bluuebunny/crossref_metadata_2025 huggingface dataset:
Conivaptan increases serum sodium in hyponatremic patients with end-stage liver disease
Authors: O'Leary Jacqueline G. , Davis Gary L.
Published: September 2009

Hyponatremia is associated with increased mortality in patients with end-stage liver disease and a greater risk of perioperative mortality with liver transplantation. We performed a retrospective review of our experience with conivaptan as a means of acutely increasing serum sodium in end-stage liver disease patients. The primary group consisted of 15 patients with end-stage liver disease who remained hyponatremic despite discontinuation of diuretics and a 1-L fluid restriction. Twenty milligrams of conivaptan was intravenously administered over 30 minutes, and this was followed by an infusion of 20 mg over 24 hours for 1 to 4 days. A second group of 9 hyponatremic end-stage liver disease patients was treated with 1-L fluid restriction and conivaptan while remaining on diuretics. In the group without diuretics, the mean serum sodium was 124 mmol/L 1 day before and on the day of conivaptan initiation, but the serum sodium rose to a mean of 127.7 mmol/L by day 1 and further increased to 128.6 mmol/L by the second day of the infusion. Despite the continuation of diuretics, the second group of 9 patients also had an increase in serum sodium from the day of conivaptan initiation (125.7 mmol/L) to 2 days after the treatment (130.6 mmol/L). Eleven patients underwent successful liver transplantation, 2 remained on the list for transplantation, and 11 were not candidates for transplantation and either died (7) or were discharged home and lost to follow-up (4). In conclusion, a short course of conivaptan increases serum sodium in patients with end-stage liver disease and may reduce the risk of proceeding to liver transplantation. Further study in a prospective clinical trial is needed to confirm safety and efficacy. Liver Transpl 15:1325–1329, 2009. © 2009 AASLD.
Liver grafts from donors with central nervous system tumors: A single-center perspective
Authors: Kashyap Randeep , Ryan Charlotte , Sharma Rajeev , Maloo Manoj K. , Safadjou Saman , Graham Maureen , Tretheway David , Jain Ashokkumar , Orloff Mark
Published: September 2009

Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 ± 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 ± 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality. Liver Transpl 15:1204–1208, 2009. © 2009 AASLD.
Predicting recurrence after liver transplantation in patients with hepatocellular carcinoma exceeding the up-to-seven criteria
Authors: D'Amico Francesco , Schwartz Myron , Vitale Alessandro , Tabrizian Parissa , Roayaie Sasan , Thung Swan , Guido Maria , del Rio Martin Juan , Schiano Thomas , Cillo Umberto
Published: September 2009

The up-to-seven (Up-to-7) criteria [with 7 being the sum of the size and number of tumors for any given hepatocellular carcinoma (HCC)] have been recently proposed to identify potential candidates for liver transplantation (LT) among patients exceeding the Milan criteria. The aim of this study was to compare the ability of the available pathologic staging systems (the Milan, University of California San Francisco, and Up-to-7 criteria) to predict recurrence. A study population of 479 HCC transplanted patients was identified from prospectively collected databases at Mount Sinai Medical Center (New York, NY) and the University of Padua (Padua, Italy). The best pathologic staging system was identified with log rank, proportion separation index (PSEP), and Cox analyses. Pathologic tumor characteristics (tumor number, tumor size, sum of diameters, macroscopic and microscopic vascular invasion, and grading) were then tested by univariate and multivariate Cox analyses in the prognostic subgroups within and beyond the calculated criteria. The Up-to-7 criteria performed as the best pathologic staging system, the calculated 1-, 3-, and 5-year recurrence probabilities being 4%, 8%, and 14% within the criteria (n = 355) and 22%, 45%, 51% beyond the criteria (n = 124; P < 0.0001) and the calculated PSEP being 0.27 (95% confidence interval = 0.23-0.31). In multivariate analysis, only biological variables (vascular invasion and tumor grade) significantly predicted recurrence beyond the Up-to-7 criteria. A 3-stage pathologic staging system with a potential to be applied in the preoperative setting was thus created: within the Up-to-7 criteria (recurrence rate = 8%), beyond the Up-to-7 criteria without macrovascular invasion and poorly differentiated grade (recurrence rate = 24%), and beyond the Up-to-7 criteria with macrovascular invasion and/or poorly differentiated grade (recurrence rate = 45%). In conclusion, HCC patients within the pathologic Up-to-7 criteria were associated with a low risk of recurrence after LT. Beyond these criteria, however, a significant proportion of patients with a good HCC biological profile had an acceptable risk of recurrence. Liver Transpl 15:1278–1287, 2009. © 2009 AASLD.
Determining temperature lapse rates over mountain slopes using vertically weighted regression: a case study from the Pyrenees
Authors: Pagès Meritxell , Miró Josep Ramon
Published: September 2009

This study took place in the Pyrenees Range, in the northeastern Iberian Peninsula. The Pyrenees extend longitudinally, separating the Iberian Peninsula from the rest of Europe, and high peaks around 3000 m arise from deep valleys. As a mountain range it creates a barrier to advection, in this case from the north and south, and typical meteorological phenomena of mountainous areas occur within it (inversions, Foehn effect, extreme wind‐chill, snow storms). Thus, two specific valleys in Catalonia were considered, Val d'Aran and Cerdanya. In both valleys automatic weather stations (AWSs) are available at similar heights. Although these valleys are only 100 km apart, they have different climates. However, the main reason for developing the study was that Numerical Weather Prediction (NWP) has problems when forecasting temperatures in complex terrain areas, mainly in the valley floor in winter season.

Firstly, different equations based on a multilinear regression were obtained for each weather station. Multilinear regression was considered in this case as the most suitable downscaling method and data used were provided by the AWSs and MM5 (PSU/NCAR mesoscale model) numerical weather prediction model outputs.

These equations were obtained to set up a Geographically Weighted Regression (GWR) method, although this one was modified and changed to a Vertically Weighted Regression (VWR) in order to create vertical temperature profiles. Copyright © 2009 Royal Meteorological Society
Power spectral analysis of perfusion signals on free radial forearm flap transplantation in humans
Authors: Sun Tzong‐Bor , Kuo Terry B. J. , Yang Cheryl C. H.
Published: September 2009

Forearm cutaneous perfusion is an established in vivo model in many clinical and basic researches to explore the peripheral circulation. The aim of our study is to characterize the dynamic properties of regional microcirculation after simultaneous denervation and revascularization in free forearm flap transplantations. Serial changes in laser Doppler flow and cutaneous temperature were measured during 14 forearm flap transplantations. Digitalized perfusion data were relayed for power spectral analysis based on the fast Fourier transform. Real time heart rate variability was measured to verify the influence of systemic autonomic nervous modulations. The basal flow expressed a threefold to fourfold increase, from 20.31 ± 3.25 to 73.79 ± 11.78 PU, after the transplantation. Frequency domain analysis of cutaneous blood flow variability showed significantly increased high frequency (0.15–0.4 Hz, 55.14% ± 3.31% to 65.31% ± 2.78%, P = 0.0035) and decreased very low frequency (0.003–0.04 Hz, 18.61% ± 2.70% to 9.25% ± 1.38%, P = 0.0049) power fraction after flap transfer. Simultaneous denervation and revascularization of forearm flaps increased the regional blood flow significantly that was caused by increased high frequency and decreased very low frequency fractional contributions in dynamic regulation of regional cutaneous microcirculation. They are associated with the sympathetic denervation and reactive hyperemia, respectively. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.
Management strategies following microsurgical flap failure
Authors: Lineaweaver William , Akdemir Ovunc , Schleich Arno
Published: September 2009

Although increasingly rare, failed microsurgical flaps are a complicated clinical problem when they occur. Review of reports of management following microsurgical flap failure offers an outline of options. A substantial number of breast and extremity patients elect abandonment of reconstruction. The majority of head and neck, breast, and extremity patients proceed to nonmicrosurgical reconstructive options. Head and neck patients (38%) and 35% of extremity patients elect to have second microsurgical flaps, and 84% of these procedures were successful.Patient management following microsurgical flap failure includes strategic abandonment of reconstruction in some cases, use of conventional procedures in a majority of cases, and further microsurgical procedures in one‐third of cases. The reconstructive surgeon should have this range of possibilities available for these difficult cases. © 2009 Wiley‐Liss, Inc. Microsurgery, 2010.
Reversed flow lateral circumflex femoral vessels as recipients for free fibular grafting in treatment of femoral head osteonecrosis
Authors: Lowrie A. G. , Rao K. , Nanu A. , Erdmann M. W. H.
Published: September 2009

Free fibular bone grafting is an effective treatment for early osteonecrosis of the femoral head in young patients. However, recipient vessels are often small rendering microvascular anastomosis difficult. We have developed a novel technique using retrograde flow through the branches of the lateral circumflex femoral artery to use the proximal end of the artery as the recipient vessel. A vessel diameter of up to 5 mm is obtained providing a good match with the peroneal vessels. We used this technique to perform vascularized bone grafting of the femoral head in 10 patients with Ficat grade 2 and 3 osteonecrosis. Pulsatile retrograde flow from the lateral circumflex femoral artery was observed in each case. Retrospective review gave a median follow up of 52 months (range 17–99). Symptoms improved in all 10 cases. There was no radiological deterioration over the period of follow‐up in eight cases. One patient underwent conversion to a total hip replacement 24 months after surgery. These results compare favorably with other studies. The lateral circumflex femoral artery turnover technique is a reliable and useful technique in vascularized bone grafting of the femoral head. © 2009 Wiley‐Liss, Inc. Microsurgery, 2010.
Surgical decompression for notalgia paresthetica: A case report
Authors: Williams Eric H. , Rosson Gedge D. , Elsamanoudi Ibrahim , Dellon A. Lee
Published: September 2009

Notalgia paresthetica is a rare nerve compression. From the Greek word noton, meaning “back,” and algia, meaning “pain,” “notalgia paresthetica” implies that symptoms of burning pain, itching, and/or numbness in the localized region between the spinous processes of T2 through T6 and the medial border of the scapula constitute a nerve compression syndrome. The compressed nerve is the dorsal branch of the spinal nerve. It is compressed by the paraspinous muscles and fascia against the transverse process of these spinal segments. This is the first report of symptomatic relief by decompression of this nerve. © 2009 Wiley‐Liss, Inc. Microsurgery, 2010.
Upper extremity reconstruction using free SCIA/SIEA flap
Authors: Nasir Serdar , Aydin Mustafa Asim
Published: September 2009

The most suitable free flap alternative in upper extremity reconstruction has adequate and quality of tissue with consistent vascular pedicle. Free flap must provide convenient tissue texture to reconstruct aesthetic and functional units of upper extremity. Furthermore, minimal donor site morbidity is preferred features in free flap election. In our efforts to obtain the best possible outcome for patients, we chose, as a first priority, the free superficial circumflex inferior artery (SCIA)/superficial inferior epigastric artery (SIEA) flap over other free flap options for the soft‐tissue reconstruction of upper extremities. The authors retrospectively report the results of 20 free SCIA/SIEA flaps for upper extremity reconstruction during the past 3 years. Nineteen of 20 flaps were successful (95%): three required emergent postoperative reexploration of the anastomosis and one failed. Flap thinning (n = 4) was performed during the flap harvest, whereas some flaps were thinned with secondary debulking (n = 4). The functional and aesthetic results were evaluated as acceptable by all patients. Based on our results, a free SCIA/SIEA flap has the following advantages in soft‐tissue reconstruction of the upper extremity: (1) if necessary, flap thinning may be performed safely at the time of flap elevation and (2) flaps are harvested using a lower abdominal incision so that it causes minimal donor site scar. © 2009 Wiley‐Liss, Inc. Microsurgery, 2010.
The efficacy of postoperative monitoring: A single surgeon comparison of clinical monitoring and the implantable Doppler probe in 547 consecutive free flaps
Authors: Rozen Warren M. , Chubb Daniel , Whitaker Iain S. , Acosta Rafael
Published: September 2009

Background: An important element in achieving high success rates with free flap surgery has been the use of different techniques for monitoring flaps postoperatively as a means to detecting vascular compromise. Successful monitoring of the vascular pedicle to a flap can potentiate rapid return to theater in the setting of compromise, with the potential to salvage the flap. There is little evidence that any technique offers any advantage over clinical monitoring alone. Methods: A consecutive series of 547 patients from a single plastic surgical unit who underwent a fasciocutaneous free flap operation for breast reconstruction [deep inferior epigastric artery perforator (DIEP) flap, superficial inferior epigastric artery (SIEA) flap, or superior gluteal artery perforator (SGAP) flap] were included. A comparison was made between the first 426 consecutive patients in whom flap monitoring was performed using clinical monitoring alone and the subsequent 121 patients in whom monitoring was achieved with the Cook‐Swartz implantable Doppler probe. Outcome measures included flap salvage rate and false‐positive rate. Results: There was a strong trend toward improved salvage rates with the implantable Doppler probe compared with clinical monitoring (80% vs. 66%, P = 0.48). When combined with the literature (meta‐analysis), the data prove statistically significant (P < 0.01). There was no statistical difference between the groups for false‐positive rates. Conclusion: Flap monitoring with the implantable Doppler probe can improve flap salvage rates without increasing the rate of false‐positive takebacks. © 2009 Wiley‐Liss, Inc. Microsurgery, 2010.
The correlation between calcium absorption and electrophysiological recovery in crushed rat peripheral nerves
Authors: Yan Ji‐Geng , Matloub Hani S. , Yan Yuhui , Agresti Michael , Zhang Lin‐Ling , Jaradeh Safwan S.
Published: September 2009

The correlation between calcium ion (Ca2+) concentration and electrophysiological recovery in crushed peripheral nerves has not been studied. Observing and quantifying the Ca2+intensity in live normal and crushed peripheral nerves was performed using a novel microfine tearing technique and Calcium Green‐1 Acetoxymethyl ester stain, a fluorescent Ca2+indicator. Ca2+was shown to be homogeneously distributed in the myelinated sheaths. After a crush injury, there was significant stasis in the injured zone and the portion distal to the injury. The Ca2+has been almost completely absorbed after 24 weeks in the injured nerve to be similar to the controls. The process of the calcium absorption was correlated with the Compound Muscle Action Potential recovery process of the injured nerves. This correlation was statistically significant (r= −0.81,P< 0.05). The better understanding of this process will help us to improve nerve regeneration after peripheral nerve injury. © 2009 Wiley‐Liss, Inc. Microsurgery, 2010.
A subfascial variant of the deep inferior epigastric artery demonstrated by preoperative multidetector computed tomographic angiography: A case report
Authors: Garusi Cristina , Lohsiriwat Visnu , de Lorenzi Francesca , Manconi Andrea , de Fiori Elvio , Bellomi Massimo
Published: September 2009

Precise preoperative imaging by multidetector computed tomographic (MDCT) angiography for planning of deep inferior epigastric artery perforator (DIEP) flap dissection has been reported for enormous advantages in terms of reduced operative time and minimized flap‐related complications. This case report shows a particularly rare anatomical subfascia variant of deep inferior epigastric artery (DIEA) which can be preoperatively demonstrated by MDCT angiogram. Therefore, the intraoperative finding also confirms the radiologic data and results in meticulous flap harvesting during incision on anterior rectus sheath. Additionally, the authors emphasize on performing preoperative high quality imaging for DIEP intervention precisely for specific vulnerable course of subfascial plane DIEP, which is rare but tends to be at risk without foreknowing its exact course. © 2009 Wiley‐Liss, Inc. Microsurgery, 2010.
A single center comparison of one versus two venous anastomoses in 564 consecutive DIEP flaps: Investigating the effect on venous congestion and flap survival
Authors: Enajat Morteza , Rozen Warren M. , Whitaker Iain S. , Smit Jeroen M. , Acosta Rafael
Published: September 2009

Background: Venous complications have been reported as the more frequently encountered vascular complications seen in the transfer of deep inferior epigastric artery (DIEA) perforator (DIEP) flaps, with a variety of techniques described for augmenting the venous drainage of these flaps to minimize venous congestion. The benefits of such techniques have not been shown to be of clinical benefit on a large scale due to the small number of cases in published series. Methods: A retrospective study of 564 consecutive DIEP flaps at a single institution was undertaken, comparing the prospective use of one venous anastomosis (273 cases) to two anastomoses (291 cases). The secondary donor vein comprised a second DIEA venae commitante in 7.9% of cases and a superficial inferior epigastric vein (SIEV) in 92.1%. Clinical outcomes were assessed, in particular rates of venous congestion. Results: The use of two venous anastomoses resulted in a significant reduction in the number of cases of venous congestion to zero (0 vs. 7, P = 0.006). All other outcomes were similar between groups. Notably, the use of a secondary vein did not result in any significant increase in operative time (385 minutes vs. 383 minutes, P = 0.57). Conclusions: The use of a secondary vein in the drainage of a DIEP flap can significantly reduce the incidence of venous congestion, with no detriment to complication rates. Consideration of incorporating both the superficial and deep venous systems is an approach that may further improve the venous drainage of the flap. © 2009 Wiley‐Liss, Inc. Microsurgery, 2010.
Fast targeted multidimensional NMR metabolomics of colorectal cancer
Authors: Ludwig C. , Ward D. G. , Martin A. , Viant M. R. , Ismail T. , Johnson P. J. , Wakelam M. J. O. , Günther U. L.
Published: September 2009

The study of small molecules in body fluids has become an important tool to monitor the state of biological organisms. Applications range from model studies using cell lines to applications where human body fluids are used to monitor disease states or drug responses. NMR spectroscopy has been an important tool for metabolomics although severe overlap of signals has limited the number of compounds, which can be unambiguously identified and quantified. Therefore, deconvolution of NMR spectra is one of the greatest challenges for NMR‐based metabolomics. This has commonly been achieved by using multidimensional spectra that have the disadvantage of requiring significantly longer acquisition times. Recently, a number of methods have been described to record NMR spectra much faster. Here, we explore the use of Hadamard‐encoded TOCSY spectra to simultaneously select multiple lines from crowded NMR spectra of blood serum samples to acquire pseudo‐two‐dimensional spectra in minutes which would otherwise require many hours. The potential of this approach is demonstrated for the detection of a signature for colorectal cancer from human blood samples. Copyright © 2009 John Wiley & Sons, Ltd.
The molecular machinery of germ line specification
Authors: Ewen‐Campen Ben , Schwager Evelyn E. , Extavour Cassandra G.M.
Published: September 2009

Germ cells occupy a unique position in animal reproduction, development, and evolution. In sexually reproducing animals, only they can produce gametes and contribute genetically to subsequent generations. Nonetheless, germ line specification during embryogenesis is conceptually the same as the specification of any somatic cell type: germ cells must activate a specific gene regulatory network in order to differentiate and go through gametogenesis. While many genes with critical roles in the germ line have been characterized with respect to expression pattern and genetic interactions, it is the molecular interactions of the relevant gene products that are ultimately responsible for germ cell differentiation. This review summarizes the current state of knowledge on the molecular functions and biochemical connections between germ line gene products. We find that homologous genes often interact physically with the same conserved molecular partners across the metazoans. We also point out cases of nonhomologous genes from different species whose gene products play analogous biological roles in the germ line. We suggest a preliminary molecular definition of an ancestral “pluripotency module” that could have been modified during metazoan evolution to become specific to the germ line. Mol. Reprod. Dev. 77: 3–18, 2010. © 2009 Wiley‐Liss, Inc.
Neuronal and glial cerebrospinal fluid protein biomarkers are elevated after West Nile Virus infection
Authors: Petzold A. , Groves M. , Leis A.A. , Scaravilli F. , Stokic D.S.
Published: September 2009

Neurotrophic West Nile virus (WNV) disease is a severe arbovirus infection in which neuronal loss is the likely anatomical substrate for the high morbidity and mortality. We investigated whether cerebrospinal fluid (CSF) protein biomarkers were elevated in vivo and related to disease severity in patients with WNV infection. This exploratory study included 114 patients (24 acute WNV, 77 noninflammatory controls, six peripheral neuropathies, seven aseptic meningoencephalitis). CSF levels of neuronal (neurofilaments, NfH‐SMI35) and glial (glial fibrillary acidic protein, GFAP, S100B) biomarkers were measured by enzyme‐linked immunosorbent assay (ELISA). Immunocytochemistry was performed in two fatal WNV cases. A significant proportion of patients with WNV had pathological CSF levels for NfH‐SMI35 (58%, median concentration 1.01 ng/mL), GFAP (58%, 10 pg/mL), and S100B (90%, 1.29 ng/mL). The results were consistent with postmortem evidence for neuronal death and astrogliosis. Surprisingly, CSF protein biomarker levels were also found to be pathological in a considerable proportion of patients who presented with WNV fever only (100% for GFAP and S100B and 43% for NfH‐SMI35). Elevated CSF protein biomarker levels are suggestive of neuronal death and glial pathology in human WNV infection. The results indicate the presence of neuroinvasive disease across the spectrum of WNV disease, including WNV fever. Muscle Nerve, 2010
Role of gelatinases in disuse‐induced skeletal muscle atrophy
Authors: Liu Xuhui , Lee David J. , Skittone Laura K. , Natsuhara Kyle , Kim Hubert T.
Published: September 2009

Gelatinases are a subgroup of the family of matrix metalloproteinases, which contains two members—gelatinase A and B. These enzymes play an important role in basement membrane homeostasis. Previous studies have associated basement membrane degradation with skeletal muscle atrophy. However, the specific contribution of gelatinases to the pathobiology of muscle atrophy remains unknown. In this study we examined the specific roles of gelatinase A and B in disuse‐induced skeletal muscle atrophy using knockout mice. Although both gelatinase A and B are highly upregulated in disused muscle, only gelatinase A null mice had significantly reduced muscle atrophy as compared to wildtype littermates. Type IV collagen and laminin, two major components of basement membrane, were relatively well‐preserved in disused muscle in gelatinase A null mice, but not in gelatinase B null mice. These findings suggest that gelatinase A, and not gelatinase B, plays a critical role in disuse‐induced skeletal muscle atrophy. Muscle Nerve, 2010
The effects of welfare reform on the academic performance of children in low‐income households
Authors: Miller Amalia R. , Zhang Lei
Published: September 2009

During the 1990s, U.S. welfare policy underwent dramatic reforms aimed at promoting employment and reducing dependence. Although the immediate effects on adult labor supply and family income have been studied extensively, this paper is the first to evaluate the long‐run effects on children's well‐being. Using a decade of national math achievement data and controlling for contemporaneous changes in education policy and environment, we associate welfare reform with relative test score improvements for low‐income students. Greater gains occur in states with larger initial welfare caseloads and larger caseload reductions.© 2009 by the Association for Public Policy Analysis and Management.
Voter‐weighted environmental preferences
Authors: Bell Jason , Huber Joel , Viscusi W. Kip
Published: September 2009

This article examines the political economy of preferences with respect to the environment using a new stated preference survey that presents the first benefit values for national water quality levels. The mean valuation greatly exceeds the median value, as the distribution of valuations is highly skewed. The study couples the survey valuations with unique and extensive information on respondent voting patterns. Preferences of registered voters are similar to the preferences of the population at large, but median voters value water quality more than nonvoters. The strongest contrast related to voter‐weighted preferences is among voters for different candidates, as those who voted for Gore in the 2000 presidential election have the highest environmental values. © 2009 by the Association for Public Policy Analysis and Management.
Collusion in auctions for emission permits: An experimental analysis
Authors: Burtraw Dallas , Goeree Jacob , Holt Charles A. , Myers Erica , Palmer Karen , Shobe William
Published: September 2009

Environmental markets have several institutional features that provide a new context for the use of auctions and that have not been studied previously. This paper reports on laboratory experiments testing three auction forms—uniform and discriminatory price sealed‐bid auctions and an ascending clock auction. We test the ability of subjects to tacitly or explicitly collude in order to maximize profits. Our main result is that the discriminatory and uniform price auctions produce greater revenues than the clock auction, both with and without explicit communication. The clock appears to facilitate successful collusion, both because of its sequential structure and because it allows bidders to focus on one dimension of cooperation (quantity) rather than two (price and quantity).© 2009 by the Association for Public Policy Analysis and Management.
Phenomenon of phase inversion in high impact polystyrene: Physico‐chemical, rheological and morphological study in the presence of chain transfer agent and using different tapered block copolymers as the precursor rubber
Authors: de León Ramon Díaz , Morales Graciela , Acuña Pablo , Soriano Florentino
Published: September 2009

Different high impact polystyrenes were synthesized using styrene/butadiene copolymers (SB) with PS/PB composition: 30/70 and 20/80 as the precursor rubber, benzoyl peroxide (BPO) as the initiator, and ter‐dodecyl mercaptane (TDM) as the chain transfer agent. During the polymerization, several samples were taken and analyzed under different techniques to evaluate the phase inversion (PI) phenomenon. The PI was determined through transmission electron microscopy (TEM) and through dynamic oscillatory behavior, where the PI takes places when the relaxation process presents the lower value of activation energy. Finally, the Choi and Schowalter emulsion model was employed to elucidate the PI, and relevant information was revealed about the interfacial tension in the PI. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers
Pain and hip lateral rotator muscle strength contribute to functional status in females with patellofemoral pain
Authors: Long‐Rossi Frances , Salsich Gretchen B.
Published: September 2009

Background and Purpose. Patellofemoral pain (PFP) is a common musculoskeletal pain condition, especially in females. Decreased hip muscle strength has been implicated as a contributing factor, yet the relationships between pain, hip muscle strength and function are not known. The purpose of this study was to test the hypothesis that pain and hip muscle strength explain unique portions of variance in the functional status of females with PFP. Methods. An observational, cohort study was conducted. The subjects for this study were twenty‐one females with PFP (age: 26 ± 7 years; height: 163 ± 4 cm; and body mass: 62 ± 10 kg). Subjects had a minimum pain duration of two months (mean pain duration: 4.9 ± 3.6 years). The main measures were pain during a unilateral squat, measured with a visual analogue scale; isometric muscle force of gluteus medius, gluteus maximus and hip lateral rotators; and Kujala score (self‐report measure of function). Hierarchical multiple regression analysis was performed with Kujala score as the dependent variable. Pain and hip lateral rotator muscle strength were independent variables, entered in that order. Other strength measures were not correlated with the Kujala score, and as such, were not used in the analysis. Results. Pain explained 22% of the variance in the Kujala score (p = 0.03). Hip lateral rotator strength explained an additional 14% of the variance, after accounting for pain level (p = 0.06). Conclusions. Pain and hip lateral rotator strength contributed to the functional status of females with PFP. Improving pain and hip lateral rotator muscle strength may improve function in females with this common pain condition. Copyright © 2009 John Wiley & Sons, Ltd.
Cell‐autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells
Authors: Vander Griend Donald J. , D'Antonio Jason , Gurel Bora , Antony Lizamma , DeMarzo Angelo M. , Isaacs John T.
Published: September 2009

BACKGROUND

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR‐mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell‐dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways.

METHODS

We utilized clinical samples, animal models and a series of AR‐positive human prostate cancer cell lines to evaluate AR‐mediated growth stimulation of prostate CICs.

RESULTS

The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR‐positive human prostate cancer metastases (N = 127) are characteristically AR‐negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR‐positive prostate cancer cells grow equally well when xenografted in wild‐type versus AR‐null nude mice. AR‐dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti‐androgen plus/or minus preconditioned media.

CONCLUSIONS

AR‐induced growth stimulation of human prostate CICs requires AR‐dependent intracellular pathways. The identification of such AR‐dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. Prostate 70: 90–99, 2010. © 2009 Wiley‐Liss, Inc.
Tumor suppressor PAX6 functions as androgen receptor Co‐repressor to inhibit prostate cancer growth
Authors: Shyr Chih‐Rong , Tsai Meng‐Yin , Yeh Shuyuan , Kang Hong‐Yo , Chang Yun‐Chao , Wong Pei‐Ling , Huang Chao‐Cheng , Huang Ko‐En , Chang Chawnshang
Published: September 2009

BACKGROUND

PAX6, a transcription factor, has currently been suggested to function as a tumor suppressor in glioblastoma and to act as an early differentiation marker for neuroendocrine cells. The androgen receptor (AR) plays a pivotal role in prostate cancer development and progression due to its transcriptional activity in regulating genes involved in cell growth, differentiation, and apoptosis. To determine the role of PAX6 in prostate cancer, we investigated whether PAX6 interacts with AR to affect prostate cancer development.

METHODS

We used immunostaining, RT‐PCR, and Western blotting assays to show the expression status of PAX6 in prostate tissue and human prostate cancer cell lines. The role of PAX6 in cell growth and colony regeneration potential of LNCaP cells were evaluated by MTT assay and soft agar assay with PAX6‐overexpressed LNCaP cells. Mammalian two‐hybrid and co‐immunoprecipitation (Co‐IP) assays were used to demonstrate the interaction between PAX6 and AR. Reporter gene and Q‐RT‐PCR assays were performed to determine the effects of PAX6 on the function of AR.

RESULTS

In prostate cancer tissues, PAX6 expression was stronger in normal epithelial cells than cancer cells, and decreased in LNCaP cells compared to that of DU145 and PC3 cells. Enforced expression of PAX6 suppressed the cell growth of LNCaP cells and also inhibited the colony formation of LNCaP cells. PAX 6 interacted with AR and repressed its transcriptional activity. PAX6 overexpression decreased the expression of androgen target gene PSA in LNCaP cells.

CONCLUSIONS

In this study, we found that PAX6 may act as a prostate cancer repressor by interacting with AR and repressing the transcriptional activity and target gene expression of AR to regulate cell growth and regeneration. Prostate 70: 190–199, 2010. ©2009 Wiley‐Liss, Inc.
Antisense oligonucleotide targeting of insulin‐like growth factor‐1 receptor (IGF‐1R) in prostate cancer
Authors: Furukawa Junya , Wraight Christopher J. , Freier Susan M. , Peralta Eigan , Atley Lynne M. , Monia Brett P. , Gleave Martin E. , Cox Michael E.
Published: September 2009

OBJECTIVE

Altered expression of insulin‐like growth factor receptor (IGF‐1R) is associated with castrate‐resistant prostate cancer (CRPC) progression. We hypothesize that increased expression and/or responsiveness of IGF‐IR may promote disease progression. This study assesses ATL1101, a 2′‐MOE‐modified antisense oligonucleotide (ASO) targeting human IGF‐IR, with regard to potency and anti‐cancer activity in androgen‐responsive (LNCaP) and ‐independent (PC3) prostate cancer cells in vitro and in vivo.

METHODS

IGF‐IR mRNA and protein expression was assessed in ATL1101‐ and control oligonucleotides (ODN)‐treated prostate cancer cells by QT‐PCR and immunoblotting. The effect of IGF‐1R ASO on cell growth and apoptosis in vitro was examined by crystal violet assay, flow cytometry, and expression and activation state of downstream signaling targets was examined by immunoblotting. In vivo growth of subcutaneous xenografts was performed in nude mice treated with intraperitoneally administered ATL1101 or control ODN by measuring tumor volume of PC3 xenografts in intact mice, and tumor volume and serum prostate‐specific antigen levels in castrated mice harboring LNCaP xenografts.

RESULTS

We observed dose‐ and sequence‐specific suppression of IGF‐IR mRNA and protein expression in ATL1101‐treated cells in vitro. Suppressed IGF‐IR expression correlated with decreased proliferation and increased apoptosis of PC3 cells under standard culture conditions and of LNCaP cells under androgen‐deprived culture conditions. ATL1101 suppressed PC3 tumor growth as a monotherapy and delayed CRPC progression of LNCaP xenografts.

CONCLUSIONS

This study reports the first preclinical proof‐of‐principle data that this novel IGF‐IR ASO selectively suppresses IGF‐1R expression, suppresses growth of CRPC tumors, and delays CRPC progression in vitro and in vivo. Prostate 70: 206–218, 2010. ©2009 Wiley‐Liss, Inc.
Docetaxel–ST1481 sequence exerts a potent cytotoxic activity on hormone‐resistant prostate cancer cells by reducing drug resistance‐related gene expression
Authors: Fabbri Francesco , Brigliadori Giovanni , Carloni Silvia , Ulivi Paola , Tesei Anna , Silvestrini Rosella , Amadori Dino , Zoli Wainer
Published: September 2009

BACKGROUND

The efficacy of current therapy for hormone‐refractory prostate cancer is still unsatisfactory and new agents and therapeutic modalities are needed. The aims of the present work were to examine the in vitro activity and mechanisms of action of different antitumor drug combinations in hormone‐resistant prostate cancer (HRPC) cell lines.

METHODS

The activity of docetaxel (Doc), cisplatin (Cis), oxaliplatin (Oxa), SN‐38 and ST1481, singly or in combination, was assessed in different HRPC cell lines (PC3, parental DU145 and taxane‐resistant DU145‐R) by SRB test. Apoptosis was evaluated by TUNEL and ANN‐V assays. Extrusion pump activity was studied by Hoechst 33342 assay, while gene expression related to drug efflux mechanisms and DNA damage repair was analyzed by RT‐PCR.

RESULTS

Doc induced a high cytocidal effect in the HRPC cells, whereas Cis, Oxa, SN‐38 and ST1481 exerted prevalently cytostatic activity. Doc followed by ST1481 proved to be the most effective drug sequence among those investigated, producing an important synergistic effect (R.I. from 2.0 to 5.2) in all the tested cell lines. Moreover, this sequence induced a significant downregulation of xenobiotic extrusion pump and DNA damage repair gene expression. ST1481 synergistically increased the cytocidal effect of Doc, probably through a downregulation of extrusion pump activity and DNA damage repair‐related genes.

CONCLUSIONS

Our results show that the Doc → ST1481 sequence effectively reduces the cancer cell population and restores Doc activity in taxane‐resistant HRPC, indicating its potential usefulness as first‐ or second‐line treatment of hormone‐refractory prostate cancer. Prostate 70: 219–227, 2010. ©2009 Wiley‐Liss, Inc.
Arachidonic acid activation of intratumoral steroid synthesis during prostate cancer progression to castration resistance
Authors: Locke Jennifer A. , Guns Emma S. Tomlinson , Lehman Melanie L. , Ettinger Susan , Zoubeidi Amina , Lubik Amy , Margiotti Katia , Fazli Ladan , Adomat Hans , Wasan Kishor M. , Gleave Martin E. , Nelson Colleen C.
Published: September 2009

BACKGROUND

De novo androgen synthesis and subsequent androgen receptor (AR) activation has recently been shown to contribute to castration‐resistant prostate cancer (CRPC) progression. Herein we provide evidence that fatty acids (FA) can trigger androgen synthesis within steroid starved prostate cancer (CaP) tumor cells.

METHODS

Tumoral FA and steroid levels were assessed by GC–MS and LC–MS, respectively. Profiles of genes and proteins involved in FA activation of steroidogenesis were assessed by fluorescence microscopy, immunohistochemistry, microarray expression profiling and Western blot analysis.

RESULTS

In human CaP tissues the levels of proteins responsible for FA activation of steroid synthesis were observed to be altered during progression to CRPC. Further investigating this mechanism in LNCaP cells, we demonstrate that specific FA, arachidonic acid, is synthesized in an androgen‐dependent and AR‐mediated manner. Arachidonic acid is known to induce steroidogenic acute regulatory protein (StAR) in steroidogenic cells. When bound to hormone sensitive lipase (HSL), StAR shuttles free cholesterol into the mitochondria for downstream conversion into androgens. We show that arachidonic acid induces androgen production in steroid starved LNCaP cells coincidently in the same conditions that HSL and StAR are predominantly localized in the mitochondria. Furthermore, their activities are verified by a functional increase in mitochondrial uptake of cholesterol in this steroid starved environment.

CONCLUSIONS

We propose that this characterized arachidonic acid induced steroidogenesis mechanism significantly contributes to the activation of AR in CRPC progression and therefore recommend that fatty acid pathways be targeted therapeutically in progressing CaP. Prostate 70: 239–251, 2010. © 2009 Wiley‐Liss, Inc.
Antiandrogen withdrawal syndrome and alternative antiandrogen therapy associated with the W741C mutant androgen receptor in a novel prostate cancer xenograft
Authors: Terada Naoki , Shimizu Yosuke , Yoshida Toru , Maeno Atsushi , Kamba Tomomi , Inoue Takahiro , Nakamura Eijiro , Kamoto Toshiyuki , Ogawa Osamu
Published: September 2009

BACKGROUND

The mechanisms underlying antiandrogen withdrawal syndrome (AWS) and alternative antiandrogen therapy (AAT) effectiveness were assumed to be mutations in the androgen receptor (AR), which resulted in an altered response to antiandrogens. The aim of the present study was to test this assumption using the novel prostate cancer xenograft model KUCaP‐1 harboring the W741C mutant AR (Yoshida et al., Cancer Res 2005; 65(21): 9611–9616).

METHODS

Mice bearing xenograft tumors were castrated, and the long‐term sequential changes in tumor volume were observed. To determine whether AWS was observed in this model, bicalutamide (BCL) was orally administered to the castrated mice and then withdrawn. The effect of flutamide (FLT) on the W741C mutant AR was examined with transactivation assays in vitro and with the oral administration of FLT to non‐castrated mice harboring KUCaP‐1 in vivo. The AAT efficacy against KUCaP‐1 was evaluated by changing BCL with FLT.

RESULTS

KUCaP‐1 regressed significantly after castration and did not re‐grow. KUCaP‐1 treated with BCL continued to grow even after castration and started regressing 2 months after BCL withdrawal, replicating clinically recognized AWS. The antagonistic effect of FLT against the W741C mutant AR was revealed in vitro and in vivo. AAT with FLT suppressed tumor growth after BCL withdrawal.

CONCLUSIONS

KUCaP‐1 was an entirely androgen‐dependent xenograft and mimicked the clinical phenomena of AWS and AAT caused by the agonistic and antagonistic activity of BCL and FLT, respectively. KUCaP‐1 could be an in vivo model for screening novel antiandrogens for the treatment of BCL resistant prostate cancer harboring the W741C mutation in the AR. Prostate 70: 252–261, 2010. © 2009 Wiley‐Liss, Inc.
The pH sensitivity of histidine‐contain‐ ing lytic peptides
Authors: Tu Zhigang , Young Albert , Murphy Christopher , Liang Jun F.
Published: September 2009

Many bioactive peptides are featured by their unique amino acid compositions such as argine/lysine‐rich peptides. However, histidine‐rich bioactive peptides are hardly found. In this study, histidine‐containing peptides were constructed by selectively replacing the corresponded lysine residues in a lytic peptide LL‐1 with histidines. Interestingly, all resulting peptides demonstrated pH‐dependent activities. The cell lysis activities of these peptides could be increased up to four times as the solution pHs dropped from pH = 7.4 to pH = 5.5. The pH sensitivity of a histidine‐containing peptide was determined by histidine substitution numbers. Peptide derivatives with more histidines were associated with increased pH sensitivity. Results showed that not the secondary structures but pH‐affected cell affinity changes were responsible for the pH‐dependent activities of histidine‐containing peptides. The histidine substitution approach demonstrated here may present a general strategy to construct bioactive peptides with desired pH sensitivity for various applications. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.
Supreme shear modulus predicted in the monocarbide system: the Rex W1–xC alloy
Authors: Zhang Xinyu , Chen Zhouwen , Fan Changzeng , Ma Mingzhen , Jing Qin , Liu Riping
Published: September 2009

The energetic, mechanical and electronic properties as a function of composition for Rex W1–x C alloys in the WC structure have been investigated. It has been demonstrated that the shear modulus of WC can be enhanced by alloying with a small amount of Re, to a maximum shear modulus of 311 GPa at x = 0.23. The designed alloy is energetically stable and could be expected to be a potential extremely hard transition‐metal monocarbide, which is attributed to the strong metal–metalloid interaction with modulated valence electron concentration with respect to WC. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)