Assessment of glycosaminoglycan concentration changes in the intervertebral disc via chemical exchange saturation transfer

In this study, it is shown that the chemical exchange saturation transfer (CEST) method for hydroxyl protons can be used to detect changes in glycosaminoglycan (GAG) concentration in the intervertebral disc. The method, termed gagCEST, was demonstrated ex vivo by correlating the CEST effect with the fixed charge density (FCD) of the nucleus pulposus (NP), as well as by correlating tissue CEST images with their corresponding ²³Na images. Incubation of five NP samples with trypsin produced samples with varying GAG content (n = 19). A good correlation was found between the –OH CEST effect and FCD, as well as with the N‐acetyl signal amplitude. gagCEST images in vitro further illustrated the amount of detail obtainable from this contrast mechanism when compared with conventional imaging. The large concentration of GAG and the relatively long T₁ of water in NP make the method sensitive, in particular, for the assessment of GAG depletion in this tissue. It is the loss of GAG in NP that indicates the early stage of disc degeneration. Copyright © 2011 John Wiley & Sons, Ltd.     

GHSR DNA hypermethylation is a common epigenetic alteration of high diagnostic value in a broad spectrum of cancers

Identification of a single molecular trait that is determinant of common malignancies may serve as a powerful diagnostic supplement to cancer type-specific markers. Here, we report a DNA methylation mark that is characteristic of seven studied malignancies, namely cancers of lung, breast, prostate, pancreas, colorectum, glioblastoma and B cell chronic lymphocytic leukaemia (CLL) (n = 137). This mark was defined by substantial hypermethylation at the promoter and first exon of growth hormone secretagouge receptor (GHSR) through bisulfite pyrosequencing. The degree of aberrant methylation was capable of accurate discrimination between cancer and control samples. The highest sensitivity and specificity of cancer detection was achieved for cancers of pancreas, lung, breast and CLL yielding the area under the curve (AUC) values of 1.0000, 0.9952, 0.9800 and 0.9400, respectively. Narrowing to a single CpG site within the gene''s promoter or four consecutive CpG units of the highest methylation levels within the first exon improved the detection power. GHSR hypermethylation was detected already at the early stage tumors. The accurate performance of this marker was further replicated in an independent set of pancreatic cancer and control samples (n = 78). These findings support the candidature of GHSR methylation as a highly accurate pan-cancer marker.     

Supramalleolar osteotomies for degenerative joint disease of the ankle joint: indication, technique and results

Patients with varus or valgus hindfoot deformities usually present with asymmetric ankle osteoarthritis. In-vitro biomechanical studies have shown that varus or valgus hindfoot deformity may lead to altered load distribution in the tibiotalar joint which may result in medial (varus) or lateral (valgus) tibiotalar joint degeneration in the short or medium term. The treatment of asymmetric ankle osteoarthritis remains challenging, because more than half of the tibiotalar joint surface is usually preserved. Therefore, joint-sacrificing procedures like total ankle replacement or ankle arthrodesis may not be the most appropriate treatment options. The short- and midterm results following realignment surgery, are very promising with substantial pain relief and functional improvement observed post-operatively. In this review article we describe the indications, surgical techniques, and results from of realignment surgery of the ankle joint in the current literature.     

Subtalar instability: diagnosis and treatment

Subtalar instability is challenging to diagnose. It rarely follows a complete subtalar dislocation, an event more likely to result in subtalar pain, stiffness, and arthritis. By history, subtalar instability can be suggested by the patient’s feeling of ankle instability, easy “rolling over,” and a need to look at the ground constantly when walking. Clinical measures for inversion and eversion do not accurately reflect isolated subtalar motion, as soft tissue and other joint motion confound the examination. Stress radiographs have high false positive rates. Magnetic resonance imaging can show injured or disorganized ligaments suggestive of recurrent subtalar strain, but are not dynamic studies and cannot alone diagnose instability. Operative treatment, when elected, should focus on determining the source of the problem. Generally direct repair of the lateral ligaments is sufficient. Bony malalignment should always be considered especially in the setting when previous ligament reconstruction has failed.     

Beitrag zur pathologischen Anatomie und zu den Leitungsbahnen des Rautenhirns bei den Kleinhirnbrückenwinkeltumoren

Ohne ZusammenfassungDem klinischen Krankenhause der 1. Moskauer Staatsuniversität zum 150. Jubiläum gewidmet.     

Dependence of NMR noise line shapes on tuning,matching, and transmission line properties

The tuning and matching conditions of rf circuits, as well as the properties of the transmission lines connecting these to the preamplifier, have direct consequences for NMR probe sensitivity and as for the optimum delivery of rf power to the sample. In addition, tuning/matching conditions influence radiation damping effects, which manifest themselves as fast signal flip‐back and line broadening effects, and can lead to concentration‐dependent frequency shifts. Previous studies have also shown that the appearance of spin‐noise and absorbed circuit noise signals heavily depended on tuning settings. Consequently, all these phenomena are linked together. The mutual connections and interdependences of these effects are highlighted and reviewed here. © 2014 The Authors Concepts in Magnetic Resonance, Part B: Magnetic Resonance Engineering Published by Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 44B: 1–11, 2014     

Ex vivo assessment of mouse cervical remodeling through pregnancy via 23Na MRS

Preterm birth occurs in 12.5% of births in the United States and can lead to risk of infant death or to lifelong serious health complications. A greater understanding by which the two main processes, uterine contraction and cervical remodeling are regulated is required to reduce rates of preterm birth. The cervix must undergo extensive remodeling through pregnancy in preparation for parturition, the process of labor and delivery of young. One key aspect of this dynamic process is a change in the composition and abundance of glycosaminoglycans (GAGs) and proteoglycans within the extracellular matrix, which influences the loss of tensile strength or stiffness of the cervix during labor. 23Na NMR spectroscopy has previously been validated as a method to quantify GAGs in tissues. In the current study, the Na+ concentration was measured at several time points through pregnancy in mouse cervices using 23Na NMR spectroscopy. The Na+ concentration increased progressively during pregnancy and peaked one day before birth followed by a rapid decline after birth. The same trend was seen in GAGs as measured by a biochemical assay using independent cervix samples over the course of pregnancy. We suggest that monitoring the Na+ concentration via 23Na NMR spectroscopy can serve as an informative physiological marker in evaluating the stages of cervical remodeling ex vivo and warrants further investigation to determine its utility as a diagnostic tool for the identification of women at risk for impending preterm birth.