bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Survival after Resuscitation with Norepinephrine in a Murine Model of Uncontrolled Hemorrhagic Shock
Authors: Poloujadoff Marie-Pierre , Borron Stephen W. , Amathieu Roland , Favret Fabrice , Camara Mamadou S. , Lapostolle Frédéric , Vicaut Eric , Adnet Frédéric 
Published: March 2009

Background
Recent studies have challenged current guidelines on fluid resuscitation. However, studies on resuscitation using norepinephrine in uncontrolled hemorrhagic shock are lacking. The authors examined the effects of norepinephrine in combination with saline infusion in uncontrolled hemorrhage in rats.

Methods
Rats subjected to a 15-min controlled hemorrhage (withdrawal of 3 ml blood/100 g body mass) followed by a 60-min uncontrolled hemorrhage (75% tail amputation) were randomly assigned to one of several treatment groups (10 rats/group) receiving different doses of norepinephrine (0 [NE0], 5 [NE5], 50 [NE50], or 500 [NE500] microg.100 g(-1).h(-1)). In the four hypotensive resuscitation groups (n = 40), mean arterial pressure was not allowed to fall below 40 mmHg by titrated infusion of normal saline. In the four normotensive resuscitation groups (n = 40), it was not allowed to fall below 80 mmHg. The endpoint was survival at 210 min.

Results
There was a significant difference (P < 0.05) in survival rate among groups. Among the hypotensive rats, 6 (60%) survived in the NE0 and NE5 dose groups, 9 (90%) survived in the NE50 dose group, and none survived in the NE500 dose group. Among the normotensive rats, none survived in the NE0 group, 4 (40%) survived in the NE5 dose group, all 10 (100%) survived in the NE50 group, and none survived in the NE500 group.

Conclusions
The early use of norepinephrine in uncontrolled hemorrhagic shock in rats significantly improved survival when infused at a rate of 50 microg.100 g(-1).h(-1) in normotensive and hypotensive resuscitation strategies.
Percutaneous Aortic Valve Replacement
Authors: Quaden René , Attmann Tim , Klaws Günther-Rudolf , Schünke Michael , Theisen-Kunde Dirk , Lozonschi Lucian , Cremer Jochen , Lutter Georg 
Published: March 2009

Objective To improve the outcome of percutaneous valve replacement in aortic stenosis endovascular resection of calcified aortic valves will be necessary. In this study different sealing methods were evaluated. The focus of this research was feasibility and mechanical functionality in human anatomy. Methods The aortic valve isolation chamber (AVIC) is a catheter-based system to seal the aortic valve during resection, and was installed antegrade and retrograde. Firstly, AVIC was inserted antegrade via the cardiac apex in human postmortem models (n = 2), and secondly in porcine in vivo models under extra corporeal circulation (n = 5). Endoscopic inspection of the valve was recorded. AVIC was installed via a port system through the descending aorta. Micro- and macropathologies were performed. Results AVIC transapical deployment in the two human models took 3 and 4 minutes respectively and 2.2 ± 1.3 minutes in average in the porcine model. From the descending aorta, the deployment took 9.3 ± 5.5 minutes. Fluoroscopy and macroscopy demonstrated sealed chambers. Microscopic and histologic analysis demonstrated no profound damages of the surrounding tissue. Conclusion This study demonstrates the feasibility of transapical and retrograde endovascular sealing of the aortic valve in vitro and in vivo in nonbeating hearts.
Rising Incidence of Oropharyngeal Cancer and the Role of Oncogenic Human Papilloma Virus
Authors: Ernster Joel A. , Sciotto Cosimo G. , O'Brien Maureen M. , Finch Jack L. , Robinson Linda J. , Willson Thomas , Mathews Michael 
Published: March 2009

AbstractObjectives/Hypothesis: To document the increasing incidence of oropharyngeal (OP) cancer and to provide evidence that this increase is caused by oncogenic human papilloma virus (HPV).Study Design: Epidemiologic review and retrospective case series analysis.Methods: We collected data from Colorado and the United States comparing the average annual age‐adjusted incidence rates of OP and non‐OP head and neck cancer between the periods 1980 to 1990 and 1991 to 2001. We obtained data on 72 patients with OP cancer from a single county in Colorado, from 1980 through 2004. HPV status was determined by DNA‐polymerase chain reaction. We assessed disease‐specific survival.Results: The average annual age‐adjusted incidence of OP cancer in males in Colorado increased from 2.54 per 100,000 to 3.47 (P < .05) or 36.6%, whereas the U.S. rate increased from 4.34 to 4.81 (P < .05) or 10.8%. The rates in females and the rates of non‐OP head and neck cancer decreased. Of the 72 cases, 50 (69%) were positive for HPV subtype 16. The ratio of HPV‐positive to HPV‐negative cases prior to 1995 was 0.72 (8:11) but was 3.81 (42:11) afterward. Survival was positively affected by HPV status (hazard ratio of 0.15, confidence intervals 0.07–0.36, P < .001). Disease‐specific survival was 83% in the HPV‐positive patients and 15% in the HPV‐negative group.Conclusions: OP cancer incidence is increasing in Colorado males and to a lesser extent in U.S. males. The HPV‐positive OP cancer cases were more frequent in the later years of the study. Disease‐specific survival was much better in the HPV‐positive patients, confirming that HPV testing defines a unique subset of patients. These findings suggest that HPV oncogenesis accounts for the increase in average annual age‐adjusted incidence of OP cancer.
Deferring Planned Neck Dissection Following Chemoradiation for Stage IV Head and Neck Cancer: The Utility of PET‐CT
Authors: Nayak Jayakar V. , Walvekar Rohan R. , Andrade Regiane S. , Daamen Nicole , Lai Stephen Y. , Argiris Athanassios , Smith Ryan P. , Heron Dwight E. , Ferris Robert L. , Johnson Jonas T. , Branstetter Barton F. 
Published: March 2009

AbstractObjective: To determine whether combined positron emission tomography and computed tomography (PET‐CT) may be of value in deferring planned neck dissections for patients with advanced head and neck squamous cell carcinoma (HNSCC).Study Design: Observational study of patients with de novo cervical ≥N2 regional spread of HNSCC in a tertiary care academic medical center.Methods: Forty‐three patients were identified who underwent post‐treatment PET‐CT within 6 months of completing neoadjuvant chemotherapy combined with radiation therapy (CRT). The PET‐CT was “positive” if the radiologist recommended tissue sampling or resection of cervical lymph nodes, or if there was progressive neck disease in the setting of distant metastatic disease. Patients who had positive PET‐CT underwent confirmatory biopsy given clinical suspicion for regional cervical metastasis without distant disease. Patients with negative PET‐CT were followed clinically and radiographically for a minimum of 5 months (median 18.1 months) after CRT.Results: Ten (22%) of the 43 post‐treatment PET‐CT studies were positive. Seven of the 10 PET‐CT scans (70% of positives) were true‐positive given histologically‐confirmed residual viable tumor or progressive disease including disease in the neck. The 3 remaining studies (30% of positives) were false‐positive PET‐CT results, given resolution of fluorodeoxyglucose (FDG) avidity on subsequent imaging or tissue sampling demonstrating absence of viable tumor cells. Of the 33 patients with negative PET‐CTs in the neck, 1 patient had absence of FDG‐avidity in the setting of malignant disease in the neck (3% false negatives); otherwise, patients with an initially negative PET‐CT scan had no recurrences during the study (97% true negatives). This corresponds to a sensitivity of 87.5% (7/8), a specificity of 91% (32/35), a positive predictive value of 70% (7/10), a negative predictive value of 97% (32/33), and accuracy of 91% (39/43) for PET‐CT scans in the detection of cervical metastatic disease after CRT. Overall, 37 (86%) of 43 patients were spared neck dissection using this technology without evidence of recurrent disease in the neck at extended follow‐up.Conclusions: Our results suggest that planned neck dissection after CRT for HNSCC may be deferred in favor of serial PET‐CT imaging, and that sampling of areas of suspicious FDG‐avid uptake can be rationally considered prior to therapeutic neck dissection. These data also suggest that negative PET‐CT scans are highly reliable for the absence of residual cervical nodal disease.
Expression of Fas and Fas ligand in human testicular germ cell tumours
Authors: Baldini E. , Ulisse S. , Marchioni E. , Di Benedetto A. , Giovannetti G. , Petrangeli E. , Sentinelli S. , Donnorso R. P. , Reale M. G. , Mottolese M. , Gandini L. , Lenzi A. , D’Armiento M. 
Published: March 2009

SummaryIn the present study, we analysed the expression of Fas ligand (FasL) and its cognate receptor Fas in 14 seminomatous testicular germ cell tumours (TGCT) and six normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for immunohistochemistry (IHC) experiments. Quantitative RT‐PCR experiments demonstrated in TGCT a significant (p < 0.01) increase of the FasL mRNA expression of 21.1 ± 5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues, the levels of Fas mRNA were significantly (p < 0.01) reduced to 0.27 ± 0.06 fold. These observations were confirmed in western blot experiments showing a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. Moreover, IHC experiments showed a strong FasL immuno‐reactivity in six out of eight TGCT samples analysed, while Fas immuno‐positivity was found in cancer cells of only two TGCT tissues. In addition, in all tumour samples, infiltrating lymphocytes were Fas positive. However, no correlation could be observed between Fas or FasL mRNA variations and clinical parameters such as patient’s age, TNM stage or tumour size. We also compared the serum levels of soluble FasL (sFasL) of 15 patients affected by seminomatous TGCT, of four patients with non‐seminomatous TGCT and six age‐matched healthy males. No significant differences in sFasL serum level could be identified. In conclusion, our data demonstrated that the majority of seminomas are characterized by an increased expression of FasL and a concomitant reduction of Fas, with respect to human normal testis, and that sFasL serum level is not a tumour marker for patients affected by TGCT.
NMR structure of a fungal virulence factor reveals structural homology with mammalian saposin B
Authors: Beck Moriah R. , DeKoster Gregory T. , Cistola David P. , Goldman William E. 
Published: March 2009

SummaryThe fungal protein CBP (calcium binding protein) is a known virulence factor with an unknown virulence mechanism. The protein was identified based on its ability to bind calcium and its prevalence as Histoplasma capsulatum's most abundant secreted protein. However, CBP has no sequence homology with other CBPs and contains no known calcium binding motifs. Here, the NMR structure of CBP reveals a highly intertwined homodimer and represents the first atomic level NMR model of any fungal virulence factor. Each CBP monomer is comprised of four α‐helices that adopt the saposin fold, characteristic of a protein family that binds to membranes and lipids. This structural homology suggests that CBP functions as a lipid binding protein, potentially interacting with host glycolipids in the phagolysosome of host cells.
Control of Pseudomonas aeruginosa AlgW protease cleavage of MucA by peptide signals and MucB
Authors: Cezairliyan Brent O. , Sauer Robert T. 
Published: March 2009

SummaryThe ability of a pathogen to survive the defensive attacks of its host requires the detection of and response to perturbations in its own physiology. Activation of the extracytoplasmic stress response in the pathogen Pseudomonas aeruginosa results in higher tolerance against immune defences as well as in the production of alginate, a surface polysaccharide that also confers resistance to many host defences and antibiotic treatments. The alginate response is regulated by proteolytic cleavage of MucA, a transmembrane protein that inhibits the transcription factor AlgU, and by the periplasmic protein MucB. Here we show that specific peptides bind to the periplasmic AlgW protease and activate its cleavage of MucA. We demonstrate that tight binding of MucB to MucA strongly inhibits this cleavage. We also probe the roles of structural features of AlgW, including a key regulatory loop and its PDZ domain, in regulating substrate binding and cleavage.
A randomized trial of lower leg and height growth in children with asthma treated with inhaled budesonide from a new dry powder inhaler
Authors: Gradman Josefine , Wolthers Ole D. 
Published: March 2009

Gradman J, Wolthers OD. A randomized trial of lower leg and height growth in children with asthma treated with inhaled budesonide from a new dry powder inhaler. Pediatr Allergy Immunol 2010: 21: e206–e212. © 2009 The Authors Journal compilation © 2009 Blackwell MunksgaardShort‐term knemometry is a highly sensitive and accurate method for non‐invasive assessment of systemic activity of inhaled corticosteroids in children with asthma. However, there are no randomized data available to elucidate the relation between inhaled corticosteroid suppressed short‐term lower leg and height growth. The aim of the present study was to assess the relation between short‐term lower leg and 1‐yr height growth in children with asthma treated with inhaled budesonide from the new Pulairmax® inhaler 200 μg once daily in the morning or montelukast 5 mg once daily. A total of 52 pre‐pubertal children with asthma were included in a randomized open‐label parallel group study. Length of the lower leg and height were measured by knemometry and stadiometry, respectively, at study entry and after 2, 4, 12, 20, 28, 36, 44 and 52 wks. Lower leg and height growth rates were significantly lower in the budesonide than in the montelukast group (p < 0.0001). Mean 2‐wks lower leg growth rate was 0.17 mm/wk in the budesonide and 0.39 mm/wk in the montelukast treated children (p = 0.02). Mean 1‐yr height growth rate was 5.51 cm/yr in the budesonide and 6.51 cm/yr in the montelukast group [95% CI: (0.20; 1.79)]. There was a strong linear correlation between lower leg and height growth in both groups, rho = 0.96 (budesonide) and 0.98 (montelukast). In conclusion, 1‐yr height growth suppression of budesonide 200 μg administered via the Pulairmax® inhaler once daily in the morning was indicated from suppressed short‐term lower leg growth providing evidence that short‐term knemometry is able to predict 1‐yr height growth suppression of inhaled corticosteroids. Short‐term knemometry should be performed as part of the safety assessments of new inhaled corticosteroids and inhalation devices in children with asthma before long‐term height growth evaluations are initiated.
Mental health services for people with intellectual disability: challenges to care delivery
Authors: Chaplin Eddie , O’Hara Jean , Holt Geraldine , Bouras Nick 
Published: March 2009

Accessible summary

This paper looks at how care is given to people with intellectual disability who have mental health problems.
The paper looks at care since Valuing People came out in 2001.
It shows there are not enough services for people with intellectual disability who have mental health problems.
It shows there are not enough services for people who have autism and mental health problems.
Lots of people feel that mainstream mental health services are not good enough for people with intellectual disability. Lots of people feel mainstream services could be better.
The paper looks at how people can get help and support in their local area and not having to move away to get help.
The paper looks at what services might be needed in the future. What can be done to make services better?
The people who pay for services are called commissioners. They should think about how they can make local services better for with intellectual disability and mental health problems.
Commissioners should work more together with those who support people with intellectual disability to improve services.
People with intellectual disability should be happy with the services they have in their local places.
Services need to remember that people change as they get older.
Services need to remember that what people want. This can change when they get older.

SummaryThe commissioning and provision of mental health services for people with intellectual disability is often complex and characterised by different service delivery models. This paper looks at the current situation 7 years after the White Paper, Valuing People (From words into action: London learning disabilities strategic framework, Department of Health, London), within the context of the National Service Framework for Mental Health (Establishing responsible commissioner; draft guidance. HSC draft, Department of Health, London). It sets out to illustrate problems faced in providing local services in the United Kingdom for those with intellectual disability and other neurodevelopmental disorders. This paper proposes new ways of working and introduces the concept of a neurodevelopmental model designed to address gaps and inequalities within services by offering solutions that embrace joint working.
The transferable placebo effect from pain to emotion: Changes in behavior and EEG activity
Authors: Zhang Wencai , Luo Jing 
Published: March 2009

AbstractPast studies indicate that the placebo expectation established by analgesic treatment significantly relieves pain perception, while ataractic treatment significantly alleviates unpleasant arousal evoked by negative picture processing. But it is unclear whether the placebo effect can be transferred from one domain to the other, namely from pain to emotion. In this study we led participants to believe in the analgesic effect of magnetic treatment equipment (the placebo) by secretly reducing the intensity of pain stimulus. Then, we examined if this placebo could significantly alter participants' negative affect evoked by watching unpleasant pictures. Our results indicated a significant transferable placebo effect that alleviated negative feelings. EEG recordings showed the transferable placebo treatment induced decreased P2 amplitude and increased N2 amplitude, with source location near the posterior cingulate.
Combined Ultrasound and Nerve Stimulation‐Guided Thoracic Epidural Catheter Placement for Analgesia Following Anterior Spine Fusion in Scoliosis
Authors: Pandin Pierre , Haentjens Lionel , Salengros Jean Corentin , Quintin Jeam , Barvais Luc 
Published: March 2009

AbstractAnterior spine fusion by thoracotomy is indicated for the treatment of idiopathic scoliosis. Although epidural (EP) analgesia represents the most effective way to provide adequate analgesia after thoracotomy, scoliosis patients have substantial anatomic variations that make EP catheter placement more difficult and often contraindicated. This case report describes a safe, effective technique for placing a thoracic EP catheter in a young patient undergoing anterior spine fusion surgery by thoracotomy. The procedure was guided by both ultrasound (US) and electrical stimulation of the Tuohy needle and catheter. The combination of US and nerve stimulation in this setting may be associated with easier, potentially safer, and more accurate insertion.
Small Molecule XIAP Inhibitors Enhance TRAIL-Induced Apoptosis and Antitumor Activity in Preclinical Models of Pancreatic Carcinoma
Authors: Vogler Meike , Walczak Henning , Stadel Dominic , Haas Tobias L. , Genze Felicitas , Jovanovic Marjana , Bhanot Umesh , Hasel Cornelia , Möller Peter , Gschwend Jürgen E. , Simmet Thomas , Debatin Klaus-Michael , Fulda Simone 
Published: March 2009

Abstract
Evasion of apoptosis is a characteristic feature of pancreatic cancer, a prototypic cancer that is refractory to current treatment approaches. Hence, there is an urgent need to design rational strategies that counter apoptosis resistance. To explore X-linked inhibitor of apoptosis (XIAP) as a therapeutic target in pancreatic cancer, we analyzed the expression of XIAP in pancreatic tumor samples and evaluated the effect of small molecule XIAP inhibitors alone and in combination with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) against pancreatic carcinoma in vitro and in vivo. Here, we report that XIAP is highly expressed in pancreatic adenocarcinoma samples compared with normal pancreatic ducts. Small molecule XIAP inhibitors synergize with TRAIL to induce apoptosis and to inhibit long-term clonogenic survival of pancreatic carcinoma cells. In contrast, they do not reverse the lack of toxicity of TRAIL on nonmalignant cells in vitro or normal tissues in vivo, pointing to a therapeutic index. Most importantly, XIAP inhibitors cooperate with TRAIL to trigger apoptosis and suppress pancreatic carcinoma growth in vivo in two preclinical models, i.e., the chorioallantoic membrane model and a mouse xenograft model. Parallel immunohistochemical analysis of tumor tissue under therapy reveals that the XIAP inhibitor acts in concert with TRAIL to cause caspase-3 activation and apoptosis. In conclusion, our findings provide, for the first time, evidence in vivo that XIAP inhibitors prime pancreatic carcinoma cells for TRAIL-induced apoptosis and potentiate the antitumor activity of TRAIL against established pancreatic carcinoma. These findings build the rationale for further (pre)clinical development of XIAP inhibitors and TRAIL against pancreatic cancer. [Cancer Res 2009;69(6):2425–34]
Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma
Authors: Avnet Sofia , Sciacca Laura , Salerno Manuela , Gancitano Giovanni , Cassarino Maria Francesca , Longhi Alessandra , Zakikhani Mahvash , Carboni Joan M. , Gottardis Marco , Giunti Armando , Pollak Michael , Vigneri Riccardo , Baldini Nicola 
Published: March 2009

Abstract
Despite the frequent presence of an insulin-like growth factor I receptor (IGFIR)-mediated autocrine loop in osteosarcoma (OS), interfering with this target was only moderately effective in preclinical studies. Here, we considered other members of the IGF system that might be involved in the molecular pathology of OS. We found that, among 45 patients with OS, IGF-I and IGFBP-3 serum levels were significantly lower, and IGF-II serum levels significantly higher, than healthy controls. Increased IGF-II values were associated with a decreased disease-free survival. After tumor removal, both IGF-I and IGF-II levels returned to normal values. In 23 of 45 patients, we obtained tissue specimens and found that all expressed high mRNA level of IGF-II and &gt;IGF-I. Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HRA). These receptors were also expressed in OS cell lines, and simultaneous impairment of IGFIR, IR, and Hybrid-Rs by monoclonal antibodies, siRNA, or the tyrosine kinase inhibitor BMS-536924, which blocks both IGFIR and IR, was more effective than selective anti-IGFIR strategies. Also, anti–IGF-II-siRNA treatment in low-serum conditions significantly inhibited MG-63 OS cells that have an autocrine circuit for IGF-II. In summary, IGF-II rather than IGF-I is the predominant growth factor produced by OS cells, and three different receptors (IR-A, HRA, and IGFIR) act complementarily for an IGF-II–mediated constitutive autocrine loop, in addition to the previously shown IGFIR/IGF-I circuit. Cotargeting IGFIR and IR-A is more effective than targeting IGF-IR alone in inhibiting OS growth. [Cancer Res 2009;69(6):2443–52]