and adult patients during a phase I study of nelarabine for the treatment of refractory hematologic malignancies.

PURPOSE: To characterize the pharmacokinetics of nelarabine (506U78), the water-soluble prodrug of 9-beta-D-arabinofuranosyl guanine (ara-G), and ara-G in pediatric and adult patients with refractory hematologic malignancies. Ara-G is phosphorylated within leukemic cells to form ara-G triphosphate (ara-GTP), which acts to terminate DNA chain elongation, resulting in cell death. PATIENTS AND METHODS: The pharmacokinetics of nelarabine and/or ara-G were evaluated in 71 patients (25 pediatric and 46 adult patients) on the first day of therapy. Blood was collected at specified times for the determination of plasma nelarabine and ara-G concentrations. RESULTS: There were no statistically significant differences in the pharmacokinetics of nelarabine between any of the groups of patients. The harmonic mean half-life (t1/2) of nelarabine in pediatric and adult patients was 14.1 minutes and 16.5 minutes, respectively. The maximum concentrations (C(max)) of ara-G occurred at or near the end of the nelarabine infusion. The C(max) of ara-G ranged from 11.6 micromol/L to 308.7 micromol/L at nelarabine doses of 5 to 75 mg/kg and was linearly related to the nelarabine dose. No statistically significant differences were noted for the pharmacokinetic parameter estimates of ara-G between adult male and female patients. In children versus adults, the dose-normalized C(max), time of the C(max), and the steady-state volume of distribution of ara-G were similar. However, the clearance of ara-G was higher in pediatric patients (0.312 L.h(-1).kg(-1)) as compared with adult patients (0. 213 L.h(-1).kg(-1)) (P <.001). The t1/2 of ara-G was shorter in pediatric patients as compared with adult patients (2.1 hours v 3.0 hours; P <.01). CONCLUSION: Nelarabine is an effective prodrug of ara-G, allowing systemic concentrations of ara-G that result in clinical activity.

Adolescent↗
PubMed1999

Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia.

OBJECTIVE: To determine whether cerebral metabolite abnormalities normalize with highly active antiretroviral therapy (HAART). BACKGROUND: Patients with HIV-cognitive motor complex (HIV-CMC) show cerebral metabolite abnormalities in the early stages of dementia. METHODS: Sixteen patients with HIV-CMC were evaluated before and after HAART, and compared with 15 HIV-negative healthy volunteers. Cerebral metabolite ratios and concentrations in the frontal lobe and basal ganglia were measured using proton MRS (1H MRS). RESULTS: In 14 of 16 patients who tolerated HAART, CD4 count increased by 133+/-101 cells/mm3 (p = 0.0003), HIV Dementia Scale score increased by 1.8+/-2.4 points (p = 0.02), and AIDS dementia complex (ADC) stage decreased by 0.54+/-0.54 points (p = 0.003). The initially increased choline/creatine (CHO/CR) reversed in the midfrontal cortex (-8.0%; p = 0.02) and in the basal ganglia (-14.7%; p = 0.01). The initially elevated myoinositol (MI)/CR and myoinositol concentration [MI] in the basal ganglia also decreased (MI/CR: -14.1%; p = 0.005; [MI]: 11.8%; p = 0.02), along with normalization of [MI] in the frontal white matter (11.4%; p = 0.05). Furthermore, the change in [MI] in the frontal white matter correlated with the change in CD4 count (r = -0.67, p = 0.03) and with the change in ADC stage (p = 0.04). CONCLUSIONS: HAART improves HIV-CMC in addition to systemic measures of HIV infection. 1H MRS detects improvement of brain injury measured by cerebral metabolites, particularly the glial marker [MI], in patients with early HIV-CMC after HAART. In addition, the degree of improvement in clinical severity of HIV-CMC is related to the degree of recovery with [MI].

AIDS Dementia Complex↗
PubMed1999

Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex.

OBJECTIVE: To investigate the relation between biochemical alterations and disease severity in HIV-cognitive motor complex (HIV-CMC). BACKGROUND: HIV-CMC encompasses both the milder form (HIV-minor cognitive motor disorder [HIV-MCMD]) and the more severe form (HIV-dementia). There is no validated marker to monitor disease severity noninvasively. METHODS: A total of 54 patients with HIV-CMC (20 with HIV-MCMD, 34 with HIV-dementia) and 29 seronegative healthy volunteers were evaluated for cerebral metabolite abnormalities using proton (1H) MRS in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: The three subject groups showed different concentrations of myoinositol (MI; p = 0.0005) and choline-containing compounds (CHO; p = 0.004) in the frontal white matter. HIV-dementia patients had metabolite changes in all three brain regions whereas HIV-MCMD patients had abnormalities in the frontal white matter only. HIV-CMC patients had elevated MI (p < 0.0001) and CHO (p = 0.004) levels with increasing AIDS dementia complex stage, and N-acetyl compounds (NA) were decreased only in moderate to severe stages of dementia. Furthermore, CD4 count and CSF viral load, but not plasma viral load, showed significant effects on cerebral metabolite concentrations, which in turn showed significant effects on the HIV-dementia scale. CONCLUSIONS: In early stages of HIV-CMC, frontal white matter showed evidence of glial proliferation (with elevated MI and CHO levels) and cell membrane injury (with increased CHO levels), but no significant neuronal injury (with normal NA concentrations). HIV-MCMD and HIV-dementia patients have different neurochemical abnormalities. Because these biochemical alterations are related to clinical disease severity, they may be useful surrogate markers for noninvasive quantitative assessment of brain injury in patients with HIV-CMC.

AIDS Dementia Complex↗