Increased sensory feedback in Tourette syndrome

Tourette syndrome (TS) is a neuro-psychiatric disorder being characterized by motor and phonic tics typically preceded by sensory urges. Given the latter the role of the sensory system and sensorimotor interaction in TS has recently gained increased attention. 12 TS patients and 12 matched control subjects performed two tasks, requiring simple finger movements: a Go/NoGo task and a self paced movement task. Neurophysiological data was recorded using magnetoencephalography (MEG). Event related responses around movement onset, i.e. motor field (MF) occurring directly prior to the movement and movement evoked field (MEF) immediately after movement onset were analyzed using dipole modeling. MF peak amplitudes did not differ between groups in either task. In contrast, in both tasks MEF peak amplitudes were increased in TS patients. Moreover, larger MEF amplitudes during self paced movements were inversely correlated with motor tic frequency and severity. Enlarged MEF amplitudes as a marker of early sensory feedback of one's own movements probably represent enlarged sensory input from the periphery resulting from altered subcortical gating. We conclude that TS patients exhibit altered sensory-motor processing involved in voluntary movement control, which might also be successful in tic control.     

Expression of microRNA 210 associates with poor survival and age of tumor onset of soft-tissue sarcoma patients

Expression of microRNAs can affect age of tumor onset and prognosis of cancer patients. However, nothing is known about the effects of microRNAs on altered age of cancer onset and disease-specific survival of soft-tissue sarcoma (STS) patients. The levels of miR-210, also known as hypoxia-regulated microRNA, were analyzed by quantitative real-time (RT)-PCR in the tumors of 78 STS patients. The patients were stratified according to their microRNA levels with low, intermediate and high expression levels and the association of microRNA expression and patients' survival was analyzed using multivariate Cox's regression hazard analyses. A significant correlation between an intermediate miR-210 expression and disease-specific death of STS patients [relative risk (RR) = 3.19; p = 0.018] was observed compared with patients with high expression levels in their tumors. Interestingly, the association between an intermediate expression of miR-210 and a poor prognosis was only significant in female STS patients (RR = 11.28; p = 0.010), but not observed in male individuals. Furthermore, the expression of miR-210 showed a significant association with the age of tumor onset in a gender-specific manner. Specifically, male patients with an intermediate expression of miR-210 associated with a 9.6-year later age of tumor onset (p = 0.017) compared with males with a low expression of miR-210 in their tumors. However, no significant differences in the female patients were observed. This study provides the first evidence of a correlation of expression levels of a single microRNA (miR-210) with the prognosis and age of tumor onset in a gender-specific manner in STS patients.     

Neuropilin‐2 and its ligand VEGF‐C predict treatment response after transurethral resection and radiochemotherapy in bladder cancer patients

The standard treatment for invasive bladder cancer is radical cystectomy. In selected patients, bladder‐sparing therapy can be performed by transurethral resection (TURBT) and radio‐chemotherapy (RCT) or radiotherapy (RT). Our published in vitro data suggest that the Neuropilin‐2 (NRP2)/VEGF‐C axis plays a role in therapy resistance. Therefore, we studied the prognostic impact of NRP2 and VEGF‐C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n = 198) or RT (n = 49) and a follow‐up time up to 15 years. A tissue microarray was analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor in overall survival (OS; HR: 3.42; 95% CI: 1.48 – 7.86; p = 0.004) and was associated with a 3.85‐fold increased risk of an early cancer specific death (95% CI: 0.91 – 16.24; p = 0.066) in multivariate analyses. Cancer specific survival (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p = 0.037). Patients with high VEGF‐C expression have a 2.29‐fold increased risk of shorter CSS (95% CI: 1.03–5.35; p = 0.043) in univariate analysis. CSS dropped from 170 months to 88 months in the case of high VEGF‐C expression (p = 0.041). Additionally, NRP2 and VEGF‐C coexpression is a prognostic marker for OS in multivariate models (HR: 7.54; 95% CI: 1.57–36.23; p = 0.012). Stratification for muscle invasiveness (T1 vs. T2‐T4) confirmed the prognostic role of NRP2 and NRP2/VEGF‐C co‐expression in patients with T2‐T4 but also with high risk T1 disease. In conclusion, immunohistochemistry for NRP2 and VEGF‐C has been determined to predict therapy outcome in bladder cancer patients prior to TURBT and RCT.     

Role of two single nucleotide polymorphisms in secreted frizzled related protein 1 and bladder cancer risk

In this study, we determined the genotype distribution of two single nucleotide polymorphisms (SNPs) in secreted frizzled related protein 1 (SFRP1), rs3242 and rs921142, in a Caucasian bladder cancer case-control study. Allelic variants of the SNPs were determined using restriction fragment length polymorphism (RFLP) analysis and partly verified by sequencing analysis. Overall, DNA from 188 consecutive and 215 early-onset bladder cancer patients (≤45 years) as well as from 332 controls was investigated. Potential microRNA binding sites were determined for rs3242, and microRNA expression was analysed in cell lines and tumour specimens. We observed a remarkable distribution difference in rs3242 between bladder cancer patients and healthy controls (p=0.05). Additionally, we found a significant difference in genotype distribution (p=0.032), resulting from the difference of early-onset patients and the control group (p=0.007). The risk allele T showed increased frequency in the early-onset patient group (p=0.002). Genotype-dependent differences of microRNA binding capacity were predicted in SFRP1 mRNA for two microRNAs. Hsa-miR-3646 showed strong expression in cell lines and tumour tissue, whereas hsa-miR-603 exhibited weak expression. The rs921142 SNP showed no significant association with bladder cancer risk. This is the first study to describe an association of the SFRP1 SNP rs3242 and bladder cancer risk as well as the influence of rs3242 on genotype-dependent microRNA capacity on SFRP1 mRNA. The onset of bladder seems to be associated with the increased occurrence of the T-allele in rs3242.     

Intravascular malignant lymphoma (angiotrophic large-cell lymphoma)

Intravascular lymphoma (IVL) is characterized by proliferation of large malignant lymphoid cells within the lumen of small vessels. Sites usually affected include the central nervous system and skin although involvement of multiple organ symptoms have been described. IVL is very rare and aggressive type of lymphoma. Based on review of the literature we present clinicopathological, immunohistochemical and molecular features of the IVL. The etiological possibilities are discussed.     

In vivo evaluation of nerve guidance channels of PTMC/PLLA porous biomaterial

Introduction

Peripheral nerve disruptions, frequently occurring during limb injuries, give rise to serious complications of patients recovery resulting from limitations in neural tissue regeneration capabilities. To overcome this problem bridging techniques utilizing guidance channels gain their importance. Biodegradable polymeric tubes seem to be more prospective then non-degradable materials – no necessity of implant removal and possibilities of release of incorporated drugs or biologically active agents that may support nerve regeneration process are the main advantages.

Material and methods

Polymer blend of commercial poly(L-lactic acid) (PLLA) and in-house synthesized poly(trimethylene carbonate) (PTMC) were processed in an organic solvent – phase inversion process on a supporting rod – to form a guidance porous tube of 1.1 mm inner diameter. In vivo experiments on rat''s cut femoral nerve by using either the tubes or end-to-end suturing (control group) involved 22 and 19 rats, respectively. Motor recovery of operated limbs, neuroma occurrence and histopathology of explanted nerves were evaluated after 30, 60 and 90 days of implantation.

Results

Motor recovery of the limbs was of similar rate for the two animal groups. The neuroma formation was evident in over 90% control specimens, while for the bridging group it was less than 40% of all evaluable samples (p = 0.0022). Biocompatibility of applied materials was affirmed by moderate tissue response.

Conclusions

Application of the biodegradable PLLA/PTMC polymeric tubes effectively supports regeneration of discontinued nerves. The applied material prevents neuroma formation, by reducing the scar tissue formation time and, thus, accelerating the process of neural tissue restoration.     

Utility of immunohistochemistry markers in the interpretation of post-high-intensive focussed ultrasound prostate biopsy cores

Purpose

To overcome the difficulties in the interpretation of postoperative tumor obtaining biopsy cores for patients who treated their prostate cancer with high-intensity focussed ultrasound (HIFU) therapy.

Methods

The H&E slides of 58 patients with residual prostate cancer after HIFU treatment were systematically reviewed. Correlation between the pathologist’s findings and immunohistochemical expression of MIB-1, alpha-Methyl-Co-Racemase and 34βE-12 staining was analyzed.

Results

Mean time from treatment to biopsy was 40.2 (8–208) weeks. The expert review of the H&E slides identified 40 patients with viable carcinoma in the post-HIFU biopsy cores. 18 patients were revised to necrosis-only-tumors. These biopsies were performed not later than 16 weeks after HIFU treatment (median 10.9 weeks, range 8–14). Both MIB-1 and AMACR staining displayed significant differential expression in viable carcinoma (p < 0.001) compared to necrosis tumors. Referring to viable carcinoma tissue, AMACR staining index was significantly rising, the longer treatment dated back from biopsy (p < 0.002). In this context, 34-β-E12 stained negative through all tumor areas and positive in the majority (85%) of the surrounding non-neoplastic epithelium.

Conclusions

AMACR and MIB-1 reliably differentiate viable carcinoma from a process of ongoing irreversible necrosis in early post-HIFU prostate biopsy cores and therefore proposed—in addition with 34 beta-E12—as useful markers exposing suspicious tumor foci in difficult cases.     

Nuclear E-cadherin Expression is Associated with the Loss of Membranous E-cadherin, Plasmacytoid Differentiation and Reduced Overall Survival in Urothelial Carcinoma of the Bladder

Background

Loss of E-cadherin represents a hallmark of plasmacytoid differentiation. We analyzed the effect of membranous E-cadherin loss and its nuclear accumulation in patients with locally advanced conventional urothelial carcinoma (UC) who were treated with radical cystectomy and adjuvant chemotherapy.

Methods

A total of 247 formalin-fixed, paraffin-embedded tumor samples were reviewed to detect histological variants of UC. Immunohistochemical staining of E-cadherin was performed and analyzed for membranous and nuclear expression. The correlation between E-cadherin expression and histology was assessed, and overall survival (OS) was analyzed with univariate and multivariate Cox regression and Kaplan–Meier analyses. Correlation of nuclear E-cadherin to tumor stage (pT), lymph node metastasis (pN), histologic subtype, and chemotherapy was performed by Fisher’s exact test.

Results

Membranous and nuclear E-cadherin expression was strongly correlated to plasmacytoid urothelial carcinoma (PUC) (p < 0.001). Complete loss of membranous E-cadherin expression was observed in 76.2 % of PUCs, 11.1 % of conventional UCs, and 0 % of micropapillary urothelial carcinoma (MPCs). Nuclear accumulation was found in 47.6 % of PUCs, 10 % of MPCs, and 1.8 % of UCs. Sixty-two percent of all tumors with negative membranous E-cadherin expression and nuclear accumulation were PUCs (p = 0.035). In a Kaplan–Meier analysis, mean survival with nuclear E-cadherin expression was 31.9 months [95 % confidence interval (CI) 16.1–47.6] of patients without nuclear staining 61 months (95 % CI 53.5–67.7; p = 0.045). A univariate Cox regression analysis showed that nuclear E-cadherin accumulation was associated with a 2-fold increase in risk of death (95 % CI 1.03–4.06; p = 0.04). In multivariate Cox regression analysis adjusted to type of chemotherapy, tumor stage, and tumor grade, the hazard ratio for patients with nuclear E-cadherin was 2.03 (95 % CI 1.00–4.121; p = 0.050).

Conclusions

Nuclear E-cadherin is associated with PUCs and is suggested to be an independent prognostic factor in advanced UC.     

Are recent available blended collagen-calcium phosphate better than collagen alone or crystalline calcium phosphate? Radiotextural analysis of a 1-year clinical trial

Clinical Oral Investigations - The purpose of this study is to compare bone regeneration properties of recently available collagen-calcium phosphate (C-CP) blend as bone substitute (BS) material in...