bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic morphological changes in the skulls of mice mimicking human Apert syndrome resulting from gain‐of‐function mutation of FGFR2 (P253R)
Authors: Du Xiaolan , Weng Tujun , Sun Qidi , Su Nan , Chen Zhi , Qi Huabing , Jin Ming , Yin Liangjun , He Qifen , Chen Lin 
Published: June 2010

AbstractApert syndrome is caused mainly by gain‐of‐function mutations of fibroblast growth factor receptor 2. We have generated a mouse model (Fgfr2+/P253R) mimicking human Apert syndrome resulting from fibroblast growth factor receptor 2 Pro253Arg mutation using the knock‐in approach. This mouse model in general has the characteristic skull morphology similar to that in humans with Apert syndrome. To characterize the detailed changes of form in the overall skull and its major anatomic structures, euclidean distance matrix analysis was used to quantitatively compare the form and growth difference between the skulls of mutants and their wild‐type controls. There were substantial morphological differences between the skulls of mutants and their controls at 4 and 8 weeks of age (P < 0.01). The mutants showed shortened skull dimensions along the rostrocaudal axis, especially in their face. The width of the frontal bone and the distance between the two orbits were broadened mediolaterally. The neurocrania were significantly increased along the dorsoventral axis and slightly increased along the mediolateral axis, and also had anteriorly displayed opisthion along the rostrocaudal axis. Compared with wild‐type, the mutant mandible had an anteriorly displaced coronoid process and mandibular condyle along the rostrocaudal axis. We further found that there was catch‐up growth in the nasal bone, maxilla, zygomatic bone and some regions of the mandible of the mutant skulls during the 4–8‐week interval. The above‐mentioned findings further validate the Fgfr2+/P253R mouse strain as a good model for human Apert syndrome. The changes in form characterized in this study will help to elucidate the mechanisms through which the Pro253Arg mutation in fibroblast growth factor receptor 2 affects craniofacial development and causes Apert syndrome.
Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T‐cells
Authors: Eastwood D , Findlay L , Poole S , Bird C , Wadhwa M , Moore M , Burns C , Thorpe R , Stebbings R 
Published: June 2010

BACKGROUND AND PURPOSE In 2006, a life‐threatening ‘cytokine storm’, not predicted by pre‐clinical safety testing, rapidly occurred in all six healthy volunteers during the phase I clinical trial of the CD28 superagonist monoclonal antibody (mAb) TGN1412. To date, no unequivocal explanation for the failure of TGN1412 to stimulate profound cytokine release in vitro or in vivo in species used for pre‐clinical safety testing has been established. Here, we have identified a species difference almost certainly responsible for this disparate immunopharmacology.EXPERIMENTAL APPROACH Polychromatic flow cytometry and intracellular cytokine staining were employed to dissect the in vitro immunopharmacology of TGN1412 and other therapeutic mAbs at the cellular level to identify differences between humans and species used for pre‐clinical safety testing.KEY RESULTS In vitro IL‐2 and IFN‐γ release from CD4+ effector memory T‐cells were key indicators of a TGN1412‐type response. This mechanism of cytokine release differed from that of other therapeutic mAbs, which can cause adverse reactions, because these other mAbs stimulate cytokine release primarily from natural killer cells. In contrast to humans, CD28 is not expressed on the CD4+ effector memory T‐cells of all species used for pre‐clinical safety testing, so cannot be stimulated by TGN1412.CONCLUSIONS AND IMPLICATIONS It is likely that activation of CD4+ effector memory T‐cells by TGN1412 was responsible for the cytokine storm. Lack of CD28 expression on the CD4+ effector memory T‐cells of species used for pre‐clinical safety testing of TGN1412 offers an explanation for the failure to predict a ‘cytokine storm’ in humans.
A Novel Subcutaneous Counterpulsation Device: Acute Hemodynamic Efficacy During Pharmacologically Induced Hypertension, Hypotension, and Heart Failure
Authors: Bartoli Carlo R. , Wilson Gregory C. , Giridharan Guruprasad A. , Slaughter Mark S. , Sherwood Leslie C. , Spence Paul A. , Prabhu Sumanth D. , Koenig Steven C. 
Published: June 2010

AbstractThe miniaturization of mechanical assist devices and less invasive implantation techniques may lead to earlier intervention in patients with heart failure. As such, we evaluated the effectiveness of a novel, minimally invasive, implantable counterpulsation device (CPD) in augmenting cardiac function during impaired hemodynamics. We compared the efficacy of a 32‐mL stroke volume CPD with a standard 40‐mL intra‐aortic balloon pump (IABP) over a range of clinically relevant pathophysiological conditions. Male calves were instrumented via thoracotomy, the CPD was anastomosed to the left carotid artery, and the IABP was positioned in the descending aorta. Hemodynamic conditions of hypertension, hypotension, and heart failure were pharmacologically simulated and data were recorded during CPD and IABP support (off, 1:2, 1:1 modes) for each condition. In all three pathophysiological conditions, the CPD and IABP produced similar and statistically significant (P < 0.05) increases in coronary artery blood flow normalized to the left ventricular (LV) workload. During hypotension and heart failure conditions, however, the CPD produced significantly greater reductions in LV workload and myocardial oxygen consumption as compared with the IABP. A novel 32‐mL CPD connected to a peripheral artery produced equivalent or greater hemodynamic benefits than a standard 40‐mL IABP during pharmacologically induced hypertension, hypotension, and heart failure conditions.
Genetic research in the blood bank: acceptability to Northern California donors
Authors: Rice Megan S. , Custer Brian S. , Hindes Daniel A. , Hirschler Nora V. , Nguyen Kim‐Anh , Busch Michael P. , Murphy Edward L. 
Published: June 2010

BACKGROUND: Blood banks have large altruistic donor populations and existing infrastructure that make them attractive sites for genetic epidemiologic research, but donors' willingness to participate and the impact on blood donation are unknown.STUDY DESIGN AND METHODS: A total of 2162 blood donors in Northern California responded to a cross‐sectional questionnaire in August and September 2007. Participants were asked their likelihood of participation and future blood donation under three different scenarios: identity‐linked genetic research, identity‐unlinked genetic research, and genetic testing as a service.RESULTS: The majority of blood donors indicated that they would be likely or very likely to participate in identity‐linked genetic research (67%) and in identity‐unlinked genetic research (54%). While older donors and more frequent donors were more likely to participate in identity‐linked research, younger, Caucasian, more educated, and more frequent donors were more likely to participate in identity‐unlinked research. Less than 10% of donors indicated they would be less likely to donate blood in the future if genetic research was conducted at blood banks. More than 75% of donors would be interested in genetic testing as an optional service at the blood bank, but more than 20% of donors would be less likely to donate if such a service was offered.CONCLUSION: Overall, we found that the majority of blood donors would be likely to participate in genetic research and that less than 10% would be less inclined to donate if such research was conducted by blood banks.
Sonication of Explanted Cardiac Rhythm Management Devices for the Diagnosis of Pocket Infections and Asymptomatic Bacterial Colonization
Authors: MASON PAMELA K. , DIMARCO JOHN P. , FERGUSON JOHN D. , MAHAPATRA SRIJOY , MANGRUM J. MICHAEL , BILCHICK KENNETH C. , MOORMAN J. RANDALL , LAKE DOUGLAS E. , BERGIN JAMES D. 
Published: June 2010

Background: Correct diagnosis of the causative organism is critical for the treatment of pacemaker and defibrillator pocket infections. No gold standard for this exists, although swab and tissue cultures are frequently used. The purpose of this study was to determine the value of ultrasonication of explanted generators in the diagnosis of pocket infections and asymptomatic bacterial colonization.
Methods: Samples were prospectively collected during pacemaker and defibrillator generator extractions for elective replacements, upgrades, or pocket infections. The devices were placed in an ultrasonicator for 5 minutes and the fluid sent for culture, along with swab and tissue cultures.
Results: Eighty‐two patients with pacemakers (n = 46) or defibrillators (n = 36) underwent generator explantation, 66 of these for elective reasons and 16 for pocket infection. In patients with pocket infection, 15 (94%) received a definitive bacterial diagnosis using a combination of all three‐culture modalities. Cultures were positive in 15 sonicated fluid, 13 tissue, and 11 swab samples, with Staphylococcus aureus and other skin flora commonly seen. In asymptomatic patients, 14 (21%) had positive cultures. Cultures were positive in 11 sonicated fluid, eight tissue, and two swab samples. Skin flora was commonly seen, but three of the sonicated fluid cultures grew gram‐negative rods. No patients with asymptomatic colonization developed clinical infection during the follow‐up period.
Conclusions: Ultrasonication is an inexpensive and simple technique that improves the bacteriologic diagnosis of device pocket infections. It also identifies a significant proportion of patients with asymptomatic colonization, although this is not a marker of future pocket infection. (PACE 2011; 34:143–149)
Programming Antitachycardia Pacing for Primary Prevention in Patients With Implantable Cardioverter Defibrillators: Results From the PROVE Trial
Authors: SAEED MOHAMMAD , NEASON CURTIS G. , RAZAVI MEHDI , CHANDIRAMANI SHANKER , ALONSO JOSEPH , NATARAJAN SENTHIL , IP JOHN H. , PERESS DARREN F. , RAMADAS SUMATI , MASSUMI ALI 
Published: June 2010

Programming ATP for ICD Patients. Objectives: The PROVE trial was designed to determine if antitachycardia pacing (ATP) is clinically beneficial for primary prevention in patients who have implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT‐Ds). Background: Use of ICDs and CRT‐Ds reduces mortality in patients with ventricular dysfunction and mild to moderate heart failure. However, in studies of the primary prevention population, shock‐only ICDs are predominantly used, without ATP programming for less painful termination of ventricular tachycardia (VT). Methods: We conducted a prospective, nonrandomized, multicenter study using market‐released ICDs and CRT‐Ds. Patients received devices programmed to deliver ATP for VT cycle lengths of 270–330 ms. Follow‐up evaluation was performed at 3, 6, and 12 months. The incidence of VT and the rate of successful termination by ATP were analyzed. Results: Of 830 patients in the study population (men, 73%; mean age, 67.3 ± 12 years), 32% received single‐chamber ICDs, 44% dual‐chamber ICDs, and 24% CRT‐Ds. ATP was attempted for 112 VT episodes in 71 patients, and 103 (92%) of the VT episodes were successfully terminated. Three VT episodes were accelerated by ATP and required termination by ICD shock; 6 episodes terminated spontaneously or by ICD shock. Conclusions: VT is common in patients without a history of this arrhythmia who have received ICDs or CRT‐Ds for primary prevention indications. Programming ICDs for ATP therapy at the time of implantation could potentially terminate most VT episodes and reduce the number of painful shocks for these patients. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1349‐1354, December 2010)
Initial Experience With a Multielectrode Catheter Equipped With the Single‐Axis Sensor Technology for High‐Density Electroanatomical Mapping in a Swine Model
Authors: BEINART ROY , PERNA FRANCESCO , DANIK STEPHAN , BARRETT CONOR D. , HEIST E. KEVIN , RUSKIN JEREMY , MANSOUR MOUSSA 
Published: June 2010

Utility of Single‐Axis Sensor Technology in High‐Density Electroanatomical Mapping. Introduction: Magnetic‐based electroanatomical mapping systems are widely used during catheter ablation. Currently, the size of the sensor incorporated in the catheter to allow its localization is large, prohibiting the placement of more than one sensor on any single catheter. As a result, multielectrode catheters cannot be tracked by the magnetic‐based mapping systems. Single‐axis sensors (SAS) are new generation sensors that are significantly smaller in size. The small size of these new sensors allows the placement of more than one sensor on each catheter, allowing the tracking of multielectrode catheters. The objective of this study is to test the feasibility of creating high‐density magnetic electroanatomical maps using a new generation multielectrode catheter equipped with the SAS technology. Methods and Results: Anatomical reconstruction of cardiac chambers and the aorta, together with activation mapping of the right atrium during both sinus rhythm and pacing‐induced premature atrial contractions (PACs), were performed in 5 swine using both a conventional mapping catheter and the novel multielectrode catheter equipped with SAS. The multielectrode mapping provided a detailed definition of cardiac anatomy while requiring shorter acquisition times. In addition, mapping of PACs origin was significantly faster using the multielectrode catheter. Conclusion: The novel multielectrode catheter equipped with the SAS technology can be used in combination with magnetic electroanatomical mapping systems to generate high‐density anatomical reconstructions and activation maps. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1403‐1407, December 2010)
Rectourethral fistula after radical prostatectomy: Transperineal repair in jack‐knife position
Authors: Ho Brian , Ho Kwan‐Lun , Tsu James Hok‐Leung , Ng Raymond Wai‐Man , Law Wai‐Lun , Tam Po‐Chor 
Published: June 2010

Background:  Rectourethral fistula is a rare complication of radical prostatectomy. Risk factors include history of pelvic irradiation, cryotherapy, intraoperative rectal injury or transurethral resection of the prostate. Diagnosis of rectourethral fistula requires a high index of suspicion, and complete work‐up with endoscopy and imaging studies. The majority of patients require operative intervention, with approaches ranging from transabdominal, transrectal, transanal, and transperineal routes.Method:  We report two patients with rectourethral fistula after radical prostatectomy. The first patient was a 59‐year‐old man who underwent an uncomplicated laparoscopic radical prostatectomy for early prostate cancer in another hospital. The second patient was a 64‐year‐old man who had local recurrence after cryotherapy for prostate cancer. He underwent salvage radical prostatectomy in a private hospital, which was complicated by intraoperative rectal injury.Results:  In both patients, the rectourethral fistulae were successfully repaired with a transperineal approach in the prone jack‐knife position.Conclusion:  We found that the transperineal approach in the prone jack‐knife position offered excellent exposure, allowed versatile surgical manoeuvres and produced successful repair with good continence outcomes.
Retrospective review of the outcome of post‐chemotherapy retroperitoneal lymph node dissection in the management of metastatic testicular cancer: Local experience
Authors: Chung Vera Y. , Yee Chi‐Hang , Hou See‐Ming , Yip Sidney K.H. , Ng Chi‐Fai 
Published: June 2010

Objective:  Post‐chemotherapy retroperitoneal lymph node dissection (RPLND) for metastatic testicular cancer is an uncommon surgical procedure in Hong Kong. Therefore, in the present article, we review the perioperative and long‐term morbidity, as well as the survival outcome for RPLND carried out in a urological centre.Method:  This is a retrospective study of patients suffering from metastatic testicular cancer with post‐chemotherapy residual mass subjected to RPLND between 1998 and 2008. Patient and tumour parameters including initial presentation, chemotherapy regimens received prior to RPLND, perioperative outcomes, pathology and long‐term results were retrieved from hospital notes and reviewed.Results:  Seven patients who underwent post‐chemotherapy RPLND were included in the present review. The mean follow‐up time was 63.7 months (range 6–136 months), and no recurrence or mortality was reported in this series. Early perioperative morbidity included pulmonary oedema (one), chylous ascites (one) and wound dehiscence (one). Other than ejaculatory dysfunction in all of the patients, there was no major‐long term complication reported in our series.Conclusion:  This local series confirmed the survival benefit and association of minimal long‐term morbidity with post‐chemotherapy RPLND.
How do Plant Morphological Characteristics, Species Composition and Richness Regulate Eco‐hydrological Function?
Authors: Wang Zhen‐Hong , Duan Chang‐Qun 
Published: June 2010

Abstract Although considerable research has focused on the relationship between ecosystem structure and function, interactions of plant morphological characteristics, species composition and richness with eco‐hydrological functions remain unclear. We measured water adherence (i.e. the capacity of a plant species to retain water), documented plant surface morphology and observed surface runoff at three sites in China. The adhering water ratios for each plant species differed, ranging from 17.1% to 151.5% in leaves, and from 14.4% to 41.1% in branches. Small, light‐weight, soft, non‐cuticularized leaves that were densely situated on small branches showed good water adherence. The next best adherence was found by branches with intermediately coarse surfaces. The plant species with high standing biomass also showed good water adherence, and the contribution of a species to total adherence was dependent upon its aboveground standing biomass. Vegetation parameters strongly affected water adherence, whereas the effect of species richness was not significant. Conversely, species richness showed a significant influence on surface runoff. The effect of plant morphological characteristics and composition constitutes a basic process in the regulation of eco‐hydrological function, and vegetation parameters play somewhat different roles in that regulation. The key roles must therefore be considered from a management perspective.
Donor hemovigilance: safety as the first priority of blood donor management
Authors: Benjamin R. J. 
Published: June 2010

Background  The American Red Cross instituted a donor hemovigilance program (HVP) in its 35 regional blood centres in 2003 to document adverse events occurring at the time of donation or reported later. The aims are to describe and quantitate rare events using standard definitions, define risk factors, design specific interventions and to assess outcomes. In the 1990s, most US blood centres converted to 500 ml whole blood (WB) collection bags to maximize blood collection. The AABB (formerly known as the American Association of Blood Banks) instituted a standard (#5.4.1.A) to permit a maximum blood loss of 10·5 ml/kg and minimum donor weight of 50 kg (110 lb), allowing 525 ml of blood to be removed from the smallest donors. In the last decade, the majority of States have enacted legislation to allow 16‐year‐old donors to donate with parental consent.Methods  Standardized adverse event definitions and reporting were instituted in 2003, and adverse event data were collated and analysed at the National Medical Office. Standard database and statistical analytical methods were utilized. Estimated blood volume was calculated based on height, weight and gender, using the method of Nadler et al. Surgery 1962; 51:224–231.Results  Analysis of HVP data from 2002 to 2006 highlighted that young, first time, female donors were at risk for vasovagal reactions, injuries related to falls and the need for outside medical care. Multivariate analysis revealed young age, low estimated blood volume (<3·5 l) (EBV) and first‐time donation status as major independent risk factors. Calculation of EBV revealed that current AABB standards allow, and CFR limits do not prevent, 15–20% blood loss of EBV from short, low‐weight female donors.Interventions to reduce vasovagal reactions were piloted, starting in 2008, including: (i) a controlled environment through standardized work guidance, physical setup and staffing matrices; (ii) improved donor and parent educational material prior to donation; (iii) enhanced donor monitoring post donation; (iv) fluid intake encouraged within 30 minutes of donation; (v) distraction and muscle tension techniques; (vi) use of apheresis double red cell collection in eligible donors; (vii) enhanced post donation instructions to donors and patients; (viii) implementation of selective height and weight restrictions in donors <19 years old to avoid collection from donors with EBV <3·5 l.Conclusions  A national HVP has highlighted the issue of vasovagal syncope‐like reactions in young first‐time donors with low EBV leading to multiple interventions designed to reduce risk. Outcomes are being assessed and monitored. Current AABB standards do not adequately protect young donors with low height/weight from excess blood loss in the United States.