Conservative treatment of CMC-1 osteoarthritis

Initially, osteoarthritis of the carpometacarpal joint of the thumb (CMC-1) should be conservatively treated. However, literature concerning this topic is absent. Therefore, 39 patients (71 hands) with conservatively treated osteoarthritis of the carpometacarpal joint of the thumb were reviewed. The minimum follow-up period was I year; the average follow-up period was 8.8 years. Thirty-two women had bilateral CMC-I osteoarthritis; the remaining seven patients had unilateral CMC-1 osteoarthritis. Although suggested by others, long-term pain relief was not observed in this study. Moreover, patient satisfaction, thumb strength, and mobility were not influenced by the duration of the CMC-1 osteoarthritis. In conservatively treated patients, worse results are achieved than in operated patients, especially concerning their subjective experiences. The authors therefore advise surgery, especially in the case of pain which hampers the activities of daily life

Necrosis binding of Ac-Lys⁰(IRDye800CW)-Tyr³-octreotate: a consequence from cyanine-labeling of small molecules.

There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor uptake, especially when labeled to smaller targeting vectors such as peptides. Here we demonstrate the effect of cyanine-mediated dead cell-binding of Ac-Lys <sup>0</sup> (IRDye800CW)-Tyr <sup>3</sup> -octreotate (800CW-TATE) and how this can be used as an advantage for fluorescence-guided surgery. Binding of 800CW-TATE could be blocked with DOTA <sup>0</sup> -Tyr <sup>3</sup> -octreotate (DOTA-TATE) on cultured SSTR <sub>2</sub> -positive U2OS cells and was absent in SSTR <sub>2</sub> negative U2OS cells. However, strong binding was observed to dead cells, which could not be blocked with DOTA-TATE and was also present in dead SSTR <sub>2</sub> negative cells. No SSTR <sub>2</sub> -mediated binding was observed in frozen tumor sections, possibly due to disruption of the cells in the process of sectioning the tissue before exposure to the contrast agent. DOTA-TATE blocking resulted in an incomplete reduction of 61.5 ± 5.8% fluorescence uptake by NCI-H69-tumors in mice. Near-infrared imaging and dead cell staining on paraffin sections from resected tumors revealed that fluorescence uptake persisted in necrotic regions upon blocking with DOTA-TATE. This study shows that labeling peptides with cyanines can result in dead cell binding. This does not hamper the ultimate purpose of fluorescence-guided surgery, as necrotic tissue appears in most solid tumors. Hence, the necrosis binding can increase the overall tumor uptake. Moreover, necrotic tissue should be removed as much as possible: it cannot be salvaged, causes inflammation, and is tumorigenic. However, when performing binding experiments to cells with disrupted membrane integrity, which is routinely done with nuclear probes, this dead cell-binding can resemble non-specific binding. This study will benefit the development of fluorescent contrast agents

Brain tumour diagnostics using a DNA methylation-based classifier as a diagnostic support tool

Aims: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. Methods: About 502 CNS tumour samples were analysed using (850 k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. Results: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score >= 0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect, the MP result predicted the right diagnosis for three of these cases. In six cases, the suggested class was interpreted as 'discrepant but noncontributory'. The remaining 33.7% of cases (169/502) had a calibrated score Conclusions: MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information.</div

Anatomical alterations of the subthalamic nucleus in relation to age:A postmortem study

The subthalamic nucleus (STN) is currently the preferred target for chronic electrical high-frequency stimulation in Parkinson's disease. Anatomical determination of the exact position of the STN in the. individual patient, using magnetic resonance imaging, remains cumbersome, whereas calculation of the target using a stereotactic atlas bypasses patient interindividual variations in the exact delineation of the STN. The aim Of this Study was to demonstrate variations in shape and position of the STN during life. In this anatomopathological study, a method was applied to localize the STN in reference to the anterior commissure-posterior commissure line (AC-PC line) in 12 postmortem brains of patients who died of non-neurological diseases. Their age varied from 29 to 84 years. Centers and borders of the STN were macroscopically measured in three spatial orthogonal planes in relation to the AC-PC line, and verified by light microscopy. The AC-PC distance remains almost constant during life (24.4 mm; SD 3.58). With increasing age, the center of the STN tends to move 3.9 mm cranially, 2.6 mm laterally, and 0.2 mm anteriorly. This last result also differs from the position mentioned in the stereotactic brain atlases. The form of the STN also changes. During life, the STN becomes wider in the mediolateral direction and smaller in the superior-inferior and anterior-posterior direction. The shape and spatial position of the STN also change during life. These changes should be taken into account during target determination in deep brain stimulation procedures in Parkinson's disease. (c) 2005 Movement Disorder Society

Sensory nerve function and auto-mutilation after reconstruction of various gap lengths with nerve guides and autologous nerve grafts

The aim of this study was to evaluate sensory nerve recovery and auto-mutilation after reconstruction of various lengths of nerve gaps in the sciatic nerve of the rat, using different techniques. Group 4, in which the longest nerve gap (15 mm) was reconstructed with a thin-walled p(DL-lactide-y-caprolactone) nerve guide filled with modified denatured muscle tissue, showed the best results in the electro-stimulation tests and signs of severe auto-mutilation were not observed. Even in the control group, in which a 10mm nerve gap was left open, in two of the five rats improvement of the sensory nerve function was observed, which was caused by re-innervation of the sciatic nerve and not by expansion of the neighboring saphenous nerve. It is hypothesized that a better quality of nerve reconstruction/guidance channel/support results in faster regeneration and hence re-innervation, thereby, preventing auto-mutilation. A thin red glabrous skin, anhydrosis (dryness of the skin), short nails and edema were interpreted as signs of autonomic dysfunction. (C) 2001 Elsevier Science Ltd. All rights reserved