bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single column locking plate fixation is inadequate in two column acetabular fractures. A biomechanical analysis
Authors: Khajavi Kiarash , Lee Arthur T , Lindsey Derek P , Leucht Philipp , Bellino Michael J , Giori Nicholas J 
Published: May 2010

Abstract

Background
The objective of this study was to determine whether one can achieve stable fixation of a two column (transverse) acetabular fracture by only fixing a single column with a locking plate and unicortical locking screws. We hypothesized that a locking plate applied to the anterior column of a transverse acetabular fracture would create a construct that is more rigid than a non-locking plate, and that this construct would be biomechanically comparable to two column fixation.

Methods
Using urethane foam models of the pelvis, we simulated transverse acetabular fractures and stabilized them with 1) an anterior column plate with bicortical screws, 2) an anterior locking plate with unicortical screws, 3) an anterior plate and posterior column lag screw, and 4) a posterior plate with an anterior column lag screw. These constructs were mechanically loaded on a servohydraulic material testing machine. Construct stiffness and fracture displacement were measured.

Result and Discussion
We found that two column fixation is 54% stiffer than a single column fixation with a conventional plate with bicortical screws. There was no significant difference between fixation with an anterior column locking plate with unicortical screws and an anterior plate with posterior column lag screw. We detected a non-significant trend towards more stiffness for the anterior locking plate compared to the anterior non-locking plate.

Conclusion
In conclusion, a locking plate construct of the anterior column provides less stability than a traditional both column construct with posterior plate and anterior column lag screw. However, the locking construct offers greater strength than a non-locking, bicortical construct, which in addition often requires extensive contouring and its application is oftentimes accompanied by the risk of neurovascular damage.
Possible detection of cervical spondylotic neuropathy using Distribution of F-latency (DFL), a new neurophysiological parameter
Authors: Alam Mohammad J , Rabbani Khondkar S 
Published: May 2010

Abstract

Background
We have previously reported a new nerve conduction measurement parameter which we named the Distribution of F-latency (DFL) and showed that this was an approximate mirror of the Distribution of Conduction Velocity (DCV) of motor nerve fibers. This work was performed using measurements on the 20 median nerves from 10 volunteers. The DFL showed a number of different patterns including single peaks, broad peaks and double peaks, the latter observed on subjects with Cervical Spondylosis (CS). It was thought that a retrospective analysis of these data could be worthwhile in determining whether Cervical Spondylotic neuropathy could be detected using the DFL.

Findings
The DFL from the 8 median nerves of 4 normal subjects had single peaks, which has been assumed to represent a normal pattern. The DFL from one side of 5 subjects diagnosed with or suspected to have CS had double peaks. Broad peaks were observed in 7 nerves of which 5 were from subjects who had double peaks in the DFL on the contra lateral side.

Conclusions
Based on these findings, double peaks in the DFL appear to be associated with CS neuropathy. These findings further suggest that broad peaks in the DFL could indicate the early stages of the disease. Differential compression of nerve branches at the spinal roots are being explored as possible causes. This study does not preclude other pathologies contributing to double or broad peaks, but does suggest that the DFL could form a screening tool for CS neuropathy.
CaMKIV over-expression boosts cortical 4-7 Hz oscillations during learning and 1-4 Hz delta oscillations during sleep
Authors: Steenland Hendrik W , Wu Vincent , Fukushima Hotaka , Kida Satoshi , Zhuo Min 
Published: May 2010

Abstract
Mounting evidence suggests that neural oscillations are related to the learning and consolidation of newly formed memory in the mammalian brain. Four to seven Hertz (4-7 Hz) oscillations in the prefrontal cortex are also postulated to be involved in learning and attention processes. Additionally, slow delta oscillations (1-4 Hz) have been proposed to be involved in memory consolidation or even synaptic down scaling during sleep. The molecular mechanisms which link learning-related oscillations during wakefulness to sleep-related oscillations remain unknown. We show that increasing the expression of calcium/calmodulin dependent protein kinase IV (CaMKIV), a key nucleic protein kinase, selectively enhances 4-7.5 Hz oscillation power during trace fear learning and slow delta oscillations during subsequent sleep. These oscillations were found to be boosted in response to the trace fear paradigm and are likely to be localized to regions of the prefrontal cortex. Correlation analyses demonstrate that a proportion of the variance in 4-7.5 Hz oscillations, during fear conditioning, could account for some degree of learning and subsequent memory formation, while changes in slow delta power did not share this predictive strength. Our data emphasize the role of CaMKIV in controlling learning and sleep-related oscillations and suggest that oscillatory activity during wakefulness may be a relevant predictor of subsequent memory consolidation.
RNA interference suppression of mucin 5AC (MUC5AC) reduces the adhesive and invasive capacity of human pancreatic cancer cells
Authors: Yamazoe Sadaaki , Tanaka Hiroaki , Sawada Tetsuji , Amano Ryosuke , Yamada Nobuya , Ohira Masaichi , Hirakawa Kosei 
Published: May 2010

Abstract

Background
MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC de novo expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells.

Methods
We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si) RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells in vitro and in vivo. We compared parental cells (SW1990 and BxPC3) with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3).

Results
MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP) -3 and vascular endothelial growth factor (VEGF) were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. In vivo, si-SW1990 did not establish subcutaneous tumor in nude mice.

Conclusions
Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.
Breast cancer-specific mutations in CK1ε inhibit Wnt/β-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration
Authors: Foldynová-Trantírková Silvie , Sekyrová Petra , Tmejová Kateřina , Brumovská Eva , Bernatík Ondřej , Blankenfeldt Wulf , Krejčí Pavel , Kozubík Alois , Doležal Tomáš , Trantírek Lukáš , Bryja Vítězslav 
Published: May 2010

Abstract
Introduction
Breast cancer is one of the most common types of cancer in women. One of the genes that were found mutated in breast cancer is casein kinase 1 epsilon (CK1ε). Because CK1ε is a crucial regulator of the Wnt signaling cascades, we determined how these CK1ε mutations interfere with the Wnt pathway and affect the behavior of epithelial breast cancer cell lines.

Methods
We performed in silico modeling of various mutations and analyzed the kinase activity of the CK1ε mutants both in vitro and in vivo. Furthermore, we used reporter and small GTPase assays to identify how mutation of CK1ε affects different branches of the Wnt signaling pathway. Based on these results, we employed cell adhesion and cell migration assays in MCF7 cells to demonstrate a crucial role for CK1ε in these processes.

Results
In silico modeling and in vivo data showed that autophosphorylation at Thr 44, a site adjacent to the breast cancer point mutations in the N-terminal lobe of human CK1ε, is involved in positive regulation of the CK1ε activity. Our data further demonstrate that, in mammalian cells, mutated forms of CK1ε failed to affect the intracellular localization and phosphorylation of Dvl2; we were able to demonstrate that CK1ε mutants were unable to enhance Dvl-induced TCF/LEF-mediated transcription, that CK1ε mutants acted as loss-of-function in the Wnt/β-catenin pathway, and that CK1ε mutants activated the noncanonical Wnt/Rac-1 and NFAT pathways, similar to pharmacological inhibitors of CK1. In line with these findings, inhibition of CK1 promoted cell migration as well as decreased cell adhesion and E-cadherin expression in the breast cancer-derived cell line MCF7.

Conclusions
In summary, these data suggest that the mutations of CK1ε found in breast cancer can suppress Wnt/β-catenin as well as promote the Wnt/Rac-1/JNK and Wnt/NFAT pathways, thus contributing to breast cancer development via effects on cell adhesion and migration. In terms of molecular mechanism, our data indicate that the breast cancer point mutations in the N-terminal lobe of CK1ε, which are correlated with decreased phosphorylation activities of mutated forms of CK1ε both in vitro and in vivo, interfere with positive autophosphorylation at Thr 44.
Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators
Authors: Kollef Marin H , Nathwani Dilip , Merchant Sanjay , Gast Christopher , Quintana Alvaro , Ketter Nzeera 
Published: May 2010

Abstract
Introduction
Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, phase III studies, which also showed that doripenem was clinically noninferior to comparators.

Methods
We assessed durations of mechanical ventilation, intensive care unit (ICU) stay, and hospitalization in patients with VAP who received at least 1 dose of doripenem or a comparator in the phase III studies. Comparators were piperacillin/tazobactam (study 1) and imipenem (study 2). We analyzed between-group differences in medical resource utilization endpoints by comparison of Kaplan-Meier curves with generalized Wilcoxon test and in microbiologic eradication rates by two-sided Fisher's exact test.

Results
625 patients with VAP were evaluated and received at least 1 dose of doripenem (n = 312) or a comparator (n = 313). Median durations of mechanical ventilation (7 versus 10 days; P = 0.008) and hospitalization (22 versus 26 days; P = 0.010) were shorter for doripenem than comparators; corresponding ICU stays were 12 and 13 days (P = 0.065). All-cause, overall mortality rates were similar (51/312 [16%] versus 47/313 [15%]; P = 0.648). MIC90 values against Pseudomonas aeruginosa for doripenem versus imipenem were 4 versus 16 μg/mL in study 2. P. aeruginosa was eradicated from 16/24 (67%) doripenem recipients and 10/24 (42%) comparator recipients (P = 0.147). In patients with P. aeruginosa at baseline, median durations of mechanical ventilation (7 versus 13 days; P = 0.031) and ICU stay (13 versus 21 days; P = 0.027) were shorter for doripenem; corresponding hospital stays were 24 and 35 days (P = 0.129).

Conclusions
Doripenem was associated with lower medical resource utilization than comparators. Differences in antipseudomonal activity may have contributed to these findings.

Trial registration
ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).
Phase II Evaluation of Sorafenib in Advanced and Metastatic Squamous Cell Carcinoma of the Head and Neck: Southwest Oncology Group Study S0420
Authors: Williamson Stephen K. , Moon James , Huang Chao H. , Guaglianone Perry P. , LeBlanc Michael , Wolf Gregory T. , Urba Susan G. 
Published: May 2010

Purpose We conducted a phase II trial to evaluate the efficacy and safety of single-agent sorafenib in chemotherapy-naïve patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). The primary end point was response probability (ie, confirmed complete and partial response [PR]). Patients and Methods Chemotherapy-naïve patients with metastatic, persistent, or recurrent SCCHN who received one induction or fewer or received an adjuvant chemotherapy regimen, who had adequate organ function, and who had a performance status ≤ 1 were eligible. Sorafenib was administered orally at 400 mg twice daily on a continuous basis in 28-day cycles. Responses were evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors). Results Sorafenib was generally well tolerated. Of the 41 eligible patients assessed for adverse events, one experienced a grade 4 adverse event as a result of an asymptomatic pulmonary embolus. The most common grades 2 to 3 adverse events were fatigue, anorexia, stomatitis/oral pain, abdominal pain, hand-foot syndrome, weight loss, and hypertension. There was one confirmed PR and two unconfirmed PRs. The estimated confirmed response probability was 2% (95% CI, 0% to 13%). The estimated median progression-free survival was 4 months (95% CI, 2 to 4 months), and the estimated median overall survival was 9 months (95% CI, 7 to 14 months). Conclusion Sorafenib was well tolerated. Although response was poor, progression-free and overall survival times compare favorably with previous Southwest Oncology Group, phase II, single-agent trials.
Reliability of Human Epidermal Growth Factor Receptor 2 Immunohistochemistry in Breast Core Needle Biopsies
Authors: Lebeau Annette , Turzynski Andreas , Braun Susanne , Behrhof Wera , Fleige Barbara , Schmitt Wolfgang D. , Grob Tobias J. , Burkhardt Lia , Hölzel Dieter , Jackisch Christian , Thomssen Christoph , Müller Volkmar , Untch Michael 
Published: May 2010

Purpose Core needle biopsies (CNBs) are widely used to determine human epidermal growth factor receptor 2 (HER2) status in breast cancer. Recent publications reported up to 20% false-positive results on CNBs if immunohistochemistry (IHC) is compared with fluorescent in situ hybridization (FISH). To clarify, if confirmation of IHC positivity by FISH is generally required, we analyzed the reliability of IHC positivity on CNBs versus surgical specimens in a multi-institutional study. Patients and Methods Five pathologic laboratories contributed to this study by performing IHC on 500 CNBs and the corresponding surgical specimens overall. If IHC revealed score 2+ or 3+, HER2 status was confirmed by FISH in a central laboratory. We compared evaluation according to US Food and Drug Administration–approved scoring criteria and recently published American Society of Clinical Oncology (ASCO)–College of American Pathologists (CAP) guidelines. Results CNBs scored 3+ revealed five false-positive results if scoring followed the US Food and Drug Administration criteria (five of 40; 12.5%) and two false-positives in terms of the ASCO-CAP criteria (two of 33; 6.1%). IHC was false negative in one CNB only. By contrast, IHC on surgical specimens revealed five false-negative results, but only one false-positive result (one of 35; 2.9%) if scored following US Food and Drug Administration–approved criteria. With the aid of the ASCO-CAP criteria, false-positive IHC results were obtained in only one of the five participating institutions. Conclusion IHC 3+ scores on CNBs proved to be reliable in four of the five participating institutions if scoring followed the ASCO-CAP criteria. Therefore, accurate determination of HER2 status in breast cancer is possible on CNB using the common strategy to screen all cases by IHC and retest only 2+ scores by FISH. Prerequisites are quality assurance and the application of the new ASCO-CAP criteria.
Defective Mismatch Repair As a Predictive Marker for Lack of Efficacy of Fluorouracil-Based Adjuvant Therapy in Colon Cancer
Authors: Sargent Daniel J. , Marsoni Silvia , Monges Genevieve , Thibodeau Stephen N. , Labianca Roberto , Hamilton Stanley R. , French Amy J. , Kabat Brian , Foster Nathan R. , Torri Valter , Ribic Christine , Grothey Axel , Moore Malcolm , Zaniboni Alberto , Seitz Jean-Francois , Sinicrope Frank , Gallinger Steven 
Published: May 2010

Purpose Prior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mismatch repair (dMMR) have improved survival and receive no benefit from fluorouracil (FU) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair (pMMR) tumors. We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer. Methods MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU + levamisole or FU + leucovorin; n = 229) versus no postsurgical treatment (n = 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS). Results Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.93; P = .02) in patients with pMMR tumors. Patients with dMMR tumors receiving FU had no improvement in DFS (HR, 1.10; 95% CI, 0.42 to 2.91; P = .85) compared with those randomly assigned to surgery alone. In the pooled data set of 1,027 patients (n = 165 with dMMR), these findings were maintained; in patients with stage II disease and with dMMR tumors, treatment was associated with reduced overall survival (HR, 2.95; 95% CI, 1.02 to 8.54; P = .04). Conclusion Patient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy. These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making.
Value of wound biopsy in chronic venous ulceration
Authors: Miller D R , Enoch S , Williams D T , Price P E , Harding K G 
Published: May 2010

Objectives: Malignant transformation in chronic venous ulcers (CVU) is a limb threatening complication, which has an insidious onset. Clinical experience in our practice suggests a lack of suspicious macroscopic features making diagnosis difficult. The aim of this study is to evaluate the role of routine wound biopsy in the outpatient clinic for CVU without suspicious appearances but with no signs of healing despite appropriate treatment. Methods: A three-year (2000-2003) retrospective review of records for all patients who underwent biopsy of a CVU in the outpatient clinic in a specialist wound healing clinic set in a university hospital. Results: In our series ( n =76), three indications for biopsy were identified: CVU that had developed features suspicious of carcinoma ( n =17), CVU that had no suspicious features but were non-healing ( n =24) and CVU that had developed features of inflammatory ulceration ( n =35). A positive finding of carcinoma (squamous or basal cell carcinoma) or intraepidermal carcinoma (Bowen's disease) was made in four (24%), nine (37.5%) and 0 cases respectively. Conclusions: Malignancy may arise in CVU without showing suspicious features and wound biopsy should be advocated for any ulcer that fails to respond to appropriate treatment.
A comparison of physical methods for prophylaxis of deep vein thrombosis on augmentation of venous flow velocity and reduction of calf volume
Authors: Hirai M , Iwata H 
Published: May 2010

Objective: This study was designed to determine the optimal physical methods for promoting venous return of the leg. Methods: Ten healthy volunteers were investigated in the supine position on a couch, and their peak femoral venous velocity and calf muscle volume were determined using duplex ultrasound and strain gauge plethysmography,respectively,before and during deep respiration, limb elevation, calf squeezing and various types of leg exercises. Results: Deep respiration showed the smallest effect on both percentage increase of peak flow velocity and expelled volume. Elevation of the leg showed the same effect on the expelled volume as calf muscle squeezing and ankle movement, while the former showed significantly less effect than the latter on the percentage increase of peak flow velocity. In both dorsal flexion of the ankle and squeezing at the calf, the stronger of each procedure caused more effective changes in haemodynamics. Ankle exercise was more effective in promoting venous return in the calf muscle than wiggling the toes, making circling movements with the feet or alternately flexing and spreading the toes. Conclusions: Ankle exercise or calf muscle squeezing, performed maximally,may be the first recommendation for reducing venous stasis at the calf muscle and prophylaxis of deep vein thrombosis..
Attitudes toward autopsy in unexpected death: a nationwide survey of physicians and risk managers in Japanese teaching hospitals
Authors: Kamishiraki Etsuko , Maeda Shoichi , Starkey Jay , Ikeda Noriaki 
Published: May 2010

Context Autopsy is a useful tool for understanding the manner and cause of death in unexpected patient death. The information about the opinions of physicians and risk managers in Japan regarding autopsy is limited. Objective To describe and evaluate the opinions of physicians and risk managers at Japanese teaching hospitals regarding forensic autopsy. Design, setting and participants Cross-sectional study of all residency programme directors and risk managers completing a survey in January 2009. Specific clinical scenarios where autopsy would be essential to determine whether medical error occurred and whether medical care contributed to the death of the patient were presented. Respondents gave their opinion regarding the necessity of autopsy and their beliefs about if they would actually recommend it. Results Of 1113 eligible physicians and 1113 eligible chief risk management officers, 466 physicians (41.9%) and 599 risk managers (53.8%) responded. The majority of physicians and risk managers reported they would recommend an autopsy in cases of unclear medical error or unclear cause and effect relationship of medical care and patient death; however, 10% or more of physicians and 25% or more of risk managers (depending on the situation) reported that they would not recommend an autopsy. Risk managers were less likely than physicians to recommend and believe that autopsy was necessary. Conclusions The majority of physicians and risk managers in Japan would recommend autopsy and believe in its necessity in cases of unexpected patient death.