bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and evaluation of a multi-epitope assembly Peptide (MEAP) against herpes simplex virus type 2 infection in BALB/c mice
Authors: Wang Xingsheng , Xie Guangyan , Liao Jianming , Yin Dengke , Guan Wenyan , Pan Mingjie , Li Jingnian , Li Yuexi 
Published: May 2011

AbstractBackgroundHuman herpes simplex virus (HSV) 1 and 2 causes oral, ocular, or genital infections, which remains a significant health problem worldwide. HSV-1 and -2 infections in humans range from localized skin infections of the oral, ocular, and genital regions to severe and often disseminated infections in immunocompromised hosts. Epitope based vaccination is a promising mean to achieve protective immunity and to avoid infections with Human herpes simplex virus type 2 (HSV-2).MethodsThe twelve selected epitopes, six B cell epitopes from different glycoprotein of HSV-2 (amino acid residues 466-473 (EQDRKPRN) from envelope glycoprotein B, 216-223 (GRTDRPSA) from C, 6-18 (DPSLKMADPNRFR) from D, 483-491 (DPPERPDSP) from E, 572-579 (EPPDDDDS) from G and 286-295 (CRRRYRRPRG) from I glycoprotein of HSV-2), four CD4+T cell epitopes (amino acid residues 21-28 (NLPVLDQL) from D, 162-177 (KDVTVSQVWFGHRYSQ) from B, 205-224 (KAYQQGVTVDSIGMLPRFIP) from D and 245-259 (KPPYTSTLLPPELSD) from D) and two CD8+T cell epitopes (amino acid residues 10-20 (KMADPNRFRGK) from D and 268-276 (ALLEDPAGT) from D), are responsible for the elicitation of the neutralizing antibodies and cytotoxic T lymphocytes (CTLs) that impart protective immunity to the host. In this study, all above epitopes were inserted into the extracellular fragment (amino acid residues 1-290) of HSV-2 glycoprotein D to construct multi-epitope assembly peptides (MEAPs) by replacing some non-epitope amino acid sequences. The epitope independency of the MEAPs was predicted by three-dimensional software algorithms. The gene of the selected MEAP was expressed inE.coliBL21(DE3), and its protective efficacy against HSV-2 infection was assessed in BALB/c mice.ResultsThe MEAP, with each inserted epitopes independently displayed on the molecule surface, was selected as candidate proteins. The results showed that the MEAP was highly immunogenic and could elicit high titer neutralizing antibodies and cell-mediated immune responses.ConclusionsThe MEAP provided complete protection against infection with HSV-2 in mice, which indicates that it might be a potential candidate vaccine against HSV-2.
Laparoscopic insertion of pelvic tissue expander to prevent radiation enteritis prior to radiotherapy for prostate cancer
Authors: McKay Gary D , Wong Karen , Kozman Daniel R 
Published: May 2011

Abstract
Radiation enteritis is a significant complication of external beam radiotherapy (EBRT) to the pelvis, particularly in patients having high dose radiotherapy (>80 Gy) and in those with a low pelvic peritoneal reflection allowing loops of small bowel to enter the radiation field. Laparoscopic insertion and subsequent removal of a pelvic tissue expander before and after external beam radiotherapy is a relatively convenient, safe and effective method for displacing loops of bowel out of the pelvis. We report on a patient with prostate cancer who ordinarily would not have been a candidate for EBRT due to loops of bowel low in the pelvis. With laparoscopic insertion and subsequent removal of a tissue expander, he was able to have radiotherapy to the prostate without developing radiation enteritis.
Degenerative processes in bioprosthetic mitral valves in juvenile pigs
Authors: Honge Jesper L , Funder Jonas A , Pedersen Torben B , Kronborg Mads B , Hasenkam J Michael 
Published: May 2011

Abstract

Background
Glutaraldehyde-treated bioprosthetic heart valves are commonly used for replacement of diseased heart valves. However, calcification and wear limit their durability, and the development of new and improved bioprosthetic valve designs is needed and must be evaluated in a reliable animal model. We studied glutaraldehyde-treated valves 6 months after implantation to evaluate bioprosthetic valve complications in the mitral position in juvenile pigs.

Materials
The study material comprised eight, 5-month old, 60-kg pigs. All pigs received a size 27, glutaraldehyde-treated, stented, Carpentier-Edwards S.A.V. mitral valve prosthesis. After six months, echocardiography was performed, and the valves explanted for gross examination, high resolution X-ray, and histological evaluation.

Results
Five pigs survived the follow-up period. Preexplant echocardiography revealed a median peak and mean velocity of 1.61 m/s (range: 1.17-2.00) and 1.20 (SD = ±0.25), respectively, and a median peak and mean pressure difference of 10.42 mmHg (range: 5.83-16.55) and 6.51 mmHg (SD = ±2.57), respectively. Gross examination showed minor thrombotic depositions at two commissures in two valves and at all three commissures in three valves. High resolution X-ray imaging revealed different degrees of calcification in all explanted valves, primarily in the commissural and belly areas. In all valves, histological evaluation demonstrated various degrees of fibrous sheath formation, limited immunological infiltration, and no overgrowth of host endothelium.

Conclusions
Bioprosthetic glutaraldehyde-treated mitral valves can be implanted into the mitral position in pigs and function after 6 months. Echocardiographic data, calcification, and histological examinations were comparable to results obtained in sheep models and human demonstrating the suitability of the porcine model.
Pharmacological strategies to reduce pruritus during postoperative epidural analgesia after lumbar fusion surgery - a prospective randomized trial in 150 patients
Authors: Gulle Eva , Skärvinge Carola , Runberg Karin , Robinson Yohan , Olerud Claes 
Published: May 2011

Abstract

Background
Epidural analgesia with bupivacain, epinephrine and fentanyl provides excellent pain control after lumbar fusion surgery, but pruritus and motor block are frequent side effects. Theoretically epidural ropivacain combined with oral oxycodone could decrease the incidence of these side effects. The two regimens were compared in a prospective randomized trial.

Patients and methods
150 patients (87 women) treated with posterior instrumented lumbar fusion were included. The mean age was 51 +/- 11 years. 76 were randomized to bupivacain, epinephrine and fentanyl (group B) and 74 to ropivacain and oxycodone (group R). Pruritus, motor block and pain were measured 6 hours after surgery, thereafter 6 times per day for 5 days. Any pain breakthrough episode was registered whenever it occurred.

Results
The epidural treatment could be performed in 143 patients (72 in group B and 71 in group R). Disturbing pruritus occurred in 53 patients in group B compared to 12 in group R (p < 0.0001). Motor blockade was most frequent on day 1, occurring in 45% of the patients with no difference between the groups. Both regimes gave good pain control with average VAS under 40, but the pain relief was statistically better in group B. The number of pain breakthrough episodes did not differ between the groups.

Conclusions
Pruritus could be reduced with a combination of epidural ropivacain and oral oxycodone, at the price of a slightly higher pain level. Ropivacaine was not found to be superior to bupivacaine with regard to motor blocks.
The net cost of incorporating resistance testing into HIV/AIDS treatment in South Africa: a Markov model with primary data
Authors: Rosen Sydney , Long Lawrence , Sanne Ian , Stevens Wendy S , Fox Matthew P 
Published: May 2011

BackgroundCurrent guidelines for providing antiretroviral therapy (ART) in South Africa's public sector programme call for switching patients from first‐line to second‐line treatment upon virologic failure as indicated by two consecutive viral loads above 5000 copies/ml, but without laboratory evidence of viral resistance. We modelled the net cost of adding resistance testing for patients with virological failure and retaining patients without resistance on first‐line therapy, rather than switching all failures to second‐line therapy.MethodsCosts were estimated for three scenarios: routine maintenance (standard care without resistance testing, switch all failures to second line); resistance testing (resistance test for patients with failure, switch those with resistance); and limited testing (resistance test for patients with failure in the first three years, switch those with resistance). A Markov model was used to estimate the cost of each arm over five years after first line initiation. Rates of treatment failure, viral resistance and treatment costs were estimated with primary data from a large HIV treatment cohort at a public facility in Johannesburg. Future costs were discounted at 3%.ResultsVirological failure rates over five years were 19.8% in routine maintenance and 20.2% in resistance testing and limited testing; 16.8% and 11.4% of failures in routine and limited testing, respectively, did not have any resistance mutations, resulting in 3.1% and 2.0% fewer patients switching to second‐line ART by the end of five years. Treatment costs were estimated at US$526 and $1268 per patient per year on first‐line and second‐line therapy, respectively; a resistance test cost $242. The total average cost per patient over five years was $2780 in routine maintenance; $2775 in resistance testing; and $2763 in limited testing.ConclusionsIncorporating resistance testing into treatment guidelines in South Africa is potentially cost‐neutral and can identify other reasons for failure, conserve treatment options, and generate information about emerging resistance patterns.
Randomized, Double-Blind, Placebo-Controlled, Phase II Trial of Sorafenib and Erlotinib or Erlotinib Alone in Previously Treated Advanced Non–Small-Cell Lung Cancer
Authors: Spigel David R. , Burris Howard A. , Greco F. Anthony , Shipley Dianna L. , Friedman Elke K. , Waterhouse David M. , Whorf Robert C. , Mitchell R. Brian , Daniel Davey B. , Zangmeister Jeffrey , Bass J. David , Hainsworth John D. 
Published: May 2011

Purpose Sorafenib, an oral multikinase inhibitor, has shown preliminary activity in non–small-cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with erlotinib with or without sorafenib in this multicenter phase II trial. Patients and Methods Key eligibility criteria included the following: stage IIIB or IV NSCLC; one to two prior regimens; Eastern Cooperative Oncology Group performance status of 0 to 2; and measurable disease. Patients were randomly assigned 2:1 to sorafenib (400 mg orally twice a day) plus erlotinib (150 mg orally daily) or placebo plus erlotinib and stratified by squamous/nonsquamous histology and prior bevacizumab. Treatment efficacy, measured by progression-free survival (PFS) and overall response rate (ORR), was compared. Treatment of 168 patients allowed detection of 40% improvement in the historical PFS of 2.2 months with single-agent erlotinib. Results One hundred sixty-eight patients enrolled from February 2008 to February 2009. Clinical characteristics of the two groups were similar. ORRs for sorafenib/erlotinib and placebo/erlotinib were 8% and 11%, respectively (P = .56); disease control rates were 54% and 38%, respectively (P = .056). Median PFS was 3.38 months for sorafenib/erlotinib versus 1.94 months for placebo/erlotinib (hazard ratio, 0.86; 95% CI, 0.60 to 1.22; P = .196). Seventy-two patients consented to analyses of tumor epidermal growth factor receptor (EGFR). In 67 patients with EGFR wild-type (WT) tumors, median PFS was 3.38 months for sorafenib/erlotinib versus 1.77 months for placebo/erlotinib (P = .018); median overall survival (OS) was 8 months for sorafenib/erlotinib versus 4.5 months for placebo/erlotinib (P = .019). An OS advantage for sorafenib/erlotinib was suggested among 43 patients with fluorescent in situ hybridization (FISH) EGFR-negative tumors (P = .064). Both regimens were tolerable, with modest toxicity increase with sorafenib. Conclusion Although there was little difference in ORR or PFS, subset analyses in EGFR WT and EGFR FISH–negative patients suggest a benefit for the combination of erlotinib/sorafenib compared with single-agent erlotinib with respect to PFS and OS.
Effect of Amifostine on Survival Among Patients Treated With Radiotherapy: A Meta-Analysis of Individual Patient Data
Authors: Bourhis Jean , Blanchard Pierre , Maillard Emilie , Brizel David M. , Movsas Benjamin , Buentzel Jens , Langendijk Johannes A. , Komaki Ritsuko , Swan Leong Swan , Levendag Peter , Pignon Jean Pierre 
Published: May 2011

Purpose Controversy exists regarding whether or not amifostine might reduce the efficacy of cancer treatment. The aim of this meta-analysis was to evaluate the impact of amifostine on overall survival (OS) and progression-free survival (PFS) in patients treated with radiotherapy or chemoradiotherapy. Material and Methods Updated data from individual patients with non–small-cell lung cancer, head and neck squamous cell carcinoma, and pelvic cancer treated with radiotherapy or chemoradiotherapy and randomly assigned to amifostine or not were included. The primary end point was OS. Results Twenty-two randomized trials (2,279 patients) were potentially eligible. Data were available for 16 trials (1,554 patients), but four trials (435 patients) were excluded after data checking. Ultimately 12 trials and 1,119 patients were analyzed. A total of 431 patients were treated with radiotherapy alone (three trials), and 688 patients were treated with chemoradiotherapy (nine trials). Thirty-three percent of patients had lung cancers, 65% had head and neck cancers, and 2% had pelvic carcinomas. Ninety-one percent of patients had locally advanced disease (early stage, 9%). Median follow-up was 5.2 years. The hazard ratio (HR) of death was 0.98 (95% CI, 0.84 to 1.14; P = .78). On the basis of 11 trials (1,091 patients), the HR of progression, relapse, or death was 1.05 (95% CI, 0.90 to 1.22; P = .53). The tests for heterogeneity were not significant (P ≥ .73), and there was no significant variation of treatment effect according to sex, age, tumor site, stage, histology, locoregional treatment, or type of administration for either end point. Conclusion Amifostine did not reduce OS and PFS in patients treated with radiotherapy or chemoradiotherapy.
Prognostic Significance ofASXL1Mutations in Patients With Myelodysplastic Syndromes
Authors: Thol Felicitas , Friesen Inna , Damm Frederik , Yun Haiyang , Weissinger Eva M. , Krauter Jürgen , Wagner Katharina , Chaturvedi Anuhar , Sharma Amit , Wichmann Martin , Göhring Gudrun , Schumann Christiane , Bug Gesine , Ottmann Oliver , Hofmann Wolf-Karsten , Schlegelberger Brigitte , Heuser Michael , Ganser Arnold 
Published: May 2011

PurposeTo study the incidence and prognostic impact of mutations in Additional sex comb-like 1 (ASXL1) in a large cohort of patients with myelodysplastic syndrome (MDS).Patients, Materials, and MethodsOverall, 193 patients with MDS and 65 healthy volunteers were examined for ASXL1 mutations by direct sequencing and for expression levels of ASXL1. The prognostic impact of ASXL1 mutation and expression levels was evaluated in the context of other clinical and molecular prognostic markers.ResultsMutations in ASXL1 occurred with a frequency of 20.7% in MDS (n = 40 of 193) with 70% (n = 28) of mutations being frameshift mutations and 30% (n = 12) being heterozygous point mutations leading to translational changes. ASXL1 mutations were correlated with an intermediate-risk karyotype (P = .002) but not with other clinical parameters. The presence of ASXL1 mutations was associated with a shorter overall survival for frameshift and point mutations combined (hazard ratio [HR], 1.744; 95% CI, 1.08 to 2.82; P = .024) and for frameshift mutations only (HR, 2.06; 95% CI, 1.21 to 3.50; P = .008). ASXL1 frameshift mutations were associated with a reduced time to progression of acute myeloid leukemia (AML; HR 2.35; 95% CI, 1.17 to 4.74; P = .017). In multivariate analysis, when considering karyotype, transfusion dependence, and IDH1 mutation status, ASXL1 frameshift mutations remained an independent prognostic marker in MDS (overall survival: HR, 1.85; 95% CI, 1.03 to 3.34; P = .040; time to AML progression: HR, 2.39; 95% CI, 1.12 to 5.09; P = .024).ConclusionThese results suggest that ASXL1 mutations are frequent molecular aberrations in MDS that predict an adverse prognostic outcome. Screening of patients for ASXL1 mutations might be useful for clinical risk stratification and treatment decisions in the future.
Phase I Study of Oral Azacitidine in Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and Acute Myeloid Leukemia
Authors: Garcia-Manero Guillermo , Gore Steven D. , Cogle Christopher , Ward Renee , Shi Tao , MacBeth Kyle J. , Laille Eric , Giordano Heidi , Sakoian Sarah , Jabbour Elias , Kantarjian Hagop , Skikne Barry 
Published: May 2011

Purpose To determine the maximum-tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic profiles, and clinical activity of an oral formulation of azacitidine in patients with myelodysplastic syndromes (MDSs), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). Patients and Methods Patients received 1 cycle of subcutaneous (SC) azacitidine (75 mg/m2) on the first 7 days of cycle 1, followed by oral azacitidine daily (120 to 600 mg) on the first 7 days of each additional 28-day cycle. Pharmacokinetic and pharmacodynamic profiles were evaluated during cycles 1 and 2. Adverse events and hematologic responses were recorded. Cross-over to SC azacitidine was permitted for nonresponders who received ≥ 6 cycles of oral azacitidine. Results Overall, 41 patients received SC and oral azacitidine (MDSs, n = 29; CMML, n = 4; AML, n = 8). Dose-limiting toxicity (grade 3/4 diarrhea) occurred at the 600-mg dose and MTD was 480 mg. Most common grade 3/4 adverse events were diarrhea (12.2%), nausea (7.3%), vomiting (7.3%), febrile neutropenia (19.5%), and fatigue (9.8%). Azacitidine exposure increased with escalating oral doses. Mean relative oral bioavailability ranged from 6.3% to 20%. Oral and SC azacitidine decreased DNA methylation in blood, with maximum effect at day 15 of each cycle. Hematologic responses occurred in patients with MDSs and CMML. Overall response rate (ie, complete remission, hematologic improvement, or RBC or platelet transfusion independence) was 35% in previously treated patients and 73% in previously untreated patients. Conclusion Oral azacitidine was bioavailable and demonstrated biologic and clinical activity in patients with MDSs and CMML.
Bone reaction to a biomimetic third-generation hydroxyapatite coating and new surface treatment for the Symax hip stem
Authors: ten Broeke R. H. M. , Alves A. , Baumann A. , Arts J. J. C. , Geesink R. G. T. 
Published: May 2011

Four uncemented Symax hip stems were extracted at three weeks and nine, 13 and 32 months, respectively, for reasons other than loosening. The reasons for implant removal were infection in two cases, recurrent dislocation in one and acetabular fracture in one. They were analysed to assess the effect and behaviour of an electrochemically deposited, completely resorbable biomimetic BONIT-hydroxyapatite (HA) coating (proximal part) and a DOTIZE surface treatment (distal part) using qualitative histology, quantitative histomorphometry and scanning electron microscopy (SEM). Early and direct bone-implant bonding with signs of active remodelling of bone and the HA coating were demonstrated by histology and SEM. No loose BONIT-HA particles or delamination of the coating were observed, and there was no inflammation or fibrous interposition at the interface. Histomorphometry showed bone-implant contact varying between 26.5% at three weeks and 83.5% at 13 months at the HA-coated implant surface. The bone density in the area of investigation was between 24.6% at three weeks and 41.1% at 32 months. The DOTIZE surface treatment of the distal part of the stem completely prevented tissue and bone apposition in all cases, thereby optimising proximal stress transfer. The overall features of this implant, in terms of geometry and surface texture, suggest a mechanically stable design with a highly active biomimetic coating, resulting in rapid and extensive osseo-integration, exclusively in the metaphyseal part of the stem. Early remodelling of the HA coating does not seem to have a detrimental effect on short-term bone-implant coupling. There were no adverse effects identified from either the BONIT-HA coating or the DOTIZE surface treatment.
The outcome of fractures in very elderly patients
Authors: Clement N. D. , Aitken S. A. , Duckworth A. D. , McQueen M. M. , Court-Brown C. M. 
Published: May 2011

We compared case-mix and outcome variables in 1310 patients who sustained an acute fracture at the age of 80 years or over. A group of 318 very elderly patients (≥ 90 years) was compared with a group of 992 elderly patients (80 to 89 years), all of whom presented to a single trauma unit between July 2007 and June 2008. The very elderly group represented only 0.6% of the overall population, but accounted for 4.1% of all fractures and 9.3% of all orthopaedic trauma admissions. Patients in this group were more likely to require hospital admission (odds ratio 1.4), less likely to return to independent living (odds ratio 3.1), and to have a significantly longer hospital stay (ten days, p = 0.01). The 30- and 120-day unadjusted mortality was greater in the very elderly group. The 120-day mortality associated with non-hip fractures of the lower limb was equal to that of proximal femoral fractures, and was significantly increased with a delay to surgery > 48 hours for both age groups (p = 0.04). This suggests that the principle of early surgery and mobilisation of elderly patients with hip fractures should be extended to include all those in this vulnerable age group.
Peri-acetabular rotational osteotomy with concomitant hip arthroscopy for treatment of hip dysplasia
Authors: Kim K.-I. , Cho Y.-J. , Ramteke A. A. , Yoo M.-C. 
Published: May 2011

Reconstructive acetabular osteotomy is a well established and effective procedure in the treatment of acetabular dysplasia. However, the dysplasia is frequently accompanied by intra-articular pathology such as labral tears. We intended to determine whether a concomitant hip arthroscopy with peri-acetabular rotational osteotomy could identify and treat intra-articular pathology associated with dysplasia and thereby produce a favourable outcome. We prospectively evaluated 43 consecutive hips treated by combined arthroscopy and acetabular osteotomy. Intra-operative arthroscopic examination revealed labral lesions in 38 hips. At a mean follow-up of 74 months (60 to 97) the mean Harris hip score improved from 72.4 to 94.0 (p < 0.001), as did all the radiological parameters (p < 0.001). Complications included penetration of the joint by the osteotome in one patient, a fracture of the posterior column in another and deep-vein thrombosis in one further patient. This combined surgical treatment gave good results in the medium term. We suggest that arthroscopy of the hip can be performed in conjunction with peri-acetabular osteotomy to provide good results in patients with symptomatic dysplasia of the hip, and the arthroscopic treatment of intra-articular pathology may alter the progression of osteoarthritis.