Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. METHODS: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. RESULTS: In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. CONCLUSIONS: This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.

Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis.

BACKGROUND AND PURPOSE: Brain atrophy is related to clinical deterioration in multiple sclerosis (MS) but its association with intrathecal markers of inflammation or neurodegeneration is unclear. Our aim was to investigate whether cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are associated with brain volume change in natalizumab-treated MS and whether this change is reflected in non-lesional white matter metabolites. METHODS: About 25 patients with natalizumab-treated MS were followed for 3 years with assessment of percentage brain volume change (PBVC) and absolute quantification of metabolites with proton magnetic resonance spectroscopy (1 H MRS). Analyses of inflammatory [interleukin 1ß (IL-1ß), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10, CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau proteins] markers were done at baseline and 1-year follow-up. RESULTS: The mean decline in PBVC was 3% at the 3-year follow-up, although mean 1 H MRS metabolite levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at baseline correlated negatively with PBVC over 3 years (r = -0.564, P = 0.012, and r = -0.592, P = 0.010, respectively). CONCLUSIONS: A significant 3-year whole-brain atrophy was not reflected in mean metabolite change of non-lesional white matter. In addition, our results suggest that CSF levels of NFL and tau correlate with brain atrophy development and may be used for evaluating treatment response in inflammatory active MS.

Feasibility of Catheter Placement Under Ultrasound Guidance for Progressive Preoperative Pneumoperitoneum for Large Incisional Hernia with Loss of Domain.

INTRODUCTION: Large incisional hernias with loss of domain (LIHLD) of the abdominal wall remain a therapeutic challenge due to the difficulty of replacing the contents of the hernia sac into the peritoneal cavity. Preoperative progressive pneumoperitoneum (PPP) is a valuable option. The purpose of this study was to evaluate the feasibility of peritoneal catheter insertion under ultrasound guidance for PPP and to compare the morbidity and mortality of this new technique to previously used techniques in our department. METHODS: Medical records were reviewed retrospectively from February 1989 to April 2013 in a single institution. Three different techniques of PPP were evaluated: surgical subcutaneous implantable port (SIP), surgical peritoneal dialysis catheter (PDC), and radiologic multipurpose drainage catheter (MDC). Collected data included patients' age, sex, body mass index, medical and surgical history, hernia location, PPP technique, length of hospitalization, volume of air injected, morbidity and mortality linked to PPP, and the procedure of hernia repair. RESULTS: Thirty-seven patients with a mean age of 63.1 years were evaluated. Progressive preoperative pneumoperitoneum was performed using SIP, PDC, and MDC for 14, 11, and 12 patients, respectively. Overall morbidity related to the technique was seen in 36 % of SIP, 27 % of PDC, and 0 % of MDC. One patient from the SIP group died on the 3rd postoperative day due to septic shock following aspiration pneumonia. No postoperative mortality in the other groups was observed. CONCLUSION: The MDC is an interesting modification of the original technique and is a safe procedure. It is a minimally invasive technique with a very low risk of perforation of the viscera. Therefore, the use of a non-absorbable prosthesis with MDC technique can be offered for all patients undergoing PPP without increasing the risk of infection.

Phosphorus-31: A table-top method for 3D B1-field amplitude and phase measurements.

A novel method of high-spatial-resolution, 3D B1-field distribution measurements is presented. The method is independent of the MR-scanner, and it allows for automated acquisitions of complete maps of all magnetic field vector components for both proton and heteronuclear MR coils of arbitrary geometrical shapes. The advantage of the method proposed here, compared with methods based on measurements with an MR-scanner, is that a complete image of both receive and transmit B1-fields, including the phase of the B1-field, can be acquired. The B1 field maps obtained in this manner can be used for absolute quantification of metabolites in MRS experiments, as well as for intensity compensations in imaging experiments, both of which are important concepts in biological and medical MR applications. Another use might be in coil development and testing. A comparison with B1 field magnitude maps obtained with an MR-scanner was included to validate the accuracy of the proposed method.

Procedure for quantitative (1)H magnetic resonance spectroscopy and tissue characterization of human brain tissue based on the use of quantitative magnetic resonance imaging.

PURPOSE: Existing methods for quantitative magnetic resonance spectroscopy are not widely used for magnetic resonance spectroscopy examinations in clinical practice due to the lengthy and difficult workflow. In this report, we aimed to investigate whether metabolite concentrations show co-variation with relaxation parameters (R1,H2O,R2,H2O), water concentration (CH2O), and age, using a quantitative magnetic resonance spectroscopy method, which is suitable for a clinical setting. METHODS: We performed 166 single voxel magnetic resonance spectroscopy measurements in the white matter and thalamus in 47 healthy subjects, aged 18-72 years. Whole brain R1,H2O, R2,H2O, and CH2O maps were determined for each subject using quantitative magnetic resonance imaging. Absolute metabolite concentrations were calculated by calibrating the water-scaled magnetic resonance spectroscopy, using the quantitative magnetic resonance imaging maps of R1,H2O, R2,H2O, and CH2O. RESULTS: Absolute concentrations in white matter of total Creatine and myo-Inositol were correlated with age (total Creatine: 12 ± 4 µM/year, P < 0.01; myo-Inositol: 23 ± 9 µM/year, P < 0.05), suggesting a process of increased glia density in aging white matter. Moreover, total Creatine and total N-acetylaspartate were inversely correlated with the R1,H2O and positively correlated with the CH2O of white matter. In addition, the Cramér-Rao lower bound was biased regarding the metabolite concentration, suggesting that should not be used as a quality assessment. CONCLUSION: The implemented method was fast, robust, and user-independent.

Brain Parcellation Repeatability and Reproducibility Using Conventional and Quantitative 3D MR Imaging.

BACKGROUND AND PURPOSE: Automatic brain parcellation is typically performed on dedicated MR imaging sequences, which require valuable examination time. In this study, a 3D MR imaging quantification sequence to retrieve R1 and R2 relaxation rates and proton density maps was used to synthesize a T1-weighted image stack for brain volume measurement, thereby combining image data for multiple purposes. The repeatability and reproducibility of using the conventional and synthetic input data were evaluated. MATERIALS AND METHODS: Twelve subjects with a mean age of 54 years were scanned twice at 1.5T and 3T with 3D-QALAS and a conventionally acquired T1-weighted sequence. Using SyMRI, we converted the R1, R2, and proton density maps into synthetic T1-weighted images. Both the conventional T1-weighted and the synthetic 3D-T1-weighted inversion recovery images were processed for brain parcellation by NeuroQuant. Bland-Altman statistics were used to correlate the volumes of 12 brain structures. The coefficient of variation was used to evaluate the repeatability. RESULTS: A high correlation with medians of 0.97 for 1.5T and 0.92 for 3T was found. A high repeatability was shown with a median coefficient of variation of 1.2% for both T1-weighted and synthetic 3D-T1-weighted inversion recovery at 1.5T, and 1.5% for T1-weighted imaging and 4.4% for synthetic 3D-T1-weighted inversion recovery at 3T. However, significant biases were observed between the methods and field strengths. CONCLUSIONS: It is possible to perform MR imaging quantification of R1, R2, and proton density maps to synthesize a 3D-T1-weighted image stack, which can be used for automatic brain parcellation. Synthetic parameter settings should be reinvestigated to reduce the observed bias.

Novel whole brain segmentation and volume estimation using quantitative MRI.

OBJECTIVES: Brain segmentation and volume estimation of grey matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) are important for many neurological applications. Volumetric changes are observed in multiple sclerosis (MS), Alzheimer's disease and dementia, and in normal aging. A novel method is presented to segment brain tissue based on quantitative magnetic resonance imaging (qMRI) of the longitudinal relaxation rate R(1), the transverse relaxation rate R(2) and the proton density, PD. METHODS: Previously reported qMRI values for WM, GM and CSF were used to define tissues and a Bloch simulation performed to investigate R(1), R(2) and PD for tissue mixtures in the presence of noise. Based on the simulations a lookup grid was constructed to relate tissue partial volume to the R(1)-R(2)-PD space. The method was validated in 10 healthy subjects. MRI data were acquired using six resolutions and three geometries. RESULTS: Repeatability for different resolutions was 3.2% for WM, 3.2% for GM, 1.0% for CSF and 2.2% for total brain volume. Repeatability for different geometries was 8.5% for WM, 9.4% for GM, 2.4% for CSF and 2.4% for total brain volume. CONCLUSION: We propose a new robust qMRI-based approach which we demonstrate in a patient with MS. KEY POINTS: • A method for segmenting the brain and estimating tissue volume is presented • This method measures white matter, grey matter, cerebrospinal fluid and remaining tissue • The method calculates tissue fractions in voxel, thus accounting for partial volume • Repeatability was 2.2% for total brain volume with imaging resolution <2.0 mm.

Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA: a pilot study.

OBJECTIVES: To develop and evaluate a procedure for quantifying the hepatocyte-specific uptake of Gd-BOPTA and Gd-EOB-DTPA using dynamic contrast-enhanced (DCE) MRI. METHODS: Ten healthy volunteers were prospectively recruited and 21 patients with suspected hepatobiliary disease were retrospectively evaluated. All subjects were examined with DCE-MRI using 0.025 mmol/kg of Gd-EOB-DTPA. The healthy volunteers underwent an additional examination using 0.05 mmol/kg of Gd-BOPTA. The signal intensities (SI) of liver and spleen parenchyma were obtained from unenhanced and enhanced acquisitions. Using pharmacokinetic models of the liver and spleen, and an SI rescaling procedure, a hepatic uptake rate, K (Hep), estimate was derived. The K (Hep) values for Gd-EOB-DTPA were then studied in relation to those for Gd-BOPTA and to a clinical classification of the patient's hepatobiliary dysfunction. RESULTS: K (Hep) estimated using Gd-EOB-DTPA showed a significant Pearson correlation with K (Hep) estimated using Gd-BOPTA (r = 0.64; P < 0.05) in healthy subjects. Patients with impaired hepatobiliary function had significantly lower K (Hep) than patients with normal hepatobiliary function (K (Hep) = 0.09 ± 0.05 min(-1) versus K (Hep) = 0.24 ± 0.10 min(-1); P < 0.01). CONCLUSIONS: A new procedure for quantifying the hepatocyte-specific uptake of T (1)-enhancing contrast agent was demonstrated and used to show that impaired hepatobiliary function severely influences the hepatic uptake of Gd-EOB-DTPA. KEY POINTS: • The liver uptake of contrast agents may be measured with standard clinical MRI. • Calculation of liver contrast agent uptake is improved by considering splenic uptake. • Liver function affects the uptake of the liver-specific contrast agent Gd-EOB-DTPA. • Hepatic uptake of two contrast agents (Gd-EOB-DTPA, Gd-BOPTA) is correlated in healthy individuals. • This method can be useful for determining liver function, e.g. before hepatic surgery.

Synthetic MRI of the brain in a clinical setting.

BACKGROUND: Conventional magnetic resonance imaging (MRI) has relatively long scan times for routine examinations, and the signal intensity of the images is related to the specific MR scanner settings. Due to scanner imperfections and automatic optimizations, it is impossible to compare images in terms of absolute image intensity. Synthetic MRI, a method to generate conventional images based on MR quantification, potentially both decreases examination time and enables quantitative measurements. PURPOSE: To evaluate synthetic MRI of the brain in a clinical setting by assessment of the contrast, the contrast-to-noise ratio (CNR), and the diagnostic quality compared with conventional MR images. MATERIAL AND METHODS: Twenty-two patients had synthetic imaging added to their clinical MR examination. In each patient, 12 regions of interest were placed in the brain images to measure contrast and CNR. Furthermore, general image quality, probable diagnosis, and lesion conspicuity were investigated. RESULTS: Synthetic T1-weighted turbo spin echo and T2-weighted turbo spin echo images had higher contrast but also a higher level of noise, resulting in a similar CNR compared with conventional images. Synthetic T2-weighted FLAIR images had lower contrast and a higher level of noise, which led to a lower CNR. Synthetic images were generally assessed to be of inferior image quality, but agreed with the clinical diagnosis to the same extent as the conventional images. Lesion conspicuity was higher in the synthetic T1-weighted images, which also had a better agreement with the clinical diagnoses than the conventional T1-weighted images. CONCLUSION: Synthetic MR can potentially shorten the MR examination time. Even though the image quality is perceived to be inferior, synthetic images agreed with the clinical diagnosis to the same extent as the conventional images in this study.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled 1H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification.

INTRODUCTION: Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). SUBJECTS AND METHODS: 16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. (1)H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. RESULTS: INPH patients had lower NAA (p=0.02) and lower tNA (p=0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myo-inositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. CONCLUSION: Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.

Environmental fluctuations and level of density-compensation strongly affects the probability of fixation and fixation times.

The probability of, and time to, fixation of a mutation in a population has traditionally been studied by the classic Wright-Fisher model where population size is constant. Recent theoretical expansions have covered fluctuating populations in various ways but have not incorporated models of how the environment fluctuates in combination with different levels of density-compensation affecting fecundity. We tested the hypothesis that the probability of, and time to, fixation of neutral, advantageous and deleterious mutations is dependent on how the environment fluctuates over time, and on the level of density-compensation. We found that fixation probabilities and times were dependent on the pattern of autocorrelation of carrying capacity over time and interacted with density-compensation. The pattern found was most pronounced at small population sizes. The patterns differed greatly depending on whether the mutation was neutral, advantageous, or disadvantageous. The results indicate that the degree of mismatch between carrying capacity and population size is a key factor, rather than population size per se, and that effective population sizes can be very low also when the census population size is far above the carrying capacity. This study highlights the need for explicit population dynamic models and models for environmental fluctuations for the understanding of the dynamics of genes in populations.

Right-hemispheric brain activation correlates to language performance.

Language function in the right-hemispheric homologues of Broca's and Wernicke's areas does not only correlate with left-handedness or pathology, but occurs naturally in right-handed healthy subjects as well. In the current study, two non-invasive methods of assessing language lateralization are correlated with behavioral results in order to link hemispheric dominance to language ability in healthy subjects. Functional magnetic resonance imaging (fMRI) together with a sentence-completion paradigm was used to determine region-specific lateralization indices in the left- and right-sided Broca's and Wernicke's areas, the frontal temporal lobe, the anterior cingulate cortex and the parietal lobe. In addition, dichotic listening results were used to determine overall language lateralization and to strengthen conclusions by correlating with fMRI indices. Results showed that fMRI lateralization in the superior parietal, the posterior temporal, and the anterior cingulate cortices correlated to dichotic listening. A decreased right ear advantage (REA), which indicates less left-hemispheric dominance in language, correlated with higher performance in most administered language tasks, including reading, language ability, fluency, and non-word discrimination. Furthermore, right hemispheric involvement in the posterior temporal lobe and the homologue of Broca's area suggests better performance in behavioral language tasks. This strongly indicates a supportive role of the right-hemispheric counterparts of Broca's and Wernicke's areas in language performance.

Children and television watching: a qualitative study of New Zealand parents' perceptions and views.

BACKGROUND: Television (TV) viewing is one of the most pervasive sedentary pursuits among children and adolescents. Research studies have shown that higher TV viewing hours are associated with a number of negative effects such as being overweight and obese, attention and behavioural problems, and impaired academic performance. Most interventions to reduce time spent watching TV have been school-based and little is known about the strategies that families use to control TV watching time. METHODS: Six focus groups with Maori, Pacific and non-Maori non-Pacific parents were conducted to examine New Zealand parents' perceptions of their children's TV watching. Focus groups explored attitudes towards TV viewing, strategies used to reduce viewing, and opinion on two different electronic monitors that can be used to restrict TV viewing. Focus group discussions were transcribed and a content analysis was conducted. RESULTS: Parents described TV as playing a dominant role in their family's lives, and highlighted several barriers to reducing children's TV viewing, such as parents not willing to reduce their own TV watching, a lack of safe alternatives to TV and the need to use TV as a babysitting tool. Limiting access to TV, making TV viewing a reward and finding alternative activities were current strategies parents employed to limit TV viewing; however, the barriers highlighted by parents make implementing such strategies difficult. Attitudes towards electronic monitor use to reduce TV viewing were mixed, but suggest further investigation of these devices is needed. CONCLUSIONS: Electronic devices that restrict the amount and content of TV viewing have some potential to support interventions and merit further investigation. It is imperative for interventions aimed at reducing TV viewing to consider the role TV plays within a family context, ensuring parental perceptions around the benefits and barriers of reducing TV are accounted for.

Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema.

Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R1), transverse relaxation (R2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R1-difference-map. The quantitative R1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.

Trophic and individual efficiencies of size-structured communities.

Individual and trophic efficiencies of size-structured communities are derived from mechanistically based principles at the individual level. The derivations are relevant for communities with a size-based trophic structure, i.e. where trophic level is strongly correlated with individual size as in many aquatic systems. The derivations are used to link Lindeman's trophic theory and trophic theory based on average individuals with explicit individual-level size spectrum theory. The trophic efficiency based on the transfer of mass between trophic levels through predator-prey interactions is demonstrated to be valid only when somatic growth can be ignored. Taking somatic growth into account yields an average individual growth efficiency that is smaller than the trophic efficiency.

Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects.

OBJECTIVE: To study the effect of fast-food-based hyper-alimentation on liver enzymes and hepatic triglyceride content (HTGC). DESIGN: Prospective interventional study with parallel control group. SETTING: University Hospital of Linköping, Sweden. PARTICIPANTS: 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group. INTERVENTION: Subjects in the intervention group aimed for a body weight increase of 5-15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks. MAIN OUTCOME MEASURES: Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention. RESULTS: Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p<0.001). Serum ALT increased from 22.1 (11.4) U/l at study start to an individual mean maximum level of 97 (103) U/l (range 19.4-447 U/l). Eleven of the 18 subjects persistently showed ALT above reference limits (women >19 U/l, men >30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls. CONCLUSION: Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whether recent excessive food intake has occurred.

Rapid magnetic resonance quantification on the brain: Optimization for clinical usage.

A method is presented for rapid simultaneous quantification of the longitudinal T(1) relaxation, the transverse T(2) relaxation, the proton density (PD), and the amplitude of the local radio frequency B(1) field. All four parameters are measured in one single scan by means of a multislice, multiecho, and multidelay acquisition. It is based on a previously reported method, which was substantially improved for routine clinical usage. The improvements comprise of the use of a multislice spin-echo technique, a background phase correction, and a spin system simulation to compensate for the slice-selective RF pulse profile effects. The aim of the optimization was to achieve the optimal result for the quantification of magnetic resonance parameters within a clinically acceptable time. One benchmark was high-resolution coverage of the brain within 5 min. In this scan time the measured intersubject standard deviation (SD) in a group of volunteers was 2% to 8%, depending on the tissue (voxel size = 0.8 x 0.8 x 5 mm). As an example, the method was applied to a patient with multiple sclerosis in whom the diseased tissue could clearly be distinguished from healthy reference values. Additionally it was shown that, using the approach of synthetic MRI, both accurate conventional contrast images as well as quantification maps can be generated based on the same scan.

IL-1beta and TNF-alpha regulate IL-6-type cytokines in gingival fibroblasts.

UNLABELLED: Interleukin-6 (IL-6)-type cytokines are pleiotropic molecules capable of stimulating bone resorption and expressed by numerous cell types. In the present study, we tested the hypothesis that gingival fibroblasts may exert local osteotropic effects through production of IL-6 and related cytokines. IL-6-type cytokine expression and regulation by IL-1beta and tumor necrosis factor-alpha (TNF-alpha) were studied in fibroblasts from the non-inflamed gingiva of healthy individuals. Constitutive mRNA expression of IL-6, IL-11, and leukemia inhibitory factor (LIF), but not of oncostatin M (OSM), was demonstrated, as was concentration-dependent stimulation of IL-6 and LIF mRNA and of protein by IL-1beta and TNF-alpha. IL-11 mRNA and protein were concentration-dependently stimulated by IL-1beta. The signaling pathway involved in IL-6 and LIF mRNA stimulation involved MAP kinases, but not NF-kappaB. The findings support the view that resident cells may influence the pathogenesis of periodontal disease through osteotropic IL-6-type cytokine production mediated by activation of MAP kinases. ABBREVIATIONS: IL-1alpha (interleukin-1alpha); IL-1beta (interleukin-1beta); IL-6 (interleukin-6); IL-11 (interleukin-11); LIF (leukemia inhibitory factor); OSM (oncostatin M); alpha(1)-coll. I (alpha(1)-collagen I); ALP (alkaline phosphatase); BMP-2 (bone morphogenetic protein-2); OC (osteocalcin); BSP (bone sialoprotein); TNFR I (tumor necrosis factor receptor I); TNFR II (tumor necrosis factor receptor II); IL-1R1 (interleukin-1 receptor 1); GAPDH (glyceraldehyde-3-phosphate dehydrogenase); RPL13A (ribosomal protein L13A); mRNA (messenger ribonucleic acid); cDNA (complementary deoxyribonucleic acid); PCR (polymerase chain-reaction); BCA (bicinchoninic acid); ELISA (enzyme-linked immunosorbent assay); alpha-MEM (alpha modification of Minimum Essential Medium); and FCS (fetal calf serum).

Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction.

BACKGROUND AND PURPOSE: The presence of edema will result in increased brain volume, which may obscure progressing brain atrophy. Similarly, treatment-induced edema reduction may appear as accelerated brain tissue loss (pseudoatrophy). The purpose of this study was to correlate brain tissue properties to brain volume, to investigate the possibilities for edema correction and the resulting improvement of the precision of automated brain volume measurements. MATERIALS AND METHODS: A group of 38 patients with clinically isolated syndrome or newly diagnosed MS were imaged at inclusion and after 1, 2, and 4 years using an MR quantification sequence. Brain volume, relaxation rates (R1 and R2), and proton density were measured by automated software. RESULTS: The reduction of normalized brain volume with time after inclusion was 0.273%/year. The mean SDs were 0.508%, 0.526%, 0.454%, and 0.687% at baseline and 1, 2, and 4 years. Linear regression of the relative change of normalized brain volume and the relative change of R1, R2, and proton density showed slopes of -0.198 (P < .001), 0.156 (P = .04), and 0.488 (P < .001), respectively. After we applied the measured proton density as a correction factor, the mean SDs decreased to 24.2%, 4.8%, 33.3%, and 17.4%, respectively. The observed atrophy rate reduced from 0.273%/year to 0.238%/year. CONCLUSIONS: Correlations between volume and R1, R2, and proton density were observed in the brain, suggesting that a change of brain tissue properties can affect brain volume. Correction using these parameters decreased the variation of brain volume measurements and may have reduced the effect of pseudoatrophy.