Optical coherence tomography-based assessment of retinal vascular pathology in cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a disorder of brain vasculature that causes various structural changes in the brain parenchyma, and is associated with various clinical symptoms such as cognitive impairment and gait disorders. Structural changes of brain arterioles cannot be visualized with routine imaging techniques in vivo. However, optical coherence tomography (OCT) is thought to be a "window to the brain". Thus, retinal vessel parameters may correlate with CSVD characteristic brain lesions and cerebrospinal fluid biomarkers (CSF) of the neuropathological processes in CSVD like endothelial damage, microglial activation and neuroaxonal damage. METHODS: We applied OCT-based assessment of retinal vessels, magnetic resonance imaging (MRI), and CSF biomarker analysis in a monocentric prospective cohort of 24 patients with sporadic CSVD related stroke and cognitive impairment. MRI lesions were defined according to the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). Biomarkers were assessed using commercially available ELISA kits. Owing to the unavailability of an age-matched control-group lacking MRI-characteristics of CSVD, we compared the retinal vessel parameters in CSVD patients (73.8 ± 8.5 years) with a younger group of healthy controls (51.0 ± 16.0 years) by using an age- and sex-adjusted multiple linear regression analysis model. RESULTS: Among the parameters measured with OCT, the Wall to Lumen Ratio (WLR) but not Mean Wall Thickness (MWT) of the superior branch of the retinal artery correlated significantly with the volume of white matter hyperintensities on MRI (rs = - 0.5) and with CSF-levels of Chitinase 3 like 1 protein (rs = - 0.6), zona occludens 1 protein (rs = - 0.5) and GFAP (rs = - 0.4). MWT and WLR were higher in CSVD than in controls (28.9 µm vs. 23.9 µm, p = 0.001 and 0.32 vs. 0.25, p = 0.001). CONCLUSIONS: In this exploratory study, WLR correlated with the volume of white matter hyperintensities, and markers of vascular integrity, microglial activation, and neuroaxonal damage in CSVD. Further prospective studies should clarify whether retinal vessel parameters and CSF biomarkers may serve to monitor the natural course and treatment effects in clinical studies on CSVD.

The neuroanatomy of subthreshold depressive symptoms in Huntington's disease: a combined diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) study.

BACKGROUND: Depressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being. METHOD: We compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). RESULTS: Frequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions. CONCLUSIONS: Current subthreshold depressive symptoms in early HD are associated with microstructural changes - without concomitant brain volume loss - in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology.

Tumor necrosis factor alpha inhibitors as immunomodulatory antirejection agents after intestinal transplantation.

We reported the successful administration of infliximab for late-onset OKT3-resistant rejection in two patients, who presented persistent ulcerative inflammation of the ileal graft after intestinal transplantation (ITX). Based on this experience, the present study demonstrated our long-term experience with infliximab for different types of rejection-related and inflammatory allograft alterations. Infliximab administration (5 mg/kg body weight (BW)) was initiated at a mean of 18.2 ± 14.1 months after transplantation. The number of administrations per patient averaged 8.4 ± 6.7. Repeat dosing was timed according to clinical signs and graft histology in addition to serum-levels of tumor necrosis factor alpha (TNFα), lipopolysaccharide binding protein (LBP) and C-reactive protein (CRP). Infliximab was successful in the following patients: patients with late-onset OKT3- and steroid-refractory rejection who presented persistent ulcerative alterations of the ileal graft (n = 5), patients with ulcerative ileitis/anastomositis, who did not show typical histological rejection signs (n = 2), and one patient with early-onset OKT3-resistant rejection. Infliximab was not successful in one patient with early-onset OKT3-resistant rejection that was accompanied by treatment-refractory humoral rejection. In conclusion, infliximab can expand therapeutic options for late-onset OKT3- and steroid-refractory rejection and chronic inflammatory graft alterations in intestinal allograft recipients.

Quantitative muscle ultrasound in neuromuscular disorders using the parameters 'intensity', 'entropy', and 'fractal dimension'.

BACKGROUND AND PURPOSE: Ultrasound is a useful non-invasive instrument in visualizing physiological and pathological morphology in skeletal muscle. Here, we evaluate the possibility that quantitative muscle ultrasound using the parameters 'intensity', 'entropy', and 'fractal dimension' is a feasible method to distinguish between dystrophic myopathies (DM), inflammatory myopathies (IM), and motor neuron disorders. METHODS: Seven patients with IM, 12 patients with DM, nine patients with motor neuron diseases, and 24 healthy subjects underwent an identical ultrasound examination protocol, applied on gastrocnemius and tibialis anterior muscle. Analysis parameters were applied on grey scale images as well as on gradient images. RESULTS: Statistical evaluation revealed no significant differences in the evaluated parameters for differentiation of the distinct disease groups. Compared with healthy controls however we found statistically significant differences between almost of all the investigated parameters, even in disease cases with clinically unaffected distal musculature. CONCLUSION: The parameters are able to distinguish between healthy and affected musculature but not between distinct disease entities. Studies are needed to establish whether or not the parameters are helpful to monitor muscle involvement and disease progression in neuromuscular diseases.

The contribution of white and gray matter differences to developmental dyslexia: insights from DTI and VBM at 3.0 T.

Developmental dyslexia is one of the most common neuropsychological disorders in children and adults. Only few data are available on the pathomechanisms of this specific dysfunction, assuming--among others--that dyslexia might be a disconnection syndrome of anterior and posterior brain regions involved in phonological and orthographic aspects of the reading process, as well as in the integration of phonemes and graphemes. Therefore, diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) were used to verify the hypothesis of altered white and gray matter structure in German dyslexic adults. DTI revealed decreased fractional anisotropy (FA) in bilateral fronto-temporal and left temporo-parietal white matter regions (inferior and superior longitudinal fasciculus). Significant correlations between white matter anisotropy and speed of pseudoword reading were found. In dyslexics, gray matter volumes (as measured by VBM) were reduced in the superior temporal gyrus of both hemispheres. So far, our results, based on a combined analysis of white and gray matter abnormalities, provide exceedingly strong evidence for a disconnection syndrome or dysfunction of cortical areas relevant for reading and spelling. Thus, we suggest that this imbalance of neuronal communication between the respective brain areas might be the crucial point for the development of dyslexia.

[Systematic diagnosis of erythrocytosis]. / Systematische diagnostiek van erytrocytose.

Erythrocytosis is a phenomenon with life-threatening complications and a broad differential diagnosis. Erythrocytosis is usually secondary to a cardiopulmonary condition leading to a low arterial oxygen tension. A probable diagnosis can often be made on the basis of the history, physical examination, a measurement of the peripheral oxygen saturation, and simple laboratory tests. The differential diagnosis can be narrowed down by a determination of the erythropoietin concentration and the JAK2 mutation. If the erythrocytosis is found to be non-physiological, then reduction of the haematocrit via bloodletting and, depending on the diagnosis, treatment with acetylsalicylic acid are indicated.

A combination of alleles 2 of interleukin (IL)-1A(-889) and IL-1B(+3954) is associated with lower gingival bleeding tendency in plaque-induced gingivitis in young adults of Arabic heritage.

The aim of this study was to investigate the possible association of a distinct combination of polymorphisms in the interleukin (IL)-1 gene cluster on gingival bleeding tendency in young adult Arabs with plaque-induced gingivitis. Fifty otherwise healthy, nonsmoking volunteers, 19-28 years of age, participated. Clinical examinations included periodontal probing depth, bleeding on probing, and plaque index. Probing was done with a pressure-controlled probe at about 1.27 MPa. Examinations were repeated after 2 and 4 weeks. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. A subject carrying alleles 2 at IL-1A ( -889 ) and IL-1B ( +3954 ) was designated genotype-positive. Twenty-six subjects were genotype-positive (52%). A repeated measures two-level (occasion, subject) model of the proportion of sites bleeding on probing, which was adjusted for gender, average plaque index, probing depth, and calculus, revealed a significantly lower proportion of bleeding sites in genotype-positive subjects (estimate -0.050, standard error 0.025, p < 0.05). Biserial correlations of bleeding proportions were high (0.71-0.78), confirming the steady-state plaque environment. It was concluded that inflammatory responses to dental plaque were considerably dampened in genotype-positive, nonsmoking young adults of Arabic heritage.

Preservation of diffusion tensor properties during spatial normalization by use of tensor imaging and fibre tracking on a normal brain database.

White matter connectivity in the human brain can be mapped by diffusion tensor magnetic resonance imaging (DTI). After reconstruction, the diffusion tensors, the diffusion amplitude and the diffusion direction can be displayed on a morphological background. Consequently, diffusion tensor fibre tracking can be applied as a non-invasive in vivo technique for the delineation and quantification of specific white matter pathways. The aim of this study was to show that normalization to the Montreal Neurological Institute (MNI) stereotaxic standard space preserves specific diffusion features. Therefore, techniques for tensor imaging and fibre tracking were applied to the normalized brains as well as to the group averaged brain data. A normalization step of individual data was included by registration to a scanner- and sequence-specific DTI template data set which was created from a normal database transformed to MNI space. The algorithms were tested and validated for a group of 13 healthy controls.

Effect of triclosan/copolymer-containing toothpaste on the association between plaque and gingival bleeding: a randomized controlled clinical trial.

AIM: To study longitudinal associations between plaque and gingival bleeding and multilevel variance/covariance structures after introducing triclosan-containing toothpaste. MATERIAL AND METHODS: A 10-week, randomized, two-arm, double-masked, controlled clinical trial was conducted in 34 healthy, non-smoking females with plaque-induced gingivitis. Clinical periodontal examinations were repeated every other week. At week 4, test toothpaste containing 0.24% sodium monofluorophosphate, 0.3% triclosan, and 2% polyvinyl-methyl ether maleic acid; or control toothpaste containing 0.76% sodium monofluorophosphate and 0.1% sodium fluoride, were randomly distributed. RESULTS: Multivariate multilevel models indicated that, after introducing experimental toothpastes, subject random error was reduced from 0.6 to below 0.2. The odds ratio (OR) of bleeding on probing (BOP) was about 30% less in the test than in the control group (p<0.01). At the end of the experiment, ORs for BOP and plaque index scores 1-3 (reference 0) were 2.1-2.4 in the control group, but 1.1-1.9 in the test group (p<0.05). No effects on plaque levels and calculus were observed. CONCLUSIONS: Multivariate multilevel modelling allows the study of fixed and random effects of experimental toothpastes on gingival inflammation in small sample. Triclosan appears to attenuate the causal association between supragingival plaque and gingival bleeding in gingivitis.

Multivariate multilevel models for repeated measures in the study of smoking effects on the association between plaque and gingival bleeding.

Multivariate multilevel modeling was applied to analyze repeated measures data on the influence of heavy smoking on the association between the amount of supragingival plaque and gingival bleeding on probing (BOP) in a steady-state plaque environment. Data acquired in 65 systemically healthy young adults with mild plaque-induced gingivitis were analyzed. 33 heavy smokers consumed at least 20 cigarettes per day while 32 were non-smokers. Periodontal examinations at the outset consisted of periodontal probing depth, clinical attachment level, BOP, plaque index, and presence of calculus at 6 sites of every tooth present. They were repeated 3 times every 8 weeks. A multivariate 4-level variance component model revealed that the odds of BOP was twice as high in smokers. In addition, females had a lower likelihood for BOP but, with increasing bleeding scores during the course of the study, this effect attenuated. Low biserial correlations for BOP at the site level of between 0.11 and 0.2 were found. At the tooth level, correlations were moderate (0.2-0.5), and highest at the subject level (0.8-0.9). Variations at subject and tooth levels were very large at the outset but notably attenuated in the course of the study. Plaque consistently influenced the tendency for BOP with an odds ratio of about 1.7-1.8 for each increase in score in both smokers and non-smokers. The present study did not reveal evidence for attenuation of the plaque/gingival bleeding relationship in heavy smokers.

Noise reduction in magnetocardiography by singular value decomposition and independent component analysis.

In the routine recording of magnetocardiograms (MCGs), it is necessary to underline the problem of noise cancellation. Source separation has often been suggested to solve this problem. In this paper, blind source separation (BSS), by means of singular value decomposition (SVD) and independent component analysis (ICA), was used for noise reduction in MCG data to improve the signal to noise ratio. Special techniques, based on statistical parameters, for identifying noise and disturbances, have been introduced to automatically eliminate noise-related and disturbance-related components before reconstructing cleaned data sets. The results show that ICA and SVD can detect and remove a variety of noise and artefact sources from MCG data, as well as from stress MCG.

Using independent component analysis for noise reduction of magnetocardiographic data in case of exercise with an ergometer.

In 1992, Brockmeier et al. showed that there is a strong difference in magnetocardiography (MCG)-detected field distribution generated by the heart at rest and under stress. To study the possible clinical applications of this finding, it is convenient to avoid pharmacological stress and to perform stress MCG (SMCG) using conventional physical stress with an ergometer. When using a non-magnetic ergometer, the MCG recordings under physical stress are more noisy due to the unavoidable movement artefacts from the patient and from the residual artefacts of the ergometer. To remove these artefacts a denoising was performed using independent component analysis (ICA) in a new implementation. This work shows that with ICA in this special implementation it is becoming feasible to extract heart signals from SMCG data recorded during ergometer exercise.

Prevalence and clinical significance of an elevated cardiac troponin I in patients presenting to the Emergency Department without chest pain.

BACKGROUND: Cardiac troponins are currently measured in patients presenting with chest pain. Little is known about routinely measured cardiac troponins in patients presenting without chest pain. The aim of this study was to determine the prevalence and clinical significance of an elevated cardiac troponin I (cTnI) in patients presenting to the Emergency Department without chest pain. METHODS: During a 6-month period, we routinely measured cTnI in all patients presenting to the internist, neurologist, or lung specialist for reasons other than chest pain. We followed patients with an elevated cTnI for 1 year and determined mortality and incidence of non-fatal myocardial infarction, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). RESULTS: cTnI was elevated in 41 out of 1130 patients (3.6%). Patients with an elevated cTnI were older (78 vs. 62 years) and more often admitted to the hospital (95% vs. 78%) than those with a normal cTnI. Twenty-six patients (63%) with an elevated cTnI died within 1 year. Approximately 50% of these deaths were cardiac-related. Two patients (4.9%) suffered a non-fatal myocardial infarction, while no patient underwent PCI or CABG during follow-up. CONCLUSION: Routinely measured cTnI is seldom elevated in a general population of patients presenting to the Emergency Department without chest pain. Patients with an elevated cTnI are, on the average, 16 years older than those with a normal level. An elevated cTnI is clearly associated with an unfavorable outcome.

Gingival bleeding on repeat probing after different time intervals in plaque-induced gingivitis.

The aim of this study was to assess agreement and association of gingival bleeding after repeated probing at different time intervals in subjects with gingivitis. Twenty adults participated. Periodontal probing (P approximately 1.27 MPa) was conducted at six sites of every tooth present. Probing was repeated in different quadrants immediately after the first probing (T0), after 1 h (T1), 4 h (T4), and 24 h (T24). A total of 3,459 sites were probed twice. The mean proportion of sites bleeding on probing (BOP) was 0.23 (standard deviation 0.08, range 0.10-0.41). Probing itself had a significant effect on the results of repeated probing. For T0 through T24, respective mean differences of proportions were 0.04, 0.04, 0.01, and -0.03. Ninety-five percent repeatability coefficients of proportions were 0.17-0.18. Estimates of overall kappa were 0.390, 0.234, 0.233, and 0.046 for T0 through T4, respectively. Adjusted two-level binary response models revealed odds ratios (95% confidence interval) for BOP at T0 through T4 of 6.52 (4.34, 9.80), 3.23 (2.19, 4.76), 3.80 (2.63, 5.50), and 2.68 (1.85, 3.89). It was concluded that a certain degree of agreement of site-specific bleeding scores in subjects with plaque-induced gingivitis could be observed only if probing was repeated at once. Adjusted associations between repeat BOP were weak in general, but strongest immediately after first probing. There appears to be a significant effect of probing itself, which may last for more than 1 h, whereas 24-h results are obtained under different conditions.

Open magnetic and electric graphic analysis.

The OMEGA software provides an analysis platform for user-independent, fast, and reproducible multimodal data analysis in one single software environment. Synergetic interactions pursued between the two functional imaging techniques fMRI and MEG use the morphological MRI recording as a basis for a common coordinate frame. In this way, direct interchange, comparison, and integration among the results of the different modalities have become feasible. The fMRI data analysis provides information about the localization of functional activity with low temporal resolution, whereas the MEG recording complements the corresponding time evolution with a high temporal resolution. The implementation of OMEGA allows the analyst to receive comprehensive MEG/fMRI results in a matter of minutes after the measurements have been completed. With OMEGA, the clinical researcher gets comprehensive information in a quick and standardized approach about the sites and the time course of neurological activation, which is useful for clinical applications and diagnostics.

A novel approach for the averaging of magnetocardiographically recorded heart beats.

Performing signal averaging in an efficient and correct way is indispensable since it is a prerequisite for a broad variety of magnetocardiographic (MCG) analysis methods. One of the most common procedures for performing the signal averaging to increase the signal-to-noise ratio (SNR) in magnetocardiography, as well as in electrocardiography (ECG), is done by means of spatial or temporal techniques. In this paper, an improvement of the temporal averaging method is presented. In order to obtain an accurate signal detection, temporal alignment methods and objective classification criteria are developed. The processing technique based on hierarchical clustering is introduced to take into account the non-stationarity of the noise and, to some extent, the biological variability of the signals reaching the optimum SNR. The method implemented is especially designed to run fast and does not require any interaction from the operator. The averaging procedure described in this work is applied to the averaging of MCG data as an example, but with its intrinsic properties it can also be applied to the averaging of ECG recording, averaging of body-surface-potential mapping (BSPM) and averaging of magnetoencephalographic (MEG) or electroencephalographic (EEG) signals.

Variance components of gingival thickness.

OBJECTIVES: Distinct periodontal phenotypes have been identified by cluster analysis, which is an explorative method with very low external validity. The aim of the present study was to investigate variance components of facial gingival thickness in young adults with mild gingivitis. MATERIAL AND METHODS: Thirty-three non-smoking females, 18-23 years of age, with mild or moderate plaque-induced gingivitis participated. Gingival thickness was measured at every tooth present by use of ultrasound technology to the next 0.1 mm with a lowest measurement of 0.5 mm. Periodontal probing depth and clinical attachment level were measured with a pressure-controlled probe. Gingival bleeding index was assessed after probing on a 0-2 scale, where 1 was slight, and 2 was profuse bleeding on probing. The Silness-Loe plaque index was recorded. Multilevel variance components and random intercept models were built. RESULTS: A 2-level (subject, tooth) variance component model of gingival thickness without any explanatory variable revealed an intercept (mean) of 0.93 +/- 0.02 mm. Subject variation of gingival thickness amounted to 4.2% of the total variance. Addition of tooth- and subject-related covariates to the model revealed, after adjusting for tooth type, an association with periodontal probing depth (estimated coefficient 0.067 +/- 0.025), and considerable association with average bleeding index (-0.395 +/- 0.149) and plaque index (0.125 +/- 0.048). Variation at the tooth level was drastically reduced; subject variation amounted to 5.2%. CONCLUSION: Gingival thickness is mainly associated with tooth-related variables. Bleeding tendency is higher if gingiva is thin. Subject variability related to periodontal phenotype may add to the total variance, however, to a very low extent.

A new strategy for easy volume conductor modelling in magnetocardiography.

Modelling the electromagnetic properties of the thorax in magnetocardiographic (MCG) studies is usually performed by the Boundary Element Method (BEM). Magnetic Resonance Imaging (MRI) scans are generally used as the basis for extracting the coordinates for BEM. As MRI is a (time) expensive technique and scanners have a high use demand, in this work a strategy is presented that reduces the costs and the need for additional MRI images. This strategy is based on the use of low resolution and incomplete MRI image sets of the thorax.