Comparison of Complete Distal Release of the Medial Collateral Ligament and Medial Epicondylar Osteotomy during Ligament Balancing in Varus Knee Total Knee Arthroplasty

Background

During ligament balancing for severe medial contracture in varus knee total knee arthroplasty (TKA), complete distal release of the medial collateral ligament (MCL) or a medial epicondylar osteotomy can be necessary if a large amount of correction is needed.

Methods

This study retrospectively reviewed 9 cases of complete distal release of the MCL and 11 cases of medial epicondylar osteotomy which were used to correct severe medial contracture. The mean follow-up periods were 46.5 months (range, 36 to 78 months) and 39.8 months (range, 32 to 65 months), respectively.

Results

There were no significant differences in the clinical results between the two groups. However, the valgus stress radiograph revealed significant differences in medial instability. In complete distal release of the MCL, some stability was obtained by repair and bracing but the medial instability could not be removed completely.

Conclusions

Medial epicondylar osteotomy for a varus deformity in TKA could provide constant medial stability and be a useful ligament balancing technique.     

Isolation of tumor spheres and mesenchymal stem-like cells from a single primitive neuroectodermal tumor specimen

Purpose

It has been reported that cancer stem cells (CSCs) can be isolated from primitive neuroectodermal tumor (PNET) specimens. Moreover, mesenchymal stem-like cells (MSLCs) have been isolated from Korean glioma specimens. Here, we tested whether tumor spheres and MSLCs can be simultaneously isolated from a single PNET specimen, a question that has not been addressed.

Methods

We isolated single-cell suspensions from PNET specimens, then cultured these cells using methods for MSLCs or CSCs. Cultured cells were analyzed for surface markers of CSCs using immunocytochemistry and for surface markers of bone marrow-derived mesenchymal stem cells (BM-MSCs) using fluorescence-activated cell sorting (FACS). Tumor spheres were exposed to neural differentiation conditions, and MSLCs were exposed to mesenchymal differentiation conditions. Possible locations of MSLCs within PNET specimens were determined by immunofluorescence analysis of tumor sections.

Results

Cells similar to tumor spheres and MSLCs were independently isolated from one of two PNET specimens. Spheroid cells, termed PNET spheres, were positive for CD133 and nestin, and negative for musashi and podoplanin. PNET spheres were capable of differentiation into immature neural cells and astrocytes, but not oligodendrocytes or mature neural cells. FACS analysis revealed that adherent cells isolated from the same PNET specimen, termed PNET-MSLCs, had surface markers similar to BM-MSCs. These cells were capable of mesenchymal differentiation. Immunofluorescence labeling indicated that some CD105⁺ cells might be closely related to endothelial cells and pericytes.

Conclusion

We showed that both tumor spheres and MSLCs can be isolated from the same PNET specimen. PNET-MSLCs occupied a niche in the vicinity of the vasculature and could be a source of stroma for PNETs.     

RIFLE classification in geriatric patients with acute kidney injury in the intensive care unit

Background

The RIFLE classification is widely used to assess the severity of acute kidney injury (AKI), but its application to geriatric AKI patients complicated by medical problems has not been reported.

Methods

We investigated 256 geriatric patients (≥65 years old; mean age, 74.4 ± 6.3 years) who developed AKI in the intensive care unit (ICU) according to the RIFLE classification. Etiologic, clinical, and prognostic variables were analyzed.

Results

They were categorized into RIFLE-R (n = 53), RIFLE-I (n = 102), and RIFLE-F (n = 101) groups. The overall in-hospital mortality was 39.8 %. There were no significant differences in RIFLE category between survivors and non-survivors. Survivors had significantly less needs for a ventilator and vasopressor, and lower number of failing organs. Survivors had higher systolic blood pressure, hemoglobin level, and serum albumin levels. We performed a logistic regression analysis to identify the independent predictors of in-hospital mortality. In a univariate analysis, hypertension, chronic kidney disease, RIFLE classification, number of failing organs, need for a ventilator and vasopressor, systolic blood pressure, hemoglobin level, and serum albumin levels were identified as prognostic factors of in-hospital mortality. However, in a multivariate analysis, hypertension, chronic kidney disease, number of failing organs, and serum albumin levels were independent risk factors, with no significant difference for in-hospital mortality with the RIFLE classification.

Conclusion

The RIFLE classification might not be associated with mortality in geriatric AKI patients in the ICU. In geriatric patients with AKI, various factors besides severity of AKI should be considered to predict mortality.

     

Involvement of Na+-Ca2+ exchanger on metabotropic glutamate receptor 1-mediated [Ca2+]i transients in rat cerebellar Purkinje neurons

Cerebellar Purkinje neurons have intracellular regulatory systems including Ca2+-binding proteins, intracellular Ca2+ stores, Ca2+-ATPase and Na+-Ca2+ exchanger (NCX) that keep intracellular Ca2+ concentration ([Ca2+]i) in physiological range. Among these, NCX interacts with AMPA receptors, activation of which induces cerebellar synaptic plasticity. And the activation of metabotropic glutamate receptor 1 (mGluR1) is also involved in the induction of cerebellar long-term depression. The interaction of NCX with mGluR1 is not known yet. Thus, in this study, the functional relationship between NCX and mGluR1 in modulating the [Ca2+]i in rat Purkinje neurons was investigated. The interaction between NCX and mGluR1 in Purkinje neurons was studied by measuring intracellular Ca2+ transients induced by an agonist of group I mGluRs, 3,5-dihydroxyphenylglycine (DHPG). The DHPG-induced Ca2+ transient was significantly reduced by treatments of NCX inhibitors, bepridil and KB-R7943. When cells were pretreated with antisense oligodeoxynucleotides of NCX, the DHPG-induced Ca2+ transient was also inhibited. These results suggest that NCX modulates the activity of mGluR1 in cerebellar Purkinje neurons. Therefore, NCX appears to play an important role in the physiological function of cerebellar Purkinje neurons such as synaptic plasticity.     

Activation of non-canonical NF-kappaB pathway mediated by STP-A11, an oncoprotein of Herpesvirus saimiri

Although Saimiri Transforming Protein (STP)-A11, an oncoprotein of Herpesvirus saimiri, has been known to activate NF-kappaB signaling pathway, the detailed mechanism has not been reported yet. We herein report that STP-A11 activates non-canonical NF-kappaB pathway, resulting in p100 processing to p52. In addition, translocation of p52 protein (NF-kappaB2) into the nucleus is observed by the expression of STP-A11. STP-A11-mediated processing of p100 to p52 protein requires proteosome-mediated proteolysis because MG132 treatment clearly blocked p52 production in spite of the expression of STP-A11. Analysis of STP-A11 mutants to activate NF-kappaB2 pathway discloses the requirement of TRAF6-binding site not Src-binding site for STP-A11-mediated NF-kappaB2 pathway. Blockage of STP-A11-mediated p52 production using siRNA against p52 enhanced a chemotherapeutic drug-mediated cell death, suggesting that p52 production induced by the expression of STP-A11 would contribute to cellular transformation, which results from a resistance to cell death.     

Comparative Efficacy and Bioequivalence of Novel H1-Antihistamine Bepotastine Salts (Nicotinate and Salicylate)

Bepotastine salts (nicotinate and salicylate) were investigated for their physicochemical properties to develop novel salt forms of bepotastine, bioequivalent to the bepotastine besilate-loaded tablet (Talion). These bepotastine salts of either nicotinate- or salicylate-loaded tablets were prepared by conventional wet granulation method, and dissolution profiles and pharmacokinetics in beagle dogs were compared to those of Talion. A novel bepotastine nicotinate has a higher solubility at varying pH levels (1.2, 4, or 6.8) than salicylate-loaded or besilate-loaded salt. In addition, those bepostastine salt forms (nicotinate and salicylate) are stable in heat, light, and water. Further, the novel nicotinate- and salicylate-loaded tablets showed similar dissolution rates to Talion in several selected dissolution media and were bioequivalent to Talion in beagle dogs in terms of area under the concentration–time curve (AUC) and maximum observed concentration (C_max). A pharmacokinetic study performed in beagle dogs demonstrated that test and reference products were found to be bioequivalent in terms of safety, efficacy, and pharmacokinetic properties. These results suggest that bepostastine nicotinate and salicylate formulations are considered applicable candidates and are well tolerated versus the conventional bepostastine besilate formulation.     

Impact of positive surgical margins and their locations after radical prostatectomy: comparison of biochemical recurrence according to risk stratification and surgical modality

Purpose

We investigated the influence of positive surgical margins (PSMs) and their locations on biochemical recurrence (BCR) according to risk stratification and surgical modality.

Methods

A total of 1,874 post-radical-prostatectomy (RP) patients of pT2–T3a between 2000 and 2010 at three tertiary centers, and who did not receive neoadjuvant/adjuvant therapy, were included in this study. Patients were stratified according to BCR risk: low risk (PSA <10, pT2a-b, and pGS ≤6), intermediate risk (PSA 10–20 and/or pT2c and/or pGS 7), and high risk (PSA >20 or pT3a or pGS 8–10). The median follow-up was 43 months.

Results

PSMs were a significant predictor of BCR in both the intermediate- and high-risk-disease groups (P = .001, HR 2.1, 95 % CI 1.3–3.4; P < .001, HR 2.8, 95 % CI 2.0–4.1). Positive apical margin was a significant risk factor for BCR in high-risk disease (P = .003, HR 2.0, 95 % CI 1.2–3.3), but not in intermediate-risk disease (P = .06, HR 1.7, 95 % CI 0.9–3.1). Positive bladder neck margin was a significant risk factor for BCR in both intermediate- and high-risk disease (P < .001, HR 5.4, 95 % CI 2.1–13.8; P = .001, HR 4.5, 95 % CI 1.8–11.4). In subgroup analyses, robotic RP provided comparable BCR-free survival regardless of risk stratification. Patients with PSMs showed similar BCR-free survival between open and robotic RP (log-rank, P = .897).

Conclusions

Post-RP PSMs were a significantly independent predictor of disease progression in high-risk disease as well as intermediate-risk disease. Both positive apical and bladder neck margins are also significant risk factors of BCR in high-risk disease. Patients with PSMs showed similar BCR-free survival between open and robotic surgery.