Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death

Adenosine triphosphate (ATP) is known to induce cell death in T lymphocytes at high extracellular concentrations. CD4+ and CD8+ T lymphocytes have a differential response to ATP, which in mice is due to differences in the P2X7 receptor expression levels. By contrast, we observed that the difference in human CD4+ and CD8+ T lymphocyte response toward the synthetic ATP-analog BzATP is not explained by a difference in human P2X7 receptor expression. Rather, the BzATP-induced human P2X7 receptor response in naïve and immune-activated lymphocyte subtypes correlated with the expression of another ATP-binding receptor: the human P2Y11 receptor. In a recombinant expression system, the coexpression of the human P2Y11 receptor counteracted BzATP-induced human P2X7 receptor-driven lactate dehydrogenase release (a marker of cell death) and pore formation independent of calcium signaling. A mutated non-signaling human P2Y11 receptor had a similar human P2X7 receptor-inhibitory effect on pore formation, thus demonstrating that the human P2X7 receptor interference was not caused by human P2Y11 receptor signaling. In conclusion, we demonstrate an important species difference in the ATP-mediated cell death between mice and human cells and show that in human T lymphocytes, the expression of the human P2Y11 receptor correlates with human P2X7 receptor-driven cell death following BzATP stimulation

Ceramic on ceramic bearing fractures in total hip arthroplasty : an analysis of data from the national joint registry

Aims: Ceramic-on-ceramic (CoC) bearings in total hip arthroplasty (THA) are commonly used but concerns exist regarding ceramic fracture. This study aims to report the risk of revision for fracture of modern CoC bearings and identify factors that might influence this risk, using data from the National Joint Registry (NJR). Patients and Methods: We analysed data on 111,681 primary CoC THA’s and 182 linked revisions for bearing fracture recorded in NJR. We used implant codes to identify ceramic bearing composition and generated Kaplan-Meier estimates for implant survivorship. Logistic regression analyses were performed for implant size and patient specific variables to determine any associated risks for revision. Results: 99.8% of bearings were CeramTec Biolox® products. Revisions for fracture were linked to 7 of 79,442 (0.009%) Biolox® Delta heads, 38 of 31,982 (0.119%) Biolox® Forte heads, 101 of 80,170 (0.126%) Biolox® Delta liners and 35 of 31,258 (0.112%) Biolox® Forte liners. Regression analysis of implant size revealed smaller heads had significantly higher odds of fracture (χ2=68.0, p<0.0001). The highest fracture risk were observed in the 28mm Biolox® Forte subgroup (0.382%). There were no fractures in the 40mm head group for either ceramic type. Liner thickness was not predictive of fracture (p=0.67). BMI was independently associated with revision for both head fractures (OR 1.09 per unit increase, p=0.031) and liner fractures (OR 1.06 per unit increase, p=0.006). Conclusions: We report the largest study of CoC bearing fractures to date. The risk of revision for CoC bearing fracture is very low, however previous studies have underestimated this risk. There is good evidence that the latest generation of ceramic has greatly reduced the odds of head fracture but not of liner fracture. Small head size and high patient BMI are associated with an increased risk of ceramic bearing fracture

High-dose chemoradiotherapy followed by surgery versus surgery alone in esophageal cancer: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>We aimed to assess whether high-dose preoperative chemoradiotherapy (CRT) improves outcome in esophageal cancer patients compared to surgery alone and to define possible prognostic factors for overall survival.</p> <p>Methods</p> <p>Hundred-and-seven patients with disease stage IIA - III were treated with either surgery alone (n = 45) or high-dose preoperative CRT (n = 62). The data were collected retrospectively. Sixty-seven patients had adenocarcinomas, 39 squamous cell carcinomas and one undifferentiated carcinoma. CRT was given as three intensive chemotherapy courses by cisplatin 100 mg/m²on day 1 and 5-fluorouracil 1000 mg/m²/day, from day 1 through day 5 as continuous infusion. One course was given every 21 days. The last two courses were given concurrent with high-dose radiotherapy, 2 Gy/fraction and a median dose of 66 Gy. Kaplan-Meier survival analysis with log rank test was used to obtain survival data and Cox Regression multivariate analysis was used to define prognostic factors for overall survival.</p> <p>Results</p> <p>Toxicity grade 3 of CRT occurred in 30 (48.4%) patients and grade 4 in 24 (38.7%) patients of 62 patients. One patient died of neutropenic infection (grade 5). Fifty percent (31 patients) in the CRT group did undergo the planned surgery. Postoperative mortality rate was 9% and 10% in the surgery alone and CRT+ surgery groups, respectively (p = 1.0). Median overall survival was 11.1 and 31.4 months in the surgery alone and CRT+ surgery groups, respectively (log rank test, p = 0.042). In the surgery alone group one, 3 and 5 year survival rates were 44%, 24% and 16%, respectively and in the CRT+ surgery group they were 68%, 44% and 29%, respectively. By multivariate analysis we found that age of patient, performance status, alcoholism and > = 4 pathological positive lymph nodes in resected specimen were significantly associated with overall survival, whereas high-dose preoperative CRT was not.</p> <p>Conclusion</p> <p>We found no significant survival advantage in esophageal cancer stage IIA-III following preoperative high-dose CRT compared to surgery alone. Patient's age, performance status, alcohol abuse and number of positive lymph nodes were prognostic factors for overall survival.</p

Quality of life after curative gastrectomy for gastric cancer in a randomised controlled trial

Quality of life (QOL) was studied in gastric cancer patients treated on a randomised, controlled trial comparing D1 (level 1) with D3 (levels 1, 2 and 3) lymphadenectomy. A total of 221 patients were randomly assigned to D1 (n=110) and D3 (n=111) surgery. Quality-of-life assessments included functional outcomes (a 14-item survey about treatment-specific symptoms) and health perception (Spitzer QOL Index) was performed before and after surgery at disease-free status. Patients suffered from irrelative events such as loss of partners was excluded thereafter. Main analyses were done by intention-to-treat. Thus, 214 D1 (106/110=96.4%) and D3 (108/111=97.3%) R0 patients were assessed. Longitudinal analysis showed that functional outcomes decreased at 6 months after surgery and increased over time thereafter, while health perceptions increased over time in general. On the basis of linear mixed model analyses, patients having total gastrectomy, advanced cancer and hemipancreaticosplenectomy, but not complications had poorer QOL than those without. D1 and D3 patients showed no significant difference in QOL. The results suggest that changes of QOL were largely due to scope of gastric resection, disease status and distal pancreaticosplenectomy, rather than the extent of lymph node dissection. This indicates that nodal dissection can be performed for a potentially curable gastric cancer

Origin and insertion of the medial patellofemoral ligament: a systematic review of anatomy.

PURPOSE: The medial patellofemoral ligament (MPFL) is the major medial soft-tissue stabiliser of the patella, originating from the medial femoral condyle and inserting onto the medial patella. The exact position reported in the literature varies. Understanding the true anatomical origin and insertion of the MPFL is critical to successful reconstruction. The purpose of this systematic review was to determine these locations. METHODS: A systematic search of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed and Cochrane Library) and unpublished literature databases was conducted from their inception to the 3 February 2016. All papers investigating the anatomy of the MPFL were eligible. Methodological quality was assessed using a modified CASP tool. A narrative analysis approach was adopted to synthesise the findings. RESULTS: After screening and review of 2045 papers, a total of 67 studies investigating the relevant anatomy were included. From this, the origin appears to be from an area rather than (as previously reported) a single point on the medial femoral condyle. The weighted average length was 56 mm with an 'hourglass' shape, fanning out at both ligament ends. CONCLUSION: The MPFL is an hourglass-shaped structure running from a triangular space between the adductor tubercle, medial femoral epicondyle and gastrocnemius tubercle and inserts onto the superomedial aspect of the patella. Awareness of anatomy is critical for assessment, anatomical repair and successful surgical patellar stabilisation. LEVEL OF EVIDENCE: Systematic review of anatomical dissections and imaging studies, Level IV

The correspondence between the molecular orbital and differential ionization energies methods

The correspondence between Self-Consistent Hückel MO methods and Differential Ionization Energies methods is discussed in terms of the approximations used for the diagonal matrix elements. The two methods are shown to be equivalent if electronic correlation is neglected. Ground-state properties of the hydrogen halides are calculated by these simple methods and shown to be in good overall agreement with experimental data. Die Übereinstimmung zwischen selbstkonsistenten Hückel MO-Methoden und Methoden der Differentiellen Ionisierungsenergien wird in Termen solcher Näherungen diskutiert, die für die diagonalen Matrixelemente benutzt werden. Es wird gezeigt, daß die beiden Methoden äquivalent sind, wenn die Elektronenkorrelation vernachlässigt wird. Grundzustandseigenschaften der “hydrogen halides” werden mit diesen einfachen Methoden ausgerechnet und zeigen sich in überall guter Übereinstimmung mit experimentellen Daten. La correspondance entre les méthodes SCF Hückel et d'énergie d'ionisation différentielle est discutée en fonction des approximations utilisées pour les éléments de matrice diagonaux. Les deux méthodes sont équivalentes si la corrélation électronique est négligée. Les propriétés de l'état fondamental des acides halogènés sont calculées par ces méthodes simples et l'on constate un accord raisonnable avec les données expérimentales.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46451/1/214_2004_Article_BF00572780.pd