A protocol for manual segmentation of medial temporal lobe subregions in 7 Tesla MRI.

Recent advances in MRI and increasing knowledge on the characterization and anatomical variability of medial temporal lobe (MTL) anatomy have paved the way for more specific subdivisions of the MTL in humans. In addition, recent studies suggest that early changes in many neurodegenerative and neuropsychiatric diseases are better detected in smaller subregions of the MTL rather than with whole structure analyses. Here, we developed a new protocol using 7 Tesla (T) MRI incorporating novel anatomical findings for the manual segmentation of entorhinal cortex (ErC), perirhinal cortex (PrC; divided into area 35 and 36), parahippocampal cortex (PhC), and hippocampus; which includes the subfields subiculum (Sub), CA1, CA2, as well as CA3 and dentate gyrus (DG) which are separated by the endfolial pathway covering most of the long axis of the hippocampus. We provide detailed instructions alongside slice-by-slice segmentations to ease learning for the untrained but also more experienced raters. Twenty-two subjects were scanned (19-32 yrs, mean age = 26 years, 12 females) with a turbo spin echo (TSE) T2-weighted MRI sequence with high-resolution oblique coronal slices oriented orthogonal to the long axis of the hippocampus (in-plane resolution 0.44 × 0.44 mm2) and 1.0 mm slice thickness. The scans were manually delineated by two experienced raters, to assess intra- and inter-rater reliability. The Dice Similarity Index (DSI) was above 0.78 for all regions and the Intraclass Correlation Coefficients (ICC) were between 0.76 to 0.99 both for intra- and inter-rater reliability. In conclusion, this study presents a fine-grained and comprehensive segmentation protocol for MTL structures at 7 T MRI that closely follows recent knowledge from anatomical studies. More specific subdivisions (e.g. area 35 and 36 in PrC, and the separation of DG and CA3) may pave the way for more precise delineations thereby enabling the detection of early volumetric changes in dementia and neuropsychiatric diseases.

Comparison of In Vivo and Ex Vivo MRI of the Human Hippocampal Formation in the Same Subjects.

Multiple techniques for quantification of hippocampal subfields from in vivo MRI have been proposed. Linking in vivo MRI to the underlying histology can help validate and improve these techniques. High-resolution ex vivo MRI can provide an intermediate modality to map information between these very different imaging modalities. This article evaluates the ability to match information between in vivo and ex vivo MRI in the same subjects. We perform rigid and deformable registration on 10 pairs of in vivo (3 T, 0.4 × 0.4 × 2.6 mm3) and ex vivo (9.4 T, 0.2 × 0.2 × 0.2 mm3) scans, and describe differences in MRI appearance between these modalities qualitatively and quantitatively. The feasibility of using this dataset to validate in vivo segmentation is evaluated by applying an automatic hippocampal subfield segmentation technique (ASHS) to in vivo scans and comparing SRLM (stratum/radiatum/lacunosum/moleculare) surface to manual tracing on corresponding ex vivo scans (and in 2 cases, histology). Regional increases in thickness are detected in ex vivo scans adjacent to the ventricles and were not related to scanner, resolution differences, or susceptibility artefacts. Satisfactory in vivo/ex vivo registration and subvoxel accuracy of ASHS segmentation of hippocampal SRLM demonstrate the feasibility of using this dataset for validation, and potentially, improvement of in vivo segmentation methods.

Assessment of the Hemostatic Parameters and Platelet Function on Thromboelastometry and Impedance Aggregometry in Hemodialysis Patients Qualified for Kidney Transplantation: Preliminary Report.

BACKGROUND: Chronic kidney disease is one of the medical conditions that affect hemostasis. Patients undergoing hemodialysis present both hemorrhagic and prothrombotic tendencies. Platelet adhesion to the artificial surface of the dialyzer's membrane, blood vessel endothelial wall disruption, and quantitative and qualitative changes in clothing factors are thought to be causative agents of the above-mentioned conditions. Thromboelastometry and impedance aggregometry enable precise assessment of clot formation and platelet function abnormalities, including changes related to chronic renal failure in patients undergoing renal replacement therapy. METHODS: A prospective study with control group was designed. The study group consisted of 17 adults with diagnosed chronic renal failure undergoing hemodialysis. The control group consisted of 13 healthy volunteers. EXTEM and FIBTEM tests in rotational thromboelastometry and TRAPtest in impedance aggregometry analyzer were performed. RESULTS: EXTEM parameter test results were comparable between analyzed groups, whereas FIBTEM test results were significantly increased in the study group. Platelet aggregation as measured by the TRAPtests was significantly decreased in patients undergoing hemodialysis. CONCLUSIONS: In end-stage renal disease patients undergoing hemodialysis, whole-blood clot formation is not disturbed, even though platelet dysfunction occurs. Increased fibrin clot formation reflected by FIBTEM results may compensate the observed platelet disorders. The compilation of ROTEM and Multiplate may support appropriate hemostatic control and decision-making during kidney transplantation.

Automated Hippocampal Subfield Segmentation at 7T MRI.

BACKGROUND AND PURPOSE: High resolution 7T MRI is increasingly used to investigate hippocampal subfields in vivo, but most studies rely on manual segmentation which is labor intensive. We aimed to evaluate an automated technique to segment hippocampal subfields and the entorhinal cortex at 7T MRI. MATERIALS AND METHODS: The cornu ammonis (CA)1, CA2, CA3, dentate gyrus, subiculum, and entorhinal cortex were manually segmented, covering most of the long axis of the hippocampus on 0.70-mm(3) T2-weighted 7T images of 26 participants (59 ± 9 years, 46% men). The automated segmentation of hippocampal subfields approach was applied and evaluated by using leave-one-out cross-validation. RESULTS: Comparison of automated segmentations with corresponding manual segmentations yielded a Dice similarity coefficient of >0.75 for CA1, the dentate gyrus, subiculum, and entorhinal cortex and >0.54 for CA2 and CA3. Intraclass correlation coefficients were >0.74 for CA1, the dentate gyrus, and subiculum; and >0.43 for CA2, CA3, and the entorhinal cortex. Restricting the comparison of the entorhinal cortex segmentation to a smaller range along the anteroposterior axis improved both intraclass correlation coefficients (left: 0.71; right: 0.82) and Dice similarity coefficients (left: 0.78; right: 0.77). The accuracy of the automated segmentation versus a manual rater was lower, though only slightly for most subfields, than the intrarater reliability of an expert manual rater, but it was similar to or slightly higher than the accuracy of an expert-versus-manual rater with ∼170 hours of training for almost all subfields. CONCLUSIONS: This work demonstrates the feasibility of using a computational technique to automatically label hippocampal subfields and the entorhinal cortex at 7T MRI, with a high accuracy for most subfields that is competitive with the labor-intensive manual segmentation. The software and atlas are publicly available: http://www.nitrc.org/projects/ashs/.

The effects of in vitro hemodilution and fibrinogen concentrate substitution on thromboelastometry analysis in patients qualified for liver transplantation - preliminary results.

BACKGROUND: Dilutional coagulopathy might cause life-threatening hemorrhages in liver transplantation. Liver insufficiency is usually accompanied by alteration in fibrinogen (Fib) synthesis, which is one of the main clotting factors providing appropriate hemostasis. Intraoperative hemodilution results in further Fib concentration reduction enhancing coagulopathy and blood loss. Exogenous Fib substitution might prevent this. METHODS: A prospective study with a control group was designed. The study group consists of patients with cirrhosis who qualified for liver transplantation. Inclusion and exclusion criteria were strictly established. The blood collected from participants was diluted up to 30% and 60% with crystalloid (saline) or colloid (hydroxyethyl starch) in 2 parallel series. The first series consisted of diluted blood, the second of diluted blood with Fib concentrate. Thromboelastometry tests were performed on every blood sample. After collecting data from the first 12 participants, we performed a preliminary analysis. RESULTS: The maximum clot formation (MCF) in the EXTEM test decreased with progressive blood dilution in both study arms. The MCF values were lower than 35 mm in every diluted blood sample of the study group. The recovery of decreased MCF after Fib concentrate substitution was observed in both groups. The improvement in clot formation was also expressed as amplitude of clot firmness in the 10th minute (A10) in the FIBTEM test. CONCLUSIONS: Clot formation is disturbed more profoundly by hemodilution in cirrhotic patients. Fib concentrate substitution might be effective in the management of dilutional coagulopathy.

Physicochemical and dissolution studies of simvastatin solid dispersions with Pluronic F127.

Simvastatin (SIM) solid dispersions with Pluronic F127 (PLU) obtained by kneading and fusion methods were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier Transform Infrared Spectroscopy (FTIR). DSC studies demonstrate that the SIM/PLU solid dispersions formed a simple eutectic phase diagram. FTIR spectroscopy and XRPD studies of obtained mixtures showed no interaction between the components in the solid state and confirmed the absence of terminal solid solutions. Intrinsic dissolution studies of solid dispersions in 0.5% sodium lauryl sulfate solution (SLS) indicated that the dissolution rate markedly increased in these solid dispersions systems compared with pure SIM. The increase in dissolution rate strongly depended on ratios of drug to carriers and selection of the method of preparations of mixtures. The solid dispersions prepared in the weight ratios of 60.0/40.0% and 69.9/30.1% w/w of SIM/PLU by the kneading method showed the highest improvement in wettability and dissolution rate of SIM. Approximately 100% of the drug was dissolved from these mixtures in comparison to 3.84% of pure simvastatin within 120 min.

[Retinal damage by (hydroxy)chloroquine intake: published evidence for an efficient ophthalmological follow-up]. / Netzhautschädigung bei (Hydroxy-)Chloroquin-Einnahme: Evidenzlage als Basis für eine rationale augenärztliche Untersuchungsstrategie.

BACKGROUND: Irreversible maculopathy and retinopathy are well-known adverse effects of chloroquine and hydroxychloroquine. For this article the literature was screened for relevant risk factors. The results were used for recommendations concerning the extent and frequency of ophthalmological monitoring. METHODS: A systematic literature review was undertaken. RESULTS: Very few studies on a high evidence level could be retrieved for this problem. Most of the risk factors have not been addressed sufficiently. A higher dosage per kg body mass, long therapy duration, presence of keratopathy and renal or hepatic dysfunction are probably associated with an increased risk to develop a maculopathy/retinopathy. Additional factors such as age, genetic disposition, additional retinal disease, sunlight exposition and nature plus duration of the underlying disease have not sufficiently been demonstrated. Gender, body mass and even the accumulated dosage do not contribute as risk factors according to current knowledge. CONCLUSION: Beside patient risk factors, the spectrum of ophthalmological methodology and cost considerations have to be considered when thinking about content and frequency of monitoring for the risk of acquiring a (hydroxy)chloroquine-induced maculopathy or retinopathy. In principle, a baseline examination comprising visual acuity (near and far), 10 degree threshold perimetry, colour vision, slit lamp (cornea) and funduscopy is reasonable. One of the high investment techniques such as multifocal ERG, fundus autofluorescence and high resolution optical coherence tomography should be used depending on the existing equipment and experience but not more often than once a year. In suspicious cases or high risk-patients a flexible approach is mandatory.

Insulin availability from mucoadhesive tablets.

The widespread implementation of peptides as drugs encounters numerous obstacles, the main being invasive and inconvenient parenteral administration. Oral transmucosal administration is one of the possible alternatives, valuable for its noninvasiveness and easy accessibility. The aim of our study was to determine the implementation possibilities of mucoadhesive tablets prepared on a methylcellulose and sodium alginate basis with an addition of absorption-modifying hyaluronic acid, as carriers for peptides destined for oral transmucosal administration. Two series of 50 mg tablets containing 5mg of insulin were prepared for the study. The first series contained methylcellulose, hyaluronic acid and mannitol, while the second series' formulation included sodium alginate, hyaluronic acid and mannitol. Carried out study confirmed that insulin administration in the form of mucoadhesive tablets lowers blood glucose levels in rabbits. Better effects were reached in vivo in the case of MC-based tablets, for which stronger and longer glycemia lowering was achieved.

Synthesis and antibacterial activity of 1,3-diarylpyrimido[4,5-d]pyrimidines.

This paper describes the synthesis of 4,5-diaminoderivatives of pyrimidine and pyrimido [4,5-d] pyrimidines and evaluation of their antibacterial activity on 9 selected bacterial species relatif the changes in the chemical structure to an increase in the bioactive properties.

The application of polyvinyl alcohol in the technology of modern drug form.

The following presentation is a review of literature related to application of nonionic polymer, polyvinyl alcohol, in the technology of modern drug form. The review contains the description of physical-chemical properties of this polymer, such as hydrolysis degree, solubility, swelling capacity. Each characteristic is followed by the description of its application as a therapeutical substance carrier in the pharmacy.

Resorbed polymeric sponge used as a carrier the therapeutic substance. Part 1. Gelatine sponge.

The obtaining of porous, elastic gel matrix, as a carrier of therapeutic substance, with long decomposition time was the aim of the research. The gelatin extracted from pig skin (Fisher Chemicals Schweiz) and 86% glycerol (Chempur) was used in experiments. The studies showed that such biopolymer as gelatine enable to prepare the matrix which can remain in an organism for a time long enough and a porous structure of the sponge allows to increase absorbing capacity of exudate.

The influence of selected bioadhesive polymers on physical-chemical properties of stomatological dressing.

Dressings made from polyvinyl alcohol (PAV) and Hydroxypropylmethylcellulose (HPMC) with the addition of glycerol (GLY) differ in adhesiveness and the time of wash out in water, both characteristics depended on polymer and GLY concentration. The research on the release speed which is applied in topical therapy of chlorhexidine digluconate antiseptic in biopharmaceutical model proved the existence of close to rectilinear relation between the amount of released substance and release time for selected formulations.

Two-kaon correlations in central Pb+Pb collisions at 158 a GeV/c.

Two-particle interferometry of positive kaons is studied in Pb+Pb collisions at mean transverse momenta approximately 0.25 and 0.91 GeV/c. A three-dimensional analysis was applied to the lower p(T) data, while a two-dimensional analysis was used for the higher p(T) data. We find that the source-size parameters are consistent with the m(T) scaling curve observed in pion-correlation measurements in the same collisions, and that the duration time of kaon emission is consistent with zero within the experimental sensitivity.

Study of interaction of gastrointestinal agents in the presence of cytoprotective drugs. Part II. In vitro study on the adsorption of selected spasmolytic drugs on sucralfate.

The subject of the research was the adsorption of selected musculotropic and cholinolytic spasmolytics on a cytoprotective drug--sucralfate. Adsorption evaluation was made by a static method, in vitro, the environment reaction, the concentrations of the tested drugs and the sucralfate form being taken into account. The obtained results prove that the analysed therapeutic substances are adsorbed on the sucralfate in all pH. The highest bonding capacity was observed in tests at pH=3.6, in the presence of sucralfate, which at this pH occurs in the form of suspension. The lowest capacity was at pH=1.5 in the presence of sucralfate in the paste form. In the group of the tested drugs, scopolamine butylbromide is adsorbed best, drotaverine hydrochloride little less and papaverine hydrochloride least of all.

Resorbable polymeric sponges as drug carriers. Part 2. Gelatin sponge.

The aim of the research is to obtain a porous and bioresorbable gelatin matrix, which could be used as a drug carrier. The research presented in the paper is a continuation of the work carried out earlier.

Study of interaction of gastroenterological agents in the presence of cytoprotective drugs. Part I: Adsorption of the chosen inhibitors of histamine H2 receptors on sucralfat in vitro.

We investigated adsorption of the chosen histamine H2 receptor inhibitors on sucralfat. Evaluation of adsorption was conducted by statistic methods in vitro taking into account environment reaction and sucralfat form. The obtained results prove that the tested therapeutic substances are adsorbed on sucralfat in all used pH ranges and the ability of sucralfat bounding depends on its form and environment reaction. The highest adsorption value was observed in the samples with pH 3.6 in the presence of sucralfat suspension, and the lowest in environment pH 1.5 in the presence of sucralfat paste. From among the tested histamine receptors ranitidine hydrochloride is adsorbed in the best way and cimetidine hydrochloride and famotidine in much worse way.

Synthesis and biological properties of 4-hydroxy, 4-thio-5-pyrimidine derivatives.

4-Oxy as well as 4-thio-5-carboxy and 5-hydroxy pyrimidine derivatives were synthesized and their microbiological properties were compared.

Synthesis and biological investigations of pyrimidine derivatives.

The study concerns new syntheses of 5-hydroxy ether and 5-aminohydroxy ether derivatives of pyrimidine. When tested for antibacterial activity, some of the compounds exhibited promising effects.