bluuebunny/crossref_metadata_2025 huggingface dataset:
Arthrofibrosis after TKA - Influence factors on the absolute flexion and gain in flexion after manipulation under anaesthesia
Authors: Ipach Ingmar , Mittag Falk , Lahrmann Julia , Kunze Beate , Kluba Torsten
Published: August 2011

Background

Stiffness with decreased range of motion (ROM) has been described as a frustrating complication after TKA. If all methods of physiotherapeutic treatment have been exhausted trying to develop ROM, manipulation under anaesthesia (MUA) can be discussed. The aim of the present study was to show the effect of MUA and to determine the influence of BMI, number of previous surgical procedures, pre-MUA ROM and timing of MUA for the results after MUA in regard to absolute flexion and gain in flexion.

Methods

858 patients underwent TKA at our institution between 2004 and 2009. 39 of these patients underwent MUA because of postoperative knee stiffness. The data were retrospective analysed for the influence of BMI, pre-MUA flexion (</≥ 70°), timing of MUA (>/≤ 30 days after TKA) and number of previous surgery on the results after MUA (absolute Flexion/gain in flexion).

Results

The prevalence for stiffness after TKA was 4.54%. There was a statistically significant improvement in flexion not only directly after MUA but also 6 weeks after MUA. Patients with two or more previous operations before TKA showed statistically significant worse results six weeks after MUA in absolute flexion and gain in flexion

(p = 0.039) than patients with one or two previous operations. No statistical significance in absolute flexion (p = 0.655) and gain in flexion (p = 0.328) after MUA between "early" and "late" was detected. The stiffer knees with a flexion below 70° showed significantly worse results (p = 0.044) in absolute flexion six weeks after MUA, but they also had statistical statistically better results with regard to gain in flexion (p ≤ 0.001).

Conclusion

MUA is a good instrument for improving ROM after TKA. The time between TKA and MUA seems less important, so different types of physiotherapeutic treatment could be tried before the procedure is started. MUA in patients with many previous operations and a flexion of less than 70° before MUA is not as effective as in other patients, but they also benefit from MUA.
The effects of laryngeal mask airway passage simulation training on the acquisition of undergraduate clinical skills: a randomised controlled trial
Authors: Laiou Elpiniki , Clutton-Brock Thomas H , Lilford Richard J , Taylor Celia A
Published: August 2011

Background

Effective use of the laryngeal mask airway (LMA) requires learning proper insertion technique in normal patients undergoing routine surgical procedures. However, there is a move towards simulation training for learning practical clinical skills, such as LMA placement. The evidence linking different amounts of mannequin simulation training to the undergraduate clinical skill of LMA placement in real patients is limited. The purpose of this study was to compare the effectivenessin vivoof two LMA placement simulation courses of different durations.

Methods

Medical students (n = 126) enrolled in a randomised controlled trial. Seventy-eight of these students completed the trial. The control group (n = 38) received brief mannequin training while the intervention group (n = 40) received additional more intensive mannequin training as part of which they repeated LMA insertion until they were proficient. The anaesthetists supervising LMA placements in real patients rated the participants' performance on assessment forms. Participants completed a self-assessment questionnaire.

Results

Additional mannequin training was not associated with improved performance (37% of intervention participants received an overall placement rating of > 3/5 on their first patient compared to 48% of the control group, X2= 0.81, p = 0.37). The agreement between the participants and their instructors in terms of LMA placement success rates was poor to fair. Participants reported that mannequins were poor at mimicking reality.

Conclusions

The results suggest that the value of extended mannequin simulation training in the case of LMA placement is limited. Educators considering simulation for the training of practical skills should reflect on the extent to which thein vitrosimulation mimics the skill required and the degree of difficulty of the procedure.
Relationship between lipid profiles and plasma total homocysteine, cysteine and the risk of coronary artery disease in coronary angiographic subjects
Authors: Xiao Yunjun , Zhang Yuan , Lv Xiaofei , Su Dongfang , Li Dan , Xia Min , Qiu Jian , Ling Wenhua , Ma Jing
Published: August 2011

Background

Homocysteine and cysteine are considered as risk factors of cardiovascular disease. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice model. We aimed therefore to evaluate whether homocysteine and cysteine are associated with lipid parameters, and the joint effects of them on the risk of coronary artery disease (CAD). Plasma total homocysteine (tHcy), cysteine (tCys) and lipid markers were measured in 2058 consecutive coronary artery angiographic patients.

Results

Plasma tHcy but not tCys correlated negatively with ApoA-I (r = -0.153, P < 0.001) and with HDL cholesterol (r = -0.148, P < 0.001), and correlated positively with the risk of CAD (OR: 1.61; 95% confidence interval; 1.26 to 2.05). Combination of high tHcy and high tCys levels was associated with decreased ApoA-I and HDL cholesterol levels, and with increased risk of CAD (OR: 1.696, 95% CI (1.301-2.211)). Furthermore, low HDL cholesterol combined with low tHcy or high tHcy all had increased risk for CAD (OR: 1.254, 95% CI (1.114-1.565); OR: 1.332, 95% CI (1.093-1.624); respectively) whereas high HDL cholesterol counteracted the harmful effect of high tHcy on the risk of CAD. However, only the combination of high tHcy and high ApoA-I had an increased risk for CAD (OR: 1.438, 95% CI (1.170-1.768)).

Conclusions

The association of homocysteine and cysteine, ApoA-I or HDL cholesterol and their joint effects provide new insights on its role on CAD.
Decreased levels of genuine large free hCG alpha in men presenting with abnormal semen analysis
Authors: Zenzmaier Christoph , Gerth Regine , Gruschwitz Matthias , Lindner Herbert , Plas Eugen , Berger Peter
Published: August 2011

Background

The pregnancy hormone human chorionic gonadotropin (hCG) and its free subunits (hCG alpha, hCG beta) are produced in the male reproductive tract and found in high concentrations in seminal fluid, in particular hCG alpha. This study aimed to elucidate changes in peptide hormone profiles in patients showing abnormal semen analyses and to determine the genuineness of the highly abundant hCG alpha.

Methods

Seminal plasma was obtained from 45 male patients undergoing semen analysis during infertility workups. Comprehensive peptide hormone profiles were established by a panel of immunofluorometric assays for hCG, hCG alpha, hCG beta and its metabolite hCG beta core fragment, placental lactogen, growth hormone and prolactin in seminal plasma of patients with abnormal semen analysis results (n = 29) versus normozoospermic men (n = 16). The molecular identity of large hyperglycosylated hCG alpha was analyzed by mass-spectrometry and selective deglycosylation.

Results

hCG alpha levels were found to be significantly lower in men with impaired semen quality (1346 +/- 191 vs. 2753 +/- 533 ng/ml, P = 0.022). Moreover, patients with reduced sperm count had reduced intact hCG levels compared with normozoospermic men (0.097 +/- 0.022 vs. 0.203 +/- 0.040 ng/ml, P = 0.028). Using mass-spectrometry, the biochemical identity of hCG alpha purified from seminal plasma was verified. Under non-reducing conditions in SDS-PAGE, hCG alpha isolated from seminal plasma migrated in a manner comparable with large free hCG alpha with an apparent molecular mass (Mr, app) of 24 kDa, while hCG alpha dissociated from pregnancy-derived holo-hCG migrated at approximately 22 kDa. After deglycosylation with PNGase F under denaturing conditions, all hCG alpha variants showed an Mr, app of 15 kDa, indicating identical amino acid backbones.

Conclusions

The findings indicate a pathophysiological relevance of hCG, particularly its free alpha subunit, in spermatogenesis. The alternative glycosylation pattern on the free large hCG alpha in seminal plasma might reflect a modified function of this subunit in the male reproductive tract.
SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice
Authors: Shin Jin-Hong , Bostick Brian , Yue Yongping , Hajjar Roger , Duan Dongsheng
Published: August 2011

Background

Cardiomyocyte calcium overloading has been implicated in the pathogenesis of Duchenne muscular dystrophy (DMD) heart disease. The cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a major role in removing cytosolic calcium during heart muscle relaxation. Here, we tested the hypothesis that SERCA2a over-expression may mitigate electrocardiography (ECG) abnormalities in old female mdx mice, a murine model of DMD cardiomyopathy.

Methods

1 × 1012 viral genome particles/mouse of adeno-associated virus serotype-9 (AAV-9) SERCA2a vector was delivered to 12-m-old female mdx mice (N = 5) via a single bolus tail vein injection. AAV transduction and the ECG profile were examined eight months later.

Results

The vector genome was detected in the hearts of all AAV-injected mdx mice. Immunofluorescence staining and western blot confirmed SERCA2a over-expression in the mdx heart. Untreated mdx mice showed characteristic tachycardia, PR interval reduction and QT interval prolongation. AAV-9 SERCA2a treatment corrected these ECG abnormalities.

Conclusions

Our results suggest that AAV SERCA2a therapy may hold great promise in treating dystrophin-deficient heart disease.
Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer
Authors: Elfiky Aymen A , Aziz Saadia A , Conrad Patricia J , Siddiqui Summar , Hackl Wolfgang , Maira Michel , Robert Camp L , Kluger Harriet M
Published: August 2011

Background

PI3K and mTOR are key components of signal transduction pathways critical for cell survival. Numerous PI3K inhibitors have entered clinical trials, while mTOR is the target of approved drugs for metastatic renal cell carcinoma (RCC). We characterized expression of p85 and p110α PI3K subunits and mTOR in RCC specimens and assessed pharmacologic co-targeting of these molecules in vitro.

Methods

We employed tissue microarrays containing 330 nephrectomy cases using a novel immunofluorescence-based method of Automated Quantitative Analysis (AQUA) of in situ protein expression. In RCC cell lines we assessed synergism between PI3K and mTOR inhibitors and activity of NVP-BEZ235, which co-targets PI3K and mTOR.

Results

p85 expression was associated with high stage and grade (P < 0.0001 for both). High p85 and high mTOR expression were strongly associated with decreased survival, and high p85 was independently prognostic on multi-variable analysis. Strong co-expression of both PI3K subunits and mTOR was found in the human specimens. The PI3K inhibitor LY294002 and rapamycin were highly synergistic in all six RCC cell lines studied. Similar synergism was seen with all rapamycin concentrations used. NVP-BEZ235 inhibited RCC cell growth in vitro with IC50s in the low ηM range and resultant PARP cleavage.

Conclusions

High PI3K and mTOR expression in RCC defines populations with decreased survival, suggesting that they are good drug targets in RCC. These targets tend to be co-expressed, and co-targeting these molecules is synergistic. NVP-BEZ235 is active in RCC cells in vitro; suggesting that concurrent PI3K and mTOR targeting in RCC warrants further investigation.
Partial response to anakinra in life-threatening Henoch-Schönlein purpura: case report
Authors: Boyer Erynn M , Turman Martin , O'Neil Kathleen M
Published: August 2011

Henoch-Schönlein purpura is one of the most common forms of systemic vasculitis of childhood. We report the response to anakinra, the interleukin-1 receptor antagonist, in a 9 year old girl without prior medical problems who developed life-threatening Henoch-Schönlein vasculitis that produced renal failure, pulmonary hemorrhage and vasculitis of the brain. Her response supports the theory that interleukin-1 may be an important mediator in this disease. Further study of interleukin-1 antagonists in severe Henoch-Schönlein purpura may be warranted.
Radial breathing mode of carbon nanotubes subjected to axial pressure
Authors: Lei Xiao-Wen , Ni Qing-Qing , Shi Jin-Xing , Natsuki Toshiaki
Published: August 2011

In this paper, a theoretical analysis of the radial breathing mode (RBM) of carbon nanotubes (CNTs) subjected to axial pressure is presented based on an elastic continuum model. Single-walled carbon nanotubes (SWCNTs) are described as an individual elastic shell and double-walled carbon nanotubes (DWCNTs) are considered to be two shells coupled through the van der Waals force. The effects of axial pressure, wave numbers and nanotube diameter on the RBM frequency are investigated in detail. The validity of these theoretical results is confirmed through the comparison of the experiment, calculation and simulation. Our results show that the RBM frequency is linearly dependent on the axial pressure and is affected by the wave numbers. We concluded that RBM frequency can be used to characterize the axial pressure acting on both ends of a CNT.
Adaptive antenna selection and Tx/Rx beamforming for large-scale MIMO systems in 60 GHz channels
Authors: Dong Ke , Prasad Narayan , Wang Xiaodong , Zhu Shihua
Published: August 2011

We consider a large-scale MIMO system operating in the 60 GHz band employing beamforming for high-speed data transmission. We assume that the number of RF chains is smaller than the number of antennas, which motivates the use of antenna selection to exploit the beamforming gain afforded by the large-scale antenna array. However, the system constraint that at the receiver, only a linear combination of the receive antenna outputs is available, which together with the large dimension of the MIMO system makes it challenging to devise an efficient antenna selection algorithm. By exploiting the strong line-of-sight property of the 60 GHz channels, we propose an iterative antenna selection algorithm based on discrete stochastic approximation that can quickly lock onto a near-optimal antenna subset. Moreover, given a selected antenna subset, we propose an adaptive transmit and receive beamforming algorithm based on the stochastic gradient method that makes use of a low-rate feedback channel to inform the transmitter about the selected beams. Simulation results show that both the proposed antenna selection and the adaptive beamforming techniques exhibit fast convergence and near-optimal performance.
Systems of general nonlinear set-valued mixed variational inequalities problems in Hilbert spaces
Authors: Agarwal Ravi P , Cho Yeol JE , Petrot Narin
Published: August 2011

In this paper, the existing theorems and methods for finding solutions of systems of general nonlinear set-valued mixed variational inequalities problems in Hilbert spaces are studied. To overcome the difficulties, due to the presence of a proper convex lower semi-continuous function, φ and a mapping g, which appeared in the considered problem, we have used some applications of the resolvent operator technique. We would like to point out that although many authors have proved results for finding solutions of the systems of nonlinear set-valued (mixed) variational inequalities problems, it is clear that it cannot be directly applied to the problems that we have considered in this paper because of φ and g.

2000 AMS Subject Classification: 47H05; 47H09; 47J25; 65J15.
Identification of specificity determining residues in peptide recognition domains using an information theoretic approach applied to large-scale binding maps
Authors: Yip Kevin Y , Utz Lukas , Sitwell Simon , Hu Xihao , Sidhu Sachdev S , Turk Benjamin E , Gerstein Mark , Kim Philip M
Published: August 2011

Background

Peptide Recognition Domains (PRDs) are commonly found in signaling proteins. They mediate protein-protein interactions by recognizing and binding short motifs in their ligands. Although a great deal is known about PRDs and their interactions, prediction of PRD specificities remains largely an unsolved problem.

Results

We present a novel approach to identifying these Specificity Determining Residues (SDRs). Our algorithm generalizes earlier information theoretic approaches to coevolution analysis, to become applicable to this problem. It leverages the growing wealth of binding data between PRDs and large numbers of random peptides, and searches for PRD residues that exhibit strong evolutionary covariation with some positions of the statistical profiles of bound peptides. The calculations involve only information from sequences, and thus can be applied to PRDs without crystal structures. We applied the approach to PDZ, SH3 and kinase domains, and evaluated the results using both residue proximity in co-crystal structures and verified binding specificity maps from mutagenesis studies.

Discussion

Our predictions were found to be strongly correlated with the physical proximity of residues, demonstrating the ability of our approach to detect physical interactions of the binding partners. Some high-scoring pairs were further confirmed to affect binding specificity using previous experimental results. Combining the covariation results also allowed us to predict binding profiles with higher reliability than two other methods that do not explicitly take residue covariation into account.

Conclusions

The general applicability of our approach to the three different domain families demonstrated in this paper suggests its potential in predicting binding targets and assisting the exploration of binding mechanisms.
Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration
Authors: Bai Siau Wei , Herrera-Abreu Maria Teresa , Rohn Jennifer L , Racine Victor , Tajadura Virginia , Suryavanshi Narendra , Bechtel Stephanie , Wiemann Stefan , Baum Buzz , Ridley Anne J
Published: August 2011

Background

Cell migration is essential during development and in human disease progression including cancer. Most cell migration studies concentrate on known or predicted components of migration pathways.

Results

Here we use data from a genome-wide RNAi morphology screen in Drosophila melanogaster cells together with bioinformatics to identify 26 new regulators of morphology and cytoskeletal organization in human cells. These include genes previously implicated in a wide range of functions, from mental retardation, Down syndrome and Huntington's disease to RNA and DNA-binding genes. We classify these genes into seven groups according to phenotype and identify those that affect cell migration. We further characterize a subset of seven genes, FAM40A, FAM40B, ARC, FMNL3, FNBP3/FBP11, LIMD1 and ZRANB1, each of which has a different effect on cell shape, actin filament distribution and cell migration. Interestingly, in several instances closely related isoforms with a single Drosophila homologue have distinct phenotypes. For example, FAM40B depletion induces cell elongation and tail retraction defects, whereas FAM40A depletion reduces cell spreading.

Conclusions

Our results identify multiple regulators of cell migration and cytoskeletal signalling that are highly conserved between Drosophila and humans, and show that closely related paralogues can have very different functions in these processes.
Phylogenetic exploration of hantaviruses in paraguay reveals reassortment and host switching in South America
Authors: Chu Yong-Kyu , Owen Robert D , Jonsson Colleen B
Published: August 2011

Background

Longitudinal mark-recapture studies of rodents in two sites in the Mbaracayú Biosphere Reserve in the Interior Atlantic Forest of eastern Paraguay have revealed a complex and intriguing pattern of hantaviruses harbored by rodents in this area. Full-length sequencing and phylogenetic analyses were conducted for several rodents from Akodon montensis and Oligoryzomys fornesi. The phylogenetic relationships of these viruses were analyzed in the context of hantaviruses in South America with published S- and M-segment sequences.

Findings

Phylogenetic analyses of hantaviruses identified in the Mbaracayú Biosphere Reserve in Paraguay revealed Jabora and Juquitiba viruses are harbored by Akodon montensis and Oligoryzomys fornesi, respectively. These analyses revealed that in general the constituents of the major subclade for the S- and M-segments differ for the South American hantaviruses. Further, the two major groups within subclade C for the M-segment reflect in general the lethality associated with the viruses within each group.

Conclusions

Phylogenetic studies of Jabora and Juquitiba viruses and other Paraguayan viruses in the context of American hantaviruses revealed reassortment and host-switching in the evolution of South American hantaviruses.
Improving hypertension management through pharmacist prescribing; the rural alberta clinical trial in optimizing hypertension (Rural RxACTION): trial design and methods
Authors: Charrois Theresa L , McAlister Finlay A , Cooney Dale , Lewanczuk Richard , Kolber Michael R , Campbell Norman RC , Rosenthal Meagen , Houle Sherilyn KD , Tsuyuki Ross T
Published: August 2011

Background

Patients with hypertension continue to have less than optimal blood pressure control, with nearly one in five Canadian adults having hypertension. Pharmacist prescribing is gaining favor as a potential clinically efficacious and cost-effective means to improve both access and quality of care. With Alberta being the first province in Canada to have independent prescribing by pharmacists, it offers a unique opportunity to evaluate outcomes in patients who are prescribed antihypertensive therapy by pharmacists.

Methods

The study is a randomized controlled trial of enhanced pharmacist care, with the unit of randomization being the patient. Participants will be randomized to enhanced pharmacist care (patient identification, assessment, education, close follow-up, and prescribing/titration of antihypertensive medications) or usual care. Participants are patients in rural Alberta with undiagnosed/uncontrolled blood pressure, as defined by the Canadian Hypertension Education Program. The primary outcome is the change in systolic blood pressure between baseline and 24 weeks in the enhanced-care versus usual-care arms. There are also three substudies running in conjunction with the project examining different remuneration models, investigating patient knowledge, and assessing health-resource utilization amongst patients in each group.

Discussion

To date, one-third of the required sample size has been recruited. There are 15 communities and 17 pharmacists actively screening, recruiting, and following patients. This study will provide high-level evidence regarding pharmacist prescribing.

Trial Registration

Clinicaltrials.gov NCT00878566.
Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan
Authors: Lee Ching-Chih , Huang Tze-Ta , Lee Moon-Sing , Su Yu-Chieh , Chou Pesus , Hsiao Shih-Hsuan , Chiou Wen-Yen , Lin Hon-Yi , Chien Sou-Hsin , Hung Shih-Kai
Published: August 2011

Background

Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC.

Methods

Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads.

Results

As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p < 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p < 0.001).

Conclusions

Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.
Early results of quality of life for curatively treated rectal cancers in Chinese patients with EORTC QLQ-CR29
Authors: Peng Junjie , Shi Debing , Goodman Karyn A , Goldstein David , Xiao Changchun , Guan Zuqing , Cai Sanjun
Published: August 2011

Purpose

To assess the quality of life in curatively treated patients with rectal cancer in a prospectively collected cohort.

Methods

Patients with stage I-III rectal cancer who were treated curatively in a single institution were accrued prospectively. Quality of life was assessed by use of the European Organization for Research and Treatment of Cancer questionnaire module for all cancer patients (QLQ-C30) and for colorectal cancer patients (QLQ-CR29). Quality of life among different treatment modalities and between stoma and nonstoma patients was evaluated in all patients.

Results

A total of 154 patients were assessed. The median time of completion for the questionnaires was 10 months after all the treatments. For patients with different treatment modalities, faecal incontinence and diarrhea were significantly higher in radiation group (p = 0.002 and p = 0.001, respectively), and no difference in male or female sexual function was found between radiation group and non-radiation group. For stoma and nonstoma patients, the QLQ-CR29 module found the symptoms of Defaecation and Embarrassment with Bowel Movement were more prominent in stoma patients, while no difference was detected in scales QLQ-C30 module.

Conclusions

Our study provided additional information in evaluating QoL of Chinese rectal cancer patients with currently widely used QoL questionnaires. As a supplement to the QLQ-C30, EORTC QLQ-CR29 is a useful questionnaire in evaluating curatively treated patients with rectal cancer. Bowel dysfunction (diarrhea and faecal incontinence) was still the major problem compromising QoL in patients with either pre- or postoperative chemoradiotherapy.
Rare association between cystic fibrosis, Chiari I malformation, and hydrocephalus in a baby: a case report and review of the literature
Authors: Patel Akash J , Raol Viraj H , Jea Andrew
Published: August 2011

Introduction

Cystic fibrosis, an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator gene, is not generally associated with malformations of the central nervous system. We review eight previously published reports detailing an infrequent association between cystic fibrosis and Chiari I malformation.

Case presentation

To the best of our knowledge, our report describes only the ninth case of a baby presenting with a new diagnosis of cystic fibrosis and Chiari I malformation, in this case in a 10-month-old, full-term Caucasian baby boy from the United States of America. Neurosurgical consultation was obtained for associated developmental delay, macrocephaly, bulging anterior fontanel, and papilledema. An MRI scan demonstrated an extensive Chiari I malformation with effacement of the fourth ventricle, obliteration of the outlets of the fourth ventricle and triventricular hydrocephalus without aqueductal stenosis. Our patient was taken to the operating room for ventriculoperitoneal shunt placement.

Conclusions

It is possible that the cystic fibrosis transmembrane conductance regulator gene may play a previously unrecognized role in central nervous system development; alternatively, this central nervous system abnormality may have been acquired due to constant valsalva from recurrent coughing or wheezing or metabolic and electrolyte imbalances that occur characteristically in cystic fibrosis.
Torsades de pointes during laparoscopic adrenalectomy of a pheochromocytoma: a case report
Authors: van der Heide Kinge , de Haes Ann , Wietasch Götz JK , Wiesfeld Ans CP , Hendriks Herman GD
Published: August 2011

Introduction

Torsades de pointes is a rare but potentially lethal arrhythmia. The amount of literature available on Torsades de pointes occurring in patients with pheochromocytoma is limited, and we found no literature describing this dysrhythmia in a patient with pheochromocytoma under anesthesia.

Case presentation

We describe the case of a 42-year-old Caucasian woman without QT prolongation preoperatively with recurrent Torsades de pointes during laparoscopic removal of a pheochromocytoma. Torsades de pointes mainly occurs in the setting of a prolonged QT interval. This patient neither had a prolonged QT preoperatively nor was her family history suspect for a congenital long QT syndrome. Most likely, our patient had an acquired long QT syndrome, elicited by the combination of flecainide, hypomagnesemia and adrenergic stimulation during manipulation of the tumor.

Conclusion

We show that in the case of a surgical pheochromocytoma removal, perioperative conditions can elicit an acquired or previously unknown congenital long QT syndrome. Therefore, preoperative α- and β-blockade is advised, QT-prolonging drugs should be avoided and potassium and magnesium plasma levels should be kept at normal to high levels.
Steinert's syndrome presenting as anal incontinence: a case report
Authors: Erdenen Fusun , Toros Ahmet Burak , Uzum Ayse Kubat , Sacak Sirin
Published: August 2011

Introduction

Myotonic dystrophy (MD) or Steinert's syndrome is a rare cause of chronic diarrhea and anal incontinence. In the presence of chronic diarrhea and fecal incontinence with muscle weakness, neuromuscular disorders such as myotonic dystrophy should be considered in the differential diagnosis.

Case Presentation

We present the case of a 45-year-old Turkish man with Steinert's syndrome, who was not diagnosed until the age of 45.

Conclusions

In clinical practice, the persistence of diarrhea and fecal incontinence with muscle weakness should suggest that the physician perform an anal manometric study and electromyography. Neuromuscular disorders such as myotonic dystrophy should be considered in the differential diagnosis.
Inspiratory muscle training to facilitate weaning from mechanical ventilation: protocol for a systematic review
Authors: Moodie Lisa H , Reeve Julie C , Vermeulen Niki , Elkins Mark R
Published: August 2011

Background

In intensive care, weaning is the term used for the process of withdrawal of mechanical ventilation to enable spontaneous breathing to be re-established. Inspiratory muscle weakness and deconditioning are common in patients receiving mechanical ventilation, especially that of prolonged duration. Inspiratory muscle training could limit or reverse these unhelpful sequelae and facilitate more rapid and successful weaning.

Methods

This review will involve systematic searching of five electronic databases to allow the identification of randomised trials of inspiratory muscle training in intubated and ventilated patients. From these trials, we will extract available data for a list of pre-defined outcomes, including maximal inspiratory pressure, the duration of the weaning period, and hospital length of stay. We will also meta-analyse comparable results where possible, and report a summary of the available pool of evidence.

Discussion

The data generated by this review will be the most comprehensive answer available to the question of whether inspiratory muscle training is clinically useful in intensive care. As well as informing clinicians in the intensive care setting, it will also inform healthcare managers deciding whether health professionals with skills in respiratory therapy should be made available to provide this sort of intervention. Through the publication of this protocol, readers will ultimately be able to assess whether the review was conducted according to a pre-defined plan. Researchers will be aware that the review is underway, thereby avoid duplication, and be able to use it as a basis for planning similar reviews.
Lipohypertrophy in children and adolescents with type 1 diabetes and the associated factors
Authors: Omar Magdy A , El-Kafoury Ahmed A , El-Araby Ramy I
Published: August 2011

Background

Despite the important implications of lipohypertrophy for diabetes control, there is a dearth of information and research about the subject in children. The aim of this study was to study the prevalence of lipohypertrophy in children with type 1 diabetes, and to evaluate the associated factors.

Findings

119 children coming for regular follow up in the diabetes clinic were examined for the presence of lipohypertrophy by inspection and palpation. The last 4 readings of glycated hemoglobin (HbA1c) levels and other factors that may affect lipohypertrophy were documented. RESULTS: The patient's age ranged from 2 months to 21 years with a median of 10 years (inter-quartile range = 6). Lipohypertrophy occurred in 54.9% of patients, more commonly in males (62.7%) vs. females (48.4%) (P = 0.074). Grade 1 lipohypertrophy occurred in 42.5% and grade 2 in 12.4%. Lipohypertrophy was related significantly to the dose of insulin units per kg of body weight (Odds ratio [OR] = 16.4; 95% CI, 2.2 - 124.6; P = 0.007), the duration of diabetes, [OR] = 1.16; 95% CI, 1.05 - 1.32; P = 0.004)), and the body mass index (BMI) [OR] = 1.68; 95% CI, 1.25 - 2.15; P = 0.006). The mean HbA1c levels of patients with grade 1 and grade 2 lipohypertrophy did not differ from diabetics without lipohypertrophy (F = 0.178, P = 0.837)

Conclusions

The presence of lipohypertrophy was significantly associated with the duration of diabetes and the body mass index. Children with lipohypertrophy needed a significantly higher dose of insulin units/kg of body weight to achieve fair control compared to children without lipohypertrophy. Further studies are needed to ascertain the clinical meaning of these findings.
Alcohol promotes breast cancer cell invasion by regulating the Nm23-ITGA5 pathway
Authors: Wong Amy W , Paulson Qiwei X , Hong Jina , Stubbins Renee E , Poh Karen , Schrader Emily , Nunez Nomeli P
Published: August 2011

Background

Alcohol consumption is an established risk factor for breast cancer metastasis. Yet, the mechanism by which alcohol promotes breast cancer metastases is unknown. The ability of cancer cells to invade through tissue barriers (such as basement membrane and interstitial stroma) is an essential step towards establishing cancer metastasis. In the present study, we identify and examine the roles of two genes, Nm23 and ITGA5, in alcohol-induced breast cancer cell invasion.

Methods

Human breast cancer T47D cells were treated with ethanol at various concentrations. Boyden chamber invasion assays were used to measure cellular invasive ability. The mRNA expression level of metastasis suppressor genes including Nm23 was determined by qRT-PCR. ITGA5 was identified using a qRT-PCR array of 84 genes important for cell-cell and cell-extracellular matrix interactions. Nm23 overexpression in addition to Nm23- and ITGA5 knock-down were used to determine the role of the Nm23-ITGA5 pathway on cellular invasive ability of T47D cells. Protein expression levels were verified by Western blot.

Results

Alcohol increased the invasive ability of human breast cancer T47D cells in a dose-dependent manner through the suppression of the Nm23 metastatic suppressor gene. In turn, Nm23 down-regulation increased expression of fibronectin receptor subunit ITGA5, which subsequently led to increased cellular invasion. Moreover, Nm23 overexpression was effective in suppressing the effects of alcohol on cell invasion. In addition, we show that the effects of alcohol on invasion were also inhibited by knock-down of ITGA5.

Conclusions

Our results suggest that the Nm23-ITGA5 pathway plays a critical role in alcohol-induced breast cancer cell invasion. Thus, regulation of this pathway may potentially be used to prevent the establishment of alcohol-promoted metastases in human breast cancers.
Dosimetric impact of target definitions on normal structures in head and neck cancer
Authors: Monaghan Micah T , Bonner James A , Schaner Philip E , Caudell Jimmy J
Published: August 2011

Background and Purpose

Previous work by our group suggests smaller target volumes may result in equivalent locoregional control for head and neck cancer. We evaluated whether smaller target volumes may also result in improved normal tissue sparing.

Methods and Materials

Ten patients with Stage III-IV head and neck cancer were contoured and planned according to target definitions in RTOG 0522 in a two dose level plan (RTOG), as well as a three dose level plan, using smaller target volumes and an intermediate dose prescription (3Dose). Plans were compared for coverage of targets and sparing of normal tissues

Results

The high dose target, elective nodal target, and total volume targeted were significantly smaller in 3Dose plans (p < 0.001). There was no difference in volume receiving 100% of each prescription level in RTOG or 3Dose plans. Mean dose to contralateral parotid, mandible, larynx, and inferior pharyngeal constrictor, and maximum dose to brainstem were significantly lower in 3Dose plans. There was no significant difference in maximum dose to spinal cord or volume of tissue not otherwise specified receiving 70 Gy.

Conclusions

Smaller target volumes with the addition of an intermediate dose volume results in improved sparing of most normal tissues.
Cellular Senescence - its role in cancer and the response to ionizing radiation
Authors: Sabin Rebecca J , Anderson Rhona M
Published: August 2011

Cellular senescence is a normal biological process that is initiated in response to a range of intrinsic and extrinsic factors that functions to remove irreparable damage and therefore potentially harmful cells, from the proliferative pool. Senescence can therefore be thought of in beneficial terms as a tumour suppressor. In contrast to this, there is a growing body of evidence suggesting that senescence is also associated with the disruption of the tissue microenvironment and development of a pro-oncogenic environment, principally via the secretion of senescence-associated pro-inflammatory factors. The fraction of cells in a senescent state is known to increase with cellular age and from exposure to various stressors including ionising radiation therefore, the implications of the detrimental effects of the senescent phenotype are important to understand within the context of the increasing human exposure to ionising radiation. This review will discuss what is currently understood about senescence, highlighting possible associations between senescence and cancer and, how exposure to ionising radiation may modify this.
The ING tumor suppressors in cellular senescence and chromatin
Authors: Ludwig Susann , Klitzsch Alexandra , Baniahmad Aria
Published: August 2011

The Inhibitor of Growth (ING) proteins represent a type II tumor suppressor family comprising five conserved genes, ING1 to ING5. While ING1, ING2 and ING3 proteins are stable components of the mSIN3a-HDAC complexes, the association of ING1, ING4 and ING5 with HAT protein complexes was also reported. Among these the ING1 and ING2 have been analyzed more deeply. Similar to other tumor suppressor factors the ING proteins are also involved in many cellular pathways linked to cancer and cell proliferation such as cell cycle regulation, cellular senescence, DNA repair, apoptosis, inhibition of angiogenesis and modulation of chromatin.

A common structural feature of ING factors is the conserved plant homeodomain (PHD), which can bind directly to the histone mark trimethylated lysine of histone H3 (H3K4me3). PHD mutants lose the ability to undergo cellular senescence linking chromatin mark recognition with cellular senescence. ING1 and ING2 are localized in the cell nucleus and associated with chromatin modifying enzymes, linking tumor suppression directly to chromatin regulation. In line with this, the expression of ING1 in tumors is aberrant or identified point mutations are mostly localized in the PHD finger and affect histone binding. Interestingly, ING1 protein levels increase in replicative senescent cells, latter representing an efficient pathway to inhibit cancer proliferation. In association with this, suppression of p33ING1 expression prolongs replicative life span and is also sufficient to bypass oncogene-induced senescence. Recent analyses of ING1- and ING2-deficient mice confirm a tumor suppressive role of ING1 and ING2 and also indicate an essential role of ING2 in meiosis.

Here we summarize the activity of ING1 and ING2 as tumor suppressors, chromatin factors and in development.
Modulation of interleukin-1β-induced inflammatory responses by a synthetic cationic innate defence regulator peptide, IDR-1002, in synovial fibroblasts
Authors: Turner-Brannen Emily , Choi Ka-Yee , Lippert Dustin ND , Cortens John P , Hancock Robert EW , El-Gabalawy Hani , Mookherjee Neeloffer
Published: August 2011

Introduction

Innate defence regulator (IDR) peptides are synthetic cationic peptides, variants of naturally occurring innate immune effector molecules known as host defence peptides. IDR peptides were recently demonstrated to limit infection-associated inflammation selectively without compromising host innate immune functions. This study examined the impact of a 12-amino acid IDR peptide, IDR-1002, in pro-inflammatory cytokine interleukin (IL)-1β-induced responses in synovial fibroblasts, a critical cell type in the pathogenesis of inflammatory arthritis.

Methods

Human fibroblast-like synoviocytes (FLS) were stimulated with IL-1β in the presence and absence of IDR-1002. Production of enzyme matrix metalloproteinase-3 (MMP-3) and IL-1-receptor antagonist (IL-1RA) was monitored by enzyme-linked immunosorbent assay (ELISA), and various chemokines were evaluated by using multiplex cytometric bead array. Transcriptional responses were analyzed by quantitative real-time PCR. The impact on IL-1β-induced proteome was investigated by quantitative proteomics by using isobaric tags. IL-1β-induced pathways altered by IDR-1002 implicated by the proteomics analyses were further investigated by using various immunochemical assays. Cellular uptake of the peptide was monitored by using a biotinylated IDR-1002 peptide followed by microscopy probing with streptavidin-Alexa Fluor.

Results

This study demonstrated that IDR-1002 suppressed the production of IL-1β-induced MMP-3 and monocyte chemotactic protein-1 (MCP-1); in contrast, IDR-1002 enhanced the production of IL-1RA, without neutralizing all chemokine responses. IDR-1002 altered the IL-1β-induced proteome primarily by altering the expression of members of nuclear factor kappa-B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways. The proteomics data also suggested that IDR-1002 was altering the transcription factor HNF-4α-mediated responses, known to be critical in metabolic regulation. With various immunochemical assays, it was further demonstrated that IL-1β-induced NF-κB, JNK, and p38 mitogen-activated protein kinase (MAPK) activations were significantly suppressed by IDR-1002.

Conclusions

This study demonstrates the ability of an innate immune-modulatory IDR-peptide to influence the IL-1β-induced regulatory pathways and selectively to suppress inflammatory responses in synovial fibroblasts. The results of this study provide a rationale for examining the use of IDR-peptides as potential therapeutic candidates for chronic inflammatory diseases such as inflammatory arthritis.
Identification of germline alterations of the mad homology 2 domain of SMAD3 and SMAD4 from the Ontario site of the breast cancer family registry (CFR)
Authors: Tram Eric , Ibrahim-zada Irada , Briollais Laurent , Knight Julia A , Andrulis Irene L , Ozcelik Hilmi
Published: August 2011

Introduction

A common feature of neoplastic cells is that mutations in SMADs can contribute to the loss of sensitivity to the anti-tumor effects of transforming growth factor-β (TGF-β). However, germline mutation analysis of SMAD3 and SMAD4, the principle substrates of the TGF-β signaling pathway, has not yet been conducted in breast cancer. Thus, it is currently unknown whether germline SMAD3 and SMAD4 mutations are involved in breast cancer predisposition.

Methods

We performed mutation analysis of the highly conserved mad-homology 2 (MH2) domains for both genes in genomic DNA from 408 non-BRCA1/BRCA2 breast cancer cases and 710 population controls recruited by the Ontario site of the breast cancer family registry (CFR) using denaturing high-performance liquid chromatography (DHPLC) and direct DNA sequencing. The results were interpreted in several ways. First, we adapted nucleotide diversity analysis to quantitatively assess whether the frequency of alterations differ between the two genes. Next, in silico tools were used to predict variants' effect on domain function and mRNA splicing. Finally, 37 cases or controls harboring alterations were tested for aberrant splicing using reverse-transcription polymerase chain reaction (PCR) and real-time PCR statistical comparison of germline expressions by non-parametric Mann-Whitney test of independent samples.

Results

We identified 27 variants including 2 novel SMAD4 coding variants c.1350G > A (p.Gln450Gln), and c.1701A > G (p.Ile525Val). There were no inactivating mutations even though c.1350G > A was predicted to affect exonic splicing enhancers. However, several additional findings were of note: 1) nucleotide diversity estimate for SMAD3 but not SMAD4 indicated that coding variants of the MH2 domain were more infrequent than expected; 2) in breast cancer cases SMAD3 was significantly over-expressed relative to controls (P < 0.05) while the case harboring SMAD4 c.1350G > A was associated with elevated germline expression (> 5-fold); 3) separate analysis using tissue expression data showed statistically significant over-expression of SMAD3 and SMAD4 in breast carcinomas.

Conclusions

This study shows that inactivating germline alterations in SMAD3 and SMAD4 are rare, suggesting a limited role in driving tumorigenesis. Nevertheless, aberrant germline expressions of SMAD3 and SMAD4 may be more common in breast cancer than previously suspected and offer novel insight into their roles in predisposition and/or progression of breast cancer.