bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corneal penetration of simultaneously applied topical levofloxacin, norfloxacin and lomefloxacin in human eyes
Authors: Yamada Masakazu , Ishikawa Kaoru , Mochizuki Hiroshi , Kawai Masataka 
Published: October 2005

Abstract.Purpose:  This study was performed to assess the corneal penetration of three topically applied fluoroquinolones (levofloxacin, norfloxacin and lomefloxacin) in corneal buttons obtained from patients undergoing penetrating keratoplasty. Methods:  Fourteen patients received three drops each of 0.5% levofloxacin, 0.3% norfloxacin and 0.3% lomefloxacin (the standard clinically available preparations) over a 30‐min interval beginning 90 mins before their scheduled keratoplasty. Corneal samples obtained from excised buttons at the time of surgery were stored at − 80 ° until analysis. The concentration of the administered fluoroquinolones was measured using high‐performance liquid chromatography. Results:  The mean corneal concentration of levofloxacin (4.6 ± 3.5 µg/g, mean ± standard deviation) was significantly higher than that of lomefloxacin (2.7 ± 1.8 µg/g, p = 0.0018) and norfloxacin (1.3 ± 1.2 µg/g, p = 0.00012). Conclusion:  Levofloxacin achieves a higher mean corneal concentration than norfloxacin and lomefloxacin in the human cornea.
Self‐assessed visual function for patients with posterior capsule opacification before and after capsulotomy
Authors: Sundelin Karin , Lundström Mats , Stenevi Ulf 
Published: October 2005

Abstract.Purpose:  To describe the functional outcome, as defined using the Catquest questionnaire, for patients with posterior capsule opacification (PCO) after capsulotomy. Methods:  A total of 47 patients with PCO were examined before and 1 month after capsulotomy. In addition to the ophthalmic examination, Catquest was completed and a digital image of the posterior lens capsule acquired. Results:  Capsulotomy resulted in a good level of benefit, as defined using Catquest, for 77% of the patients. No subgroup of patients who derived an exceedingly good or poor level of benefit was identified. Disabilities in daily life, satisfaction with vision and symptoms of glare improved from treatment (p < 0.001, p < 0.001 and p = 0.002, respectively). The results were comparable with the benefits of cataract surgery. Conclusions:  Self‐assessed visual function as defined using Catquest improved after capsulotomy for the vast majority of patients with PCO. No group of patients with exceptionally good or poor levels of benefit could be identified with certainty. However, the majority of those with a poor outcome were elderly individuals with ocular comorbidity. The overall functional results from treatment of PCO were very similar to those achieved after cataract surgery.
Computer‐based Training in der Dermatoonkologie – erste Ergebnisse zum Vergleich elektronischer Lernprogramme mit Präsenzlehre
Authors: Smolle Josef , Staber Reinhard , De Neges Hei , Reibnegger Gilbert , Kerl Helmut 
Published: October 2005

Zusammenfassung Hintergrund: Elektronische Medien spielen in der medizinischen Ausbildung eine zunehmende Rolle. Es stellt sich die Frage, wie Computerlernprogramme im Vergleich zu innovativen didaktischen Konzepten im Präsenzunterricht abschneiden. Methoden: An der Untersuchung nahmen 26 Studierende teil. In einem speziellen Studienmodul „Dermatoonkologie” im Rahmen eines integrierten medizinischen Curriculums wurde ein Teil des Stoffs in Form von Team‐Learning als Präsenzveranstaltung vermittelt, der andere Teil dagegen als Internet‐basiertes Computer‐based‐Training. Die Ergebnisse der nachfolgenden Multiple‐Choice‐Prüfung wurden in dieser Hinsicht statistisch ausgewertet. Ergebnisse: Die Prüfungsergebnisse waren bei jenen Fragen, die sich auf Computer‐based Trainings‐Inhalte bezogen, mit 90,4 ± 12,5 % richtigen Antworten signifikant besser als bei jenen, die sich aus dem Stoff des Team‐Learning rekrutiert hatten (80,6 ± 13,1 %; p < 0,001). Die Ergebnisse beider Prüfungsteile zeigten innerhalb der Einzelpersonen eine starke Korrelation (r = 0,52, p < 0,01), jedoch keinen statistischen Zusammenhang mit den übrigen Prüfungsleistungen der Studierenden. Schlussfolgerungen: Unser Beispiel aus der dermatoonkologischen Ausbildung zeigt, dass – soweit angesichts der unterschiedlichen Lerninhalte beurteilbar – Computer‐based Training einem innovativen Format der Präsenzlehre hinsichtlich der Prüfungsergebnisse überlegen sein kann.
Analysis of a Highly Flexible Conformational Immunogenic Domain A in Hepatitis C Virus E2
Authors: Keck Zhen-Yong , Li Ta-Kai , Xia Jinming , Bartosch Birke , Cosset François-Loïc , Dubuisson Jean , Foung Steven K. H. 
Published: October 2005

ABSTRACT

Hepatitis C (HCV) E2 glycoprotein is involved in virus attachment and entry, and its structural organization is largely unknown. Characterization of a panel of human monoclonal antibodies (HMAbs) to HCV by competition studies has led to an immunogenic organization model of E2 with three domains designated A, B, and C and epitopes in each domain having similar structural and functional properties. Domain A contains nonneutralizing epitopes, and domains B and C contain neutralizing epitopes. The isolation and characterization of three new HMAbs within domain A for a total of six provide support for this model. All six domain A HMAbs do not neutralize HCV retroviral pseudotype particle (HCVpp) infection on Huh-7 cells, and all six HMAbs have similar binding affinity and maximum binding,
B
max
, a relative indicator of epitope density, as other neutralizing HMAbs, suggesting that neutralization is epitope specific and not by binding to any surface epitope. The dose-dependent neutralizing activity of CBH-7, an HMAb to a domain C epitope in spatial proximity to domain A, and of CBH-5, a domain B HMAb to a more distant epitope, were tested in the presence and absence of each domain A HMAb. No enhancement or reduction in CBH-7 or CBH-5 neutralizing activity was observed, indicating that the potential induction of nonneutralizing antibodies should not be a central issue for HCV vaccine design. To assess whether domain A is involved in the structural changes as part of a pH-dependent virus envelope fusion process, changes in antibody binding patterns to normal pH and acid pH-treated HCVpp were measured. Antibody binding affinity of HMAbs to HCVpp was not affected by low pH. However, the
B
max
values for low-pH-treated HCVpp with antibodies to domain A increased 46%, for domain C (CBH-7) they increased 23%, and for domain B (CBH-5) there was a decrease of 12%. Collectively, the organization and function of HCV E2 antigenic domains are roughly analogous to the large envelope glycoprotein E organizational structure for other flaviviruses with three distinct structural and functional domains.
Worldwide Genomic Diversity of the High-Risk Human Papillomavirus Types 31, 35, 52, and 58, Four Close Relatives of Human Papillomavirus Type 16
Authors: Calleja-Macias Itzel E. , Villa Luisa L. , Prado Jose C. , Kalantari Mina , Allan Bruce , Williamson Anna-Lise , Chung Lap-Ping , Collins Robert J. , Zuna Rosemary E. , Dunn S. Terence , Chu Tang-Yuan , Cubie Heather A. , Cuschieri Kate , von Knebel-Doeberitz Magnus , Martins Claudia R. , Sanchez Gloria I. , Bosch F. Xavier , Munoz Nubia , Bernard Hans-Ulrich 
Published: October 2005

ABSTRACT
Among the more than one hundred formally described human papillomavirus (HPV) types, 18 are referred to as high-risk HPV types due to their association with anogenital cancer. Despite pathogenic similarities, these types form three remotely related taxonomic groups. One of these groups is called HPV species 9 and is formed by HPV-16, the most common and best-studied type, together with HPV-31, -33, -35, -52, -58, and -67. Previous worldwide comparisons of HPV-16 samples showed about 2% nucleotide diversity between isolates, which were subsequently termed variants. The distribution of divergent variants has been found to correlate frequently with the geographic origin and the ethnicity of the infected patients and led to the concept of unique African, European, Asian, and Native American HPV-16 variants. In the current study, we address the question of whether geography and ethnicity also correlate with sequence variations found for HPV-31, -35, -52, and -58. This was done by sequencing the long control region in samples derived from Europe, Asia, and Africa, and from immigrant populations in North and South America. We observed maximal divergence between any two variants within each of these four HPV types ranging from 1.8 to 3.6% based on nucleotide exchanges and, occasionally, on insertions and deletions. Similar to the case with HPV-16, these mutations are not random but indicate a relationship between the variants in form of phylogenetic trees. An interesting example is presented by a 16-bp insert in select variants of HPV-35, which appears to have given rise to additional variants by nucleotide exchanges within the insert. All trees showed distinct phylogenetic topologies, ranging from dichotomic branching in the case of HPV-31 to star phylogenies of the other three types. No clear similarities between these types or between these types and HPV-16 exist. While variant branches in some types were specific for Europe, Africa, or East Asia, none of the four trees reflected human evolution and spread to the extent illustrated by HPV-16. One possible explanation is that the rare HPV types that we studied spread and thereby diversified more slowly than the more abundant HPV-16 and may have established much of today's variant diversity already before the worldwide spread of humans 100,000 years ago. Most variants had prototypic amino acid sequences within the E6 oncoprotein and a segment of the L1 capsid protein. Some had one, two, or three amino acid substitutions in these regions, which might indicate biological and pathogenic diversity between the variants of each HPV type.
Consolidation In Pakistan's Retail Sector*
Authors: Ghani Jawaid Abdul 
Published: October 2005

This paper reviews changes which occurred over the last decade in the retail sector in urban Pakistan, in terms of a decrease in traditional ‘kiryana’ stores, an increase in general stores, and the emergence of new formats such as superstores, malls, and retail chains. These trends are discussed in the context of broader socio–economic changes, including growth in the urban middle class and disposable incomes. The paper discusses similar trends that occurred in the late nineteenth century in North America and Europe, the recent rise in international retailing, and the possibility of global retailers such as Germany's Metro and the French Carrefour, entering the Pakistani market. The entry of such firms has often resulted in profoundly altering the retail landscape, as has been the experience in the less developed markets of East Europe, Latin America, and the Asia Pacific region. It is estimated that in 2002, about 6.8 million of the 50 million people living in urban Pakistan belonged to the upper and upper–middle class, and represented a grocery market worth $1.7 billion. This segment, projected to grow to 17 million people by the year 2010, is expected to be the first to switch to modern retail stores. This paper projects the impact global retailers might have on Pakistan's retail landscape.
Arrested natural killer cell development associated with transgene insertion into the Atf2 locus
Authors: Kim Sungjin , Song Yun-Jeong , Higuchi Darryl A. , Kang Hyunseok P. , Pratt Jennifer R. , Yang Liping , Hong Caron M. , Poursine-Laurent Jennifer , Iizuka Koho , French Anthony R. , Sunwoo John B. , Ishii Shunsuke , Reimold Andreas M. , Yokoyama Wayne M. 
Published: October 2005

AbstractNatural killer (NK) cell development in the bone marrow is not fully understood. Following lineage commitment, these cells appear to advance through a series of developmental stages that are beginning to be characterized. We previously reported a selective deficiency of NK cells in a C57BL/6 mouse with a transgenic construct consisting of the cDNA for the Ly49A major histocompatibility complex (MHC) class 1–specific inhibitory receptor driven by the granzyme A gene. This mouse has few NK cells in peripheral tissues with relative preservation of other immune cells, including T and B cells. Herein we demonstrate that these mice have an accumulation of NK cells with an immature phenotype in the bone marrow, consistent with a block at a previously proposed stage in normal NK-cell development. The phenotype is associated with transgenic insertion into Atf2, the gene for the basic leucine zipper (bZIP) transcription factor family member ATF-2. Although analysis of Atf2-null NK cells shows no defect, the transgenic mice express abnormal truncated Atf2 transcripts that may mediate a repressor effect because ATF2 can heterodimerize with other bZIP molecules. The defect is cell intrinsic, suggesting that certain bZIP molecules play significant roles in NK-cell development.
Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study
Authors: Dahl Morten , Tybjærg-Hansen Anne , Lange Peter , Nordestgaard Børge G 
Published: October 2005

AbstractBackgroundCarriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD).MethodsWe genotyped 9131 individuals from the adult Danish population for cystic fibrosis 5T, 7T, 9T, and F508del alleles, and examined associations between 11 different genotype combinations, and annual FEV1decline and risk of asthma or COPD.Results5T heterozygotes vs. 7T homozygous controls had no increase in annual FEV1decline, self-reported asthma, spirometry-defined COPD, or incidence of hospitalization from asthma or COPD. In 5T/7T heterozygotes vs. 7T homozygous controls we had 90% power to detect an increase in FEV1decline of 8 ml, an odds ratio for self-reported asthma and spirometry-defined COPD of 1.9 and 1.7, and a hazard ratio for asthma and COPD hospitalization of 1.8 and 1.6, respectively. Both 5T homozygotes identified in the study showed evidence of asthma, while none of four 5T/F508del compound heterozygotes had severe pulmonary disease. 7T/9T individuals had annual decline in FEV1of 19 ml compared with 21 ml in 7T homozygous controls (t-test:P = 0.03). 6.7% of 7T homozygotes without an F508del allele in thecystic fibrosis transmembrane conductance regulatorgene reported asthma vs. 11% of 7T/9T individuals with an F508del allele (χ2:P = 0.01) and 40% of 7T homozygotes with an F508del allele (P = 0.04). 7T homozygotes with vs. without an F508del allele also had higher incidence of asthma hospitalization (log-rank:P = 0.003); unadjusted and adjusted equivalent hazard ratios for asthma hospitalization were 11 (95%CI:1.5–78) and 6.3 (0.84–47) in 7T homozygotes with vs. without an F508del allele.ConclusionPolythymidine 5T heterozygosity is not associated with pulmonary dysfunction or disease in the adult Caucasian population. Furthermore, our results support that F508del heterozygosity is associated with increased asthma risk independently of the 5T allele.
Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells
Authors: Bossios Apostolos , Psarras Stelios , Gourgiotis Dimitrios , Skevaki Chrysanthi L , Constantopoulos Andreas G , Saxoni-Papageorgiou Photini , Papadopoulos Nikolaos G 
Published: October 2005

Abstract

Background
Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro.

Methods
Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA) by flow cytometry.

Results
RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation.

Conclusion
RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.
The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]
Authors: Kulik Alexander , Le May Michel , Wells George A , Mesana Thierry G , Ruel Marc 
Published: October 2005

Abstract

Background
Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery.

Methods
Patients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery.

Discussion
This trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients.
Randomized phase II – study evaluating EGFR targeting therapy with Cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer – PARC: study protocol [ISRCTN56652283]
Authors: Krempien R , Muenter MW , Huber PE , Nill S , Friess H , Timke C , Didinger B , Buechler P , Heeger S , Herfarth KK , Abdollahi A , Buchler MW , Debus J 
Published: October 2005

Abstract

Background
Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR.

Methods/design
The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrolment.

Discussion
The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment).
Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life.
Unfavourable birth outcomes of the Roma women in the Czech Republic and the potential explanations: a population-based study
Authors: Bobak Martin , Dejmek Jan , Solansky Ivo , Sram Radim J 
Published: October 2005

Abstract

Background
Data on the health status of the Roma people in Central and Eastern Europe are sparse and the reasons for their poor health are not clear. The objective of this study was to quantify the differences in birth outcomes between Roma and non-Roma mothers in the Czech Republic and to investigate the potential causes of such differences.

Method
A population-based study recruited 8938 non-Roma and 1388 Roma hospitalised singleton births that occurred in two Czech districts (Teplice and Prachatice) between 1995 and 2004. During their stay in hospital, mothers completed a questionnaire on their demographic and socioeconomic characteristics and maternal smoking and alcohol consumption. Data on maternal height and weight and on infants' birth weight and gestational age were taken from hospital records.

Results
Birth weight and gestational age of Roma infants was 373 (SE 15) g and 0.92 (0.05) weeks, respectively, lower than in non-Roma infants. Controlling for demographic, socioeconomic and behavioural factors reduced these differences to 133 (18) g and 0.57 (0.06) weeks, respectively (all p-values < 0.001). In terms of binary outcomes, the Roma vs. non-Roma odds ratios were 4.5 (95% CI 3.7–5.4) for low birth weight (< 2500 g), 2.8 (2.2–3.4) for preterm birth (< 37 weeks of gestation), and 2.9 (2.5–3.4) for intrauterine grown retardation (<10th percentile of birth weight for gestational age); controlling for all covariates reduced these odds ratios to 1.7 (1.3–2.2), 1.5 (1.1–2.0) and 1.3 (1.0–1.6), respectively. Maternal education made the largest contribution to the ethnic differences; the role of health behaviours was relatively modest.

Conclusion
There are striking differences in birth outcomes between Roma and non-Roma mothers. The causes of these differences are complex but largely socioeconomic.