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Biomedical subjects

Thomas Ernst

Publications and source records attributed to Thomas Ernst.

12 recordsLinked to original sources
PubMed2004

Efficacy and cardiovascular tolerability of extended dialysis in critically ill patients: a randomized controlled study.

BACKGROUND: Extended dialysis is an increasingly used modality of renal replacement therapy that theoretically offers advantages of both intermittent and continuous therapies in the intensive care unit (ICU). METHODS: We randomly treated 39 ventilated critically ill patients with oliguric acute renal failure with either continuous venovenous hemofiltration (CVVH; n = 19; age, 50.1 +/- 3.2 years; Acute Physiology and Chronic Health Assessment II [APACHE II] score, 32.3 +/- 1.2; 79% sepsis) and a substitution fluid rate of at least 30 mL/kg/h for 24 hours or with extended dialysis for 12 hours (n = 20; age, 50.8 +/- 3.6 years; APACHE II score, 33.6 +/- 1.0; 85% sepsis). The latter was performed using an easy-to-handle, single-pass, batch dialysis system. All hemodynamic parameters were monitored invasively by means of an indwelling arterial catheter. RESULTS: Average mean arterial blood pressure, heart rate, cardiac output, systemic vascular resistance, and catecholamine dose were not significantly different in both therapies. Urea reduction rate was similar with extended dialysis compared with CVVH therapy (53% +/- 2% versus 52% +/- 3%; P = not significant) despite an average rate of substitution fluid with the latter of 3.2 +/- 0.1 L/h. This was corroborated by the finding of similar amounts of urea eliminated in the collected spent total hemofiltration and dialysis fluid. Correction of acidosis was accomplished faster with extended dialysis than CVVH, and the amount of heparin used was significantly lower with extended dialysis (P < 0.01). CONCLUSION: Extended dialysis combines excellent detoxification with cardiovascular tolerability, even in severely ill patients in the ICU. The technically simple dialysis system used offers flexibility of treatment time.

APACHE↗
PubMed2003

A multi-center 1H MRS study of the AIDS dementia complex: validation and preliminary analysis.

PURPOSE: To demonstrate the technical feasibility and reliability of a multi-center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N-acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC). MATERIALS AND METHODS: Using an automated protocol (GE PROBE-P), short echo time spectra (TE = 35 msec) were obtained at eight sites from uniformly prepared phantoms and from three brain regions (frontal white matter, basal ganglia, and parietal cortex) of normal volunteers and ADC and HIV-negative subjects. RESULTS: A random-effects model of the phantom and volunteer data showed no significant inter-site differences. Feasibility of a multi-center study was further validated by detection of significant differences between the metabolite ratios of ADC subjects and HIV-negative controls. ADC subjects exhibited significantly higher Cho/Cr and MI/Cr in the basal ganglia and significantly reduced NAA/Cr and significantly higher MI/Cr in the frontal white matter. These results are consistent with the predominantly subcortical distribution of the pathologic abnormalities associated with ADC. CONCLUSION: This is the first study to ascertain and validate the reliability and reproducibility of a short echo time (1)H-MRS acquisition sequence from multiple brain regions in a multi-center setting. It should now be possible to examine the regional effects of HIV infection in the brain in a large number of subjects and to study the metabolic effects of new therapies for the treatment of ADC in a clinical trial setting.

AIDS Dementia Complex↗
PubMed2003

Echo planar imaging at 4 Tesla with minimum acoustic noise.

PURPOSE: To minimize the acoustic sound pressure levels of single-shot echo planar imaging (EPI) acquisitions on high magnetic field MRI scanners. MATERIALS AND METHODS: The resonance frequencies of gradient coil vibrations, which depend on the coil length and the elastic properties of the materials in the coil assembly, were measured using piezoelectric transducers. The frequency of the EPI-readout train was adjusted to avoid the frequency ranges of mechanical resonances. RESULTS: Our MRI system exhibited two sharp mechanical resonances (at 720 and 1220 Hz) that can increase vibrational amplitudes up to six-fold. A small adjustment of the EPI-readout frequency made it possible to reduce the sound pressure level of EPI-based perfusion and functional MRI scans by 12 dB. CONCLUSION: Normal vibrational modes of MRI gradient coils can dramatically increase the sound pressure levels during echo planar imaging (EPI) scans. To minimize acoustic noise, the frequency of EPI-readout trains and the resonance frequencies of gradient coil vibrations need to be different.

Acoustics↗
PubMed2003

Prometheus--a new extracorporeal system for the treatment of liver failure.

BACKGROUND/AIMS: Extracorporeal detoxification systems for supportive therapy of liver failure have recently gained much interest. We herein report results from the first clinical application of Prometheus, a new liver support system in which albumin-bound substances are directly removed from blood by special adsorber. In a simultaneous step, high-flux hemodialysis is performed. We assessed safety, adsorber efficiency and clinical efficacy of the Prometheus system. METHODS: Eleven patients with acute-on-chronic liver failure and accompanying renal failure were treated with Prometheus on 2 consecutive days for >4 h. RESULTS: Prometheus treatment significantly improved serum levels of conjugated bilirubin, bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. There were no significant changes in hemoglobin and platelet levels, whereas leucocytes increased without signs of systemic infection. No treatment-related complications except a blood pressure drop in two patients with systemic infection were noted. In one patient (Child-Pugh score: 15) Prometheus treatment could not be completed due to onset of uncontrolled bleeding 16 h after dialysis. CONCLUSIONS: Prometheus is a safe supportive therapy for patients with liver failure. A significant improvement of the biochemical milieu was observed already after two treatments. Prospective controlled studies with the Prometheus system are necessary to evaluate hard clinical end-points.

Adult↗
PubMed2003

k-Space based summary motion detection for functional magnetic resonance imaging.

Functional MRI studies are very sensitive to motion; head movements of as little as 1-mm translations or 1 degrees rotations may cause spurious signals. An algorithm was developed that uses k-space MRI data to monitor subject motion during functional MRI time series. A k-space weighted average of squared difference between the initial scan and subsequent scans is calculated, which summarizes subject motion in a single quality parameter; however, the quality parameter cannot be used for motion correction. The evolution of this quality parameter throughout a time series indicates whether head motion is within a predetermined limit. Fifty functional MRI studies were used to calibrate the sensitivity of the algorithm, using the six rigid-body registration parameters (three translations and three rotations) from the statistical parametric mapping (SPM99) package as a reference. The average correlation coefficient between the new quality parameter and the reference value from SPM was 0.84. The simple algorithm correctly classified acceptable or excessive motion with 90% accuracy, with the remaining 10% being borderline cases. This method makes it possible to evaluate brain motion within seconds after a scan and to decide whether a study needs to be repeated.

Algorithms↗
PubMed2003

Magnetic resonance spectroscopy studies of GABA in neuropsychiatric disorders.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and is integral to managing brain excitability. GABA concentrations vary according to age, gender, and brain region. Magnetic resonance spectroscopy (MRS), with editing or with localized 2-dimensional chemical shift methods, can measure GABA levels in vivo, ex vivo, or in vitro, particularly at ultra-high magnetic field strengths. Proton ((1)H) MRS studies have found reduced or abnormal GABA concentrations in several neuropsychiatric disorders, including epilepsy, anxiety disorders, major depression, and drug addiction. Disorders with low GABA levels may be treated by augmentation of GABAergic function, such as by medications that block the degradation or reuptake of GABA. Examples of such a rational therapeutic approach include anticonvulsants that elevate brain GABA levels and are effective for the treatment of epilepsy and anxiety disorder.

Anxiety Disorders↗
PubMed2003

Persistent brain abnormalities in antiretroviral-naive HIV patients 3 months after HAART.

BACKGROUND: Proton magnetic resonance spectroscopy (1H-MRS) and neuropsychological tests may be useful for monitoring the effectiveness of highly active antiretroviral therapy (HAART) in HIV-associated brain injury. We aimed to evaluate whether brain abnormalities will improve 3 months after HAART. METHOD: Thirty-three HIV patients naive to antiretroviral medications were evaluated before and 3 months after HAART using 1H-MRS and neuropsychological tests; results were compared with those of 26 seronegative control subjects. RESULTS: Despite significant improvement in CD4 counts, and suppression of plasma and cerebrospinal fluid (CSF) viral loads, elevated brain metabolites (choline compounds and myoinositol in the frontal lobes) and neuropsychological tests abnormalities (including the computerized tests [CalCAP]) persisted after 3 months of HAART. In the basal ganglia, choline and myoinositol became elevated only after treatment. No interaction effect was observed between the number of CSF-penetrating drugs (one vs two) and changes (baseline vs 3 months) in any of the brain metabolites, cognitive performance or CSF viral load. CONCLUSIONS: The persistent brain abnormalities suggest ongoing repair or reactive inflammatory processes in the brain after 3 months of HAART. Regimens with two CSF-penetrating antiretroviral medications do not appear to be more effective than those with one CSF-penetrating drug in treating HIV brain injury at 3 months.

AIDS Dementia Complex↗
PubMed2002

Perfusion MRI and computerized cognitive test abnormalities in abstinent methamphetamine users.

This study aims to determine possible persistent abnormalities in regional cerebral blood flow (relative rCBF) and cognitive function in abstinent methamphetamine (METH) users. Twenty METH-dependent subjects (abstinent for 8+/-2 months) and 20 age- and gender-matched controls were evaluated with perfusion magnetic resonance imaging (pMRI) and neuropsychological tests. METH users showed decreased relative rCBF bilaterally in putamen/insular cortices (right: -12%; left: -10%) and the right lateral parietal brain region (-11%), but increased relative rCBF bilaterally in the left temporoparietal white matter (+13%), the left occipital brain region: (+10%) and the right posterior parietal region (+24%). Interaction effects were observed between METH and gender in the right occipital cortex and a midline brain region; female METH users showed increased relative rCBF (+15% both regions) whereas the male METH users had decreased relative rCBF (-10% and -18%, respectively). METH users performed within normal ranges on standard neuropsychological tests; however, they were slower on several tasks on the California Computerized Assessment Package (CalCAP), especially tasks that required working memory. These findings suggest that METH abuse is associated with persistent physiologic changes in the brain, and these changes are accompanied by slower reaction times on computerized measures of cognitive function.

Adult↗
PubMed2002

The effects of tamoxifen and estrogen on brain metabolism in elderly women.

BACKGROUND: Tamoxifen is used to treat breast cancer and may reduce the risk of breast cancer. However, there are conflicting reports as to whether tamoxifen use is associated with changes in brain metabolism and function or cognitive impairment. Consequently, we assessed the effects of tamoxifen and estrogen on the brain chemistry of elderly women. METHODS: We used proton magnetic resonance spectroscopy to measure the concentrations of N-acetyl-containing compounds, myo-inositol (MI), total creatine (creatine plus phosphocreatine), and choline-containing compounds in the frontal white matter, basal ganglia, and hippocampus of 76 elderly women of whom 16 had received tamoxifen therapy, 27 had received estrogen as hormone replacement therapy (HRT), and 33 had received neither (control group). A two-way analysis of variance (ANOVA) was performed to determine the statistical significance of differences in cerebral metabolite concentrations among subject groups and brain regions. All statistical tests were two-sided. RESULTS: Women in the tamoxifen and HRT groups had lower concentrations of MI in all areas than women in the control group (P =.02; overall group effect on ANOVA). Compared with the control group, the tamoxifen group (P =.004) and the HRT group (P =.06) had lower concentrations of MI in their basal ganglia. The MI concentration in the basal ganglia was inversely correlated with the duration of tamoxifen treatment (rho = -.72; P =.005). CONCLUSIONS: The reduced concentrations of MI in the brains of women treated with tamoxifen and HRT, compared with those of control women, suggest that tamoxifen has an effect similar to that of estrogen. These results, if confirmed, may alleviate concerns about the safety of using tamoxifen to reduce breast cancer risk in elderly women.

Aged↗
PubMed2002

Relationships among brain metabolites, cognitive function, and viral loads in antiretroviral-naïve HIV patients.

This study aims to determine the relationship among cerebral metabolite concentrations (on proton magnetic resonance spectroscopy or (1)H MRS), cognitive function, and clinical variables (CD4, plasma and CSF viral loads, and lipids) in antiretroviral medication-nai;ve HIV patients. We hypothesized that the probable glial markers myo-inositol [MI] and choline compounds [CHO] would correlate with cognitive function, CD4 count, and viral loads, but not with serum lipids. Forty-five antiretroviral-drug-nai;ve HIV patients and 25 control subjects were evaluated. Frontal lobe [MI], [CHO], and total creatine [CR] were elevated, while basal ganglia [CR] were decreased, with increasing dementia severity. As a group, HIV patients showed slowing on fine motor (Grooved Pegboard) and psychomotor function (Trails A & B), and deficits on executive function (Stroop tasks). Lower CD4 counts and elevated plasma viral loads were associated with elevated frontal white matter [MI], which in turn correlated with the Stroop tasks. These findings suggest that systemic factors (resulting from suppressed immune function and higher plasma viral load) may lead to glial proliferation (elevated [MI], [CHO], and [CR]) in the frontal white matter, which in turn may contribute to deficits on executive function in HIV. Studying antiretroviral-nai;ve patients minimized the confounding effects of antiretroviral treatment on the clinical, MRS, and neuropsychological variables, and allowed for a more accurate assessment of the relationships among these measurements. Metabolite concentrations, rather than metabolite ratios, should be measured since [CR], a commonly used reference for metabolite ratios, varies with disease severity in both frontal lobe and basal ganglia.

AIDS Dementia Complex↗
PubMed2002

Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue.

Information on over- and underexpressed genes in prostate cancer in comparison to adjacent normal tissue was sought by DNA microarray analysis. Approximately 12,600 mRNA sequences were analyzed from a total of 26 tissue samples (17 untreated prostate cancers, 9 normal adjacent to prostate cancer tissues) obtained by prostatectomy. Hierarchical clustering was performed. Expression levels of 63 genes were found significantly (at least 2.5-fold) increased, whereas expression of 153 genes was decreased (at least 2.5-fold) in prostate cancer versus adjacent normal tissue. In addition to previously described genes such as hepsin, overexpression of several genes was found that has not drawn attention before, such as the genes encoding the specific granule protein (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)-phospholipase A2, and the anti-apoptotic gene PYCR1. The radiosensitivity gene ATDC and the genes encoding the DNA-binding protein inhibitor ID1 and the phospholipase inhibitor uteroglobin were significantly down-regulated in the cancer samples. DNA microarray data for eight genes were confirmed quantitatively in five normal and five cancer tissues by real-time reverse transcriptase-polymerase chain reaction with a high correlation between the two methods. Laser capture microdissection of epithelial and stromal compartments from cancer and histological normal specimens followed by an amplification protocol for low levels of RNA (<0.1 microg) allowed us to distinguish between gene expression profiles characteristic of epithelial cells and those typical of stroma. Most of the genes identified in the nonmicrodissected tumor material as up-regulated were indeed overexpressed in cancerous epithelium rather than in the stromal compartment. We conclude that development of prostate cancer is associated with down-regulation as well as up-regulation of genes that show complex differential regulation in epithelia and stroma. Some of the gene expression alterations identified in this study may prove useful in the development of novel diagnostic and therapeutic strategies.

Adenocarcinoma↗