bluuebunny/crossref_metadata_2025 huggingface dataset:
An experimental study of a facade mounted light pipe
Authors: Duc Hien V. , Chirarattananon S.
Published: May 2009

An experimental study of a rectangular light pipe mounted on a façade is reported. We used static and adjustable reflectors for enhancing capture and transmission of sunlight through the light pipe. A ray tracing technique was used to calculate the direct sunlight reflected into the light pipe and its transmission to the end of the light pipe. An inter-reflection method was used to calculate the transmission of diffuse skylight and the resulting daylight illuminance in the building interior. The experimental and calculation results demonstrate that daylighting through light pipes can provide acceptable illuminances in deep spaces for almost the whole day under conditions of clear and partly cloudy skies.
A colour harmony rendering index based on predictions of colour harmony impression
Authors: Szabó F. , Bodrogi P. , Schanda J.
Published: May 2009

This study describes the development of a new measure intended to improve the description of light source colour quality. Previously, the authors have developed several colour harmony formulae to describe observers' impressions of colour harmony for two- and three-colour combinations seen under well-defined viewing conditions. One of the applications of these formulae is to quantify the distortion of colour harmony that can occur on changing from one light source to another. Based on the colour harmony predictions of these formulae for a sample set of colours seen under reference and test light sources a new light source colour quality metric, the `colour harmony rendering index', is defined. Two experiments were carried out to investigate the correlation between visual observations and this new colour quality metric.
Retention of School-Based SLPs: Relationships Among Caseload Size, Workload Satisfaction, Job Satisfaction, and Best Practice
Authors: Hutchins Tiffany L. , Howard Malinda , Prelock Patricia A. , Belin Gayle
Published: May 2009

Nationally, the shortage of speech-language pathologists (SLPs) in the schools is growing. As such, it is important to understand factors related to the retention of SLPs in this setting. This study expanded on previous research by examining a wider range of factors that may be related to the retention of SLPs including caseload size, workload satisfaction, job satisfaction, and time available to conduct best practice. Participants were 75 full-time SLPs working in a school setting in the state of Vermont who completed a survey designed to solicit information concerning the variables of interest. Several dimensions of job satisfaction and best practice predicted retention, caseload, and especially workload. The results also suggested that high workloads complicate the implementation of best practice and have implications for retention. Limitations of the research and implications for practice are discussed.
Cascading crises, resilience and social support within the onset and development of multiple chronic conditions
Authors: Sells Dave , Sledge William H. , Wieland Melissa , Walden David , Flanagan Elizabeth , Miller Rebecca , Davidson Larry
Published: May 2009

Objective: To describe and better understand adults' responses to the onset, accrual and influence of multiple chronic conditions and to social support in adapting to consequent difficulties.

Methods: Qualitative study of 33 adults with multiple chronic illnesses randomly sampled from an urban primary care clinic. Semi-structured interviews targeted retrospective accounts of illness onset, consequent loss, as well as current accounts of social support and adaptation. All interviews were audio-recorded, professionally transcribed and analysed according to established phenomenological procedures.

Results: Participants' responses revealed illness onset as a virtual cascade of medical, emotional and social hardships, leading to loss and subsequent adaptation through personal resilience and particularly, available social support. Participants also described patterns of adaptation punctuated by the felt need and rewards of providing care to others.

Discussion: The experience of multiple chronic illnesses has a distinct pattern of development and consequence, involving challenges to personal identity and the benefits of social support from and to others. Our results suggest that programmes addressing the needs of persons with multiple chronic conditions might tailor interventions in ways that maximally address their unique challenges.
The lived experience of hope among parents of a child with Duchenne muscular dystrophy: perceiving the human being beyond the illness
Authors: Samson André , Tomiak E. , Dimillo J. , Lavigne R. , Miles S. , Choquette M. , Chakraborty P. , Jacob P.
Published: May 2009

Objectives: Duchenne muscular dystrophy (DMD) is genetically determined, progressive and incurable. Our study's primary objective was to describe the lived experience of hope among parents of a child with DMD.

Methods: Semi-structured interviews were conducted with 12 parents having a child with DMD. A qualitative/ phenomenological approach was utilized to analyse the essential aspects of this experience.

Results: We show that the experience of parental hope emerges from the cognitive appraisal of DMD. The child's illness can be perceived in three ways: as a severe loss, a call to adapt or a way to rediscover the child. Each of these appraisals leads to different ways of hoping. Parents can hope for a cure, the child's well-being or to see their child becoming a whole person. Hope can help parents absorb the initial crisis, sustain their adaptation or prepare for the fatal outcome.

Discussion: Previous research has demonstrated that cognitive appraisal plays a central role in psychosocial adaptation to illness. Our research indicates that perception can also shape the nature of hope and suggests that health professionals should pay particular attention to the nature of parental hope. The fabric of parental hope can give an indication of how parents are coping and adjusting.
Future directions for investigation of fatigue in chronic hepatitis C viral infection
Authors: Seaman Kenneth , Paterson Barbara L. , Vallis Michael , Hirsch Geri , Peltekian Kevork M.
Published: May 2009

Fatigue is a common and often debilitating symptom for people living with chronic hepatitis C viral infection. Numerous published reports in the past decade have attempted to address the nature and aetiology of fatigue in chronic hepatitis C; however, this field is plagued with lack of clarity about how hepatitis C virus (HCV)-related fatigue occurs and when it is experienced by the infected person. Consequently, both patients and clinicians alike are unclear about how to mediate or prevent the negative consequences of HCV-related fatigue. In the following article, the authors identify areas of ambiguity and incongruity that have evolved primarily from the underlying assumptions and methodological decisions of researchers in the field of HCV-related fatigue. Research related to fatigue in chronic illness is drawn upon to suggest future directions for investigations and interventions in the field of HCV-related fatigue. Future research needs to move beyond the subjective symptomatology of HCV-related fatigue and begin to account for the multidimensional and contextualised nature of the fatigue experience.
Rapid pulmonary fibrosis induced by acute lung injury via a lipopolysaccharide three-hit regimen
Authors: Hui Li  , Shaohui Du  , Lina Yang  , Yangyan Chen  , Wei Huang  , Rong Zhang  , Yinghai Cui  , Jun Yang  , Dongfeng Chen  , Yiwei Li  , Saixia Zhang  , Jianhong Zhou  , Zhijun Wei  , Zhibin Yao
Published: May 2009

Based on the common characteristic of severe acute respiratory syndrome (SARS) and highly pathogenic avian influenza and the mechanism of inflammation and fibrosis, it is speculated that there should exist a fundamental pathological rule that severe acute lung injury (ALI)-induced rapid pulmonary fibrosis is caused by various etiological factors, such as SARS coronavirus, H5N1-virus, or other unknown factors, and also by lipopolysaccharide (LPS), the most common etiological factor. The investigation employed intratracheally, and intraperitoneally and intratracheally applied LPS three-hit regimen, compared with bleomycin-induced chronic pulmonary fibrosis. Inflammatory damage and fibrosis were evaluated, and the molecular mechanism was analyzed according to Th1/Th2 balance, Sma- and MAD-related proteins (Smads) and signal transducer and activator of transcriptions (STATs) expression. The results suggested that rapid pulmonary fibrosis could be induced by ALI via LPS three-hits. The period from 3—7 days in the LPS group was the first rapid pulmonary fibrosis stage, whereas the second fast fibrosis stage occurred on days 14—21. Th2 cell polarization, Smad4 and Smad7 should be the crucial molecular mechanism of ALI-induced rapid fibrosis. The investigation was not only performed to establish a new rapid pulmonary fibrosis model, but also to provide the elicitation for mechanism of ALI changed into the rapid pulmonary fibrosis.
Activation of Toll-like receptors 2 and 4 in Aspergillus fumigatus keratitis
Authors: Jie Zhao  , Wu Xin-yi , Yu Fu-Shin X.
Published: May 2009

Toll-like receptor (TLR) 2 and TLR4 are major receptors of Aspergillus fumigatus. Aspergillus fumigatus signaling in cornea induces the production of many pro-inflammatory molecules. In this study, we have shown that exposure of telomerase-immortalized human corneal epithelial cells (HCECs) to A. fumigatus antigens resulted in up-regulation of TLR2 and TLR4, and release of IL-1β and IL-10 in HCECs, effects that could be inhibited by treatment with TLR2, and TLR4 antibodies. In addition, the A. fumigatus antigens-induced production of IL-1β and IL-10 in supernatants of corneal epithelial cells was also attenuated by NF-κB inhibitor. Aspergillus fumigatus keratitis developed in Wistar rats, as evidenced by high SLE scores, influx of polymorphonuclear leukocytes (PMNs), activation of TLR2 and TLR4, and production of IL-1β and IL-10 over controls. These findings indicate that the cornea has functional TLR2 and TLR4, and activation of TLR2 and TLR4 through NF-κB may contribute to pathogenesis of keratomycosis.
Review: Immunity mechanisms in crustaceans
Authors: Vazquez Lorena , Alpuche Juan , Maldonado Guadalupe , Agundis Concepción , Pereyra-Morales Ali , Zenteno Edgar
Published: May 2009

Crustacean aquaculture represents a major industry in tropical developing countries. As a result of high culture densities and increasing extension of aquaculture farms, the presence of diseases has also increased, inducing economic losses. Invertebrates, which lack adaptive immune systems, have developed defense systems that respond against antigens on the surface of potential pathogens. The defense mechanisms of crustaceans depend completely on the innate immune system that is activated when pathogen-associated molecular patterns are recognized by soluble or by cell surface host proteins, such as lectins, antimicrobial, clotting, and pattern recognition proteins, which, in turn, activate cellular or humoral effector mechanisms to destroy invading pathogens. This work is aimed at presenting the main characteristics of the crustacean proteins that participate in immune defense by specific recognition of carbohydrate containing molecules, i.e. glycans, glycolipids, glycoproteins, peptidoglycans, or lipopolysaccharides from Gram-negative and Gram-positive bacteria, viruses, or fungi. We review some basic aspects of crustacean effector defense processes, like agglutination, encapsulation, phagocytosis, clottable proteins, and bactericidal activity, induced by these carbohydrate-driven recognition patterns.
Immunotherapy: rAAV2 expressing interleukin-15 inhibits HeLa cell tumor growth in mice
Authors: Yiang Giou-Teng , Harn Horng-Jyh , Yu Yung-Luen , Hu Sheng-Chuan , Hung Yu-Ting , Hsieh Chia-Jung , Lin Shinn-Zong , Wei Chyou-Wei
Published: May 2009

Human interleukin-15 (hIL15) has anti-tumor activities, but it is not convenient for tumor treatment because of its short half-life. A gene therapy for mouse lung cancer using an adenovirus vector expressing IL15 has been reported. However, adenovirus vector-mediated gene therapy can provoke cellular toxicity and inflammatory reactions. The recombinant adenovirus-associated vector 2 (rAAV2) is safer due to minimal cellular toxicity and immune response. In order to demonstrate that gene therapy can be used safely and successfully for human cancer treatment, the rAAV2 expressing hIL15 gene (rAAV2-hIL15) is applied for human cervical cancer, HeLa cell, in this study. This study successfully demonstrates that rAAV2-hIL15 can express IL15 with bioactivities in vitro and in vivo. In conclusion, our studies show that human cervical cancers are inhibited on animal model with rAAV2-hIL15 treatment and provide a safer and important reference for human cancer gene therapy.
Evaluation of methods for amplification of picogram amounts of total RNA for whole genome expression profiling
Authors: Clément-Ziza Mathieu , Gentien David , Lyonnet Stanislas , Thiery Jean-Paul , Besmond Claude , Decraene Charles
Published: May 2009

Background

For more than a decade, microarrays have been a powerful and widely used tool to explore the transcriptome of biological systems. However, the amount of biological material from cell sorting or laser capture microdissection is much too small to perform microarray studies. To address this issue, RNA amplification methods have been developed to generate sufficient targets from picogram amounts of total RNA to perform microarray hybridisation.

Results

In this study, four commercial protocols for amplification of picograms amounts of input RNA for microarray expression profiling were evaluated and compared. The quantitative and qualitative performances of the methods were assessed. Microarrays were hybridised with the amplified targets and the amplification protocols were compared with respect to the quality of expression profiles, reproducibility within a concentration range of input RNA, and sensitivity. The results demonstrate significant differences between these four methods.

Conclusion

In our hands, the WT-Ovation pico system proposed by Nugen appears to be the most suitable for RNA amplification. This comparative study will be useful to scientists needing to choose an amplification method to carry out microarray experiments involving samples comprising only a few cells and generating picogram amounts of RNA.
Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism
Authors: Stathopoulou Panagiota G , Galicia Johnah C , Benakanakere Manjunatha R , Garcia Carlos A , Potempa Jan , Kinane Denis F
Published: May 2009

Background

The oral pathogen Porphyromonas gingivalis has been shown to modulate apoptosis in different cell types, but its effect on epithelial cells remains unclear.

Results

We demonstrate that primary human gingival epithelial cells (HGECs) challenged with live P. gingivalis for 24 hours exhibit apoptosis, and we characterize this by M30 epitope detection, caspase-3 activity, DNA fragmentation and Annexin-V staining. Live bacteria strongly upregulated intrinsic and extrinsic apoptotic pathways. Pro-apoptotic molecules such as caspase-3, -8, -9, Bid and Bax were upregulated after 24 hours. The anti-apoptotic Bcl-2 was also upregulated, but this was not sufficient to ensure cell survival. The main P. gingivalis proteases arginine and lysine gingipains are necessary and sufficient to induce host cell apoptosis. Thus, live P. gingivalis can invoke gingival epithelial cell apoptosis in a time and dose dependent manner with significant apoptosis occurring between 12 and 24 hours of challenge via a gingipain-dependent mechanism.

Conclusion

The present study provides evidence that live, but not heat-killed, P. gingivalis can induce apoptosis after 24 hours of challenge in primary human gingival epithelial cells. Either arginine or lysine gingipains are necessary and sufficient factors in P. gingivalis elicited apoptosis.
Systematic cloning and analysis of autophagy-related genes from the silkworm Bombyx mori
Authors: Zhang Xuan , Hu Zhan-Ying , Li Wei-Fang , Li Qing-Rong , Deng Xiao-Juan , Yang Wan-Ying , Cao Yang , Zhou Cong-Zhao
Published: May 2009

Background

Through the whole life of eukaryotes, autophagy plays an important role in various biological events including development, differentiation and determination of lifespan. A full set of genes and their encoded proteins of this evolutionarily conserved pathway have been identified in many eukaryotic organisms from yeast to mammals. However, this pathway in the insect model organism, the silkworm Bombyx mori, remains poorly investigated.

Results

Based on the autophagy pathway in several model organisms and a series of bioinformatic analyses, we have found more than 20 autophagy-related genes from the current database of the silkworm Bombyx mori. These genes could be further classified into the signal transduction pathway and two ubiquitin-like pathways. Using the mRNA extracted from the silkgland, we cloned the full length cDNA fragments of some key genes via reverse transcription PCR and 3' rapid amplification of cDNA ends (RACE). In addition, we found that the transcription levels of two indicator genes BmATG8 and BmATG12 in the silkgland tend to be increased from 1st to 8th day of the fifth instar larvae.

Conclusion

Bioinformatics in combination with RT-PCR enable us to remodel a preliminary pathway of autophagy in the silkworm. Amplification and cloning of most autophagy-related genes from the silkgland indicated autophagy is indeed an activated process. Furthermore, the time-course transcriptional profiles of BmATG8 and BmATG12 revealed that both genes are up-regulated along the maturation of the silkgland during the fifth instar. These findings suggest that the autophagy should play an important role in Bombyx mori silkgland.
Cost of dengue and other febrile illnesses to households in rural Cambodia: a prospective community-based case-control study
Authors: Huy Rekol , Wichmann Ole , Beatty Mark , Ngan Chantha , Duong Socheat , Margolis Harold S , Vong Sirenda
Published: May 2009

Background

The average annual reported dengue incidence in Cambodia is 3.3/1,000 among children < 15 years of age (2002–2007). To estimate the economic burden of dengue, accurate cost-of-illness data are essential. We conducted a prospective, community-based, matched case-control study to assess the cost and impact of an episode of dengue fever and other febrile illness on households in rural Cambodia.

Methods

In 2006, active fever surveillance was conducted among a cohort of 6,694 children aged ≤ 15 years in 16 villages in Kampong Cham province, Cambodia. Subsequently, a case-control study was performed by individually assigning one non-dengue febrile control from the cohort to each laboratory-confirmed dengue case. Parents of cases and controls were interviewed using a standardized questionnaire to determine household-level, illness-related expenditures for medical and non-medical costs, and estimated income loss (see Additional file 1). The household socio-economic status was determined and its possible association with health seeking behaviour and the ability to pay for the costs of a febrile illness.

Results

Between September and November 2006, a total of 60 household heads were interviewed: 30 with dengue-positive and 30 with dengue-negative febrile children. Mean total dengue-related costs did not differ from those of other febrile illnesses (31.5 vs. 27.2 US$, p = 0.44). Hospitalization almost tripled the costs of dengue (from 14.3 to 40.1 US$) and doubled the costs of other febrile illnesses (from 17.0 to 36.2 US$). To finance the cost of a febrile illness, 67% of households incurred an average debt of 23.5 US$ and higher debt was associated with hospitalization compared to outpatient treatment (US$ 23.1 vs. US$ 4.5, p < 0.001). These costs compared to an average one-week expenditure on food of US$ 9.5 per household (range 2.5–21.3). In multivariate analysis, higher socio-economic status (odds ratio [OR] 4.4; 95% confidence interval [CI] 1.4–13.2), duration of fever (OR 2.1; 95%CI 1.3–3.5), and age (OR 0.8; 95%CI 0.7–0.9) were independently associated with hospitalization.

Conclusion

In Cambodia, dengue and other febrile illnesses pose a financial burden to households. A possible reason for a lower rate of hospitalization among children from poor households could be the burden of higher illness-related costs and debts.
Scientific writing: a randomized controlled trial comparing standard and on-line instruction
Authors: Phadtare Amruta , Bahmani Anu , Shah Anand , Pietrobon Ricardo
Published: May 2009

Background

Writing plays a central role in the communication of scientific ideas and is therefore a key aspect in researcher education, ultimately determining the success and long-term sustainability of their careers. Despite the growing popularity of e-learning, we are not aware of any existing study comparing on-line vs. traditional classroom-based methods for teaching scientific writing.

Methods

Forty eight participants from a medical, nursing and physiotherapy background from US and Brazil were randomly assigned to two groups (n = 24 per group): An on-line writing workshop group (on-line group), in which participants used virtual communication, google docs and standard writing templates, and a standard writing guidance training (standard group) where participants received standard instruction without the aid of virtual communication and writing templates. Two outcomes, manuscript quality was assessed using the scores obtained in Six subgroup analysis scale as the primary outcome measure, and satisfaction scores with Likert scale were evaluated. To control for observer variability, inter-observer reliability was assessed using Fleiss's kappa. A post-hoc analysis comparing rates of communication between mentors and participants was performed. Nonparametric tests were used to assess intervention efficacy.

Results

Excellent inter-observer reliability among three reviewers was found, with an Intraclass Correlation Coefficient (ICC) agreement = 0.931882 and ICC consistency = 0.932485. On-line group had better overall manuscript quality (p = 0.0017, SSQSavg score 75.3 ± 14.21, ranging from 37 to 94) compared to the standard group (47.27 ± 14.64, ranging from 20 to 72). Participant satisfaction was higher in the on-line group (4.3 ± 0.73) compared to the standard group (3.09 ± 1.11) (p = 0.001). The standard group also had fewer communication events compared to the on-line group (0.91 ± 0.81 vs. 2.05 ± 1.23; p = 0.0219).

Conclusion

Our protocol for on-line scientific writing instruction is better than standard face-to-face instruction in terms of writing quality and student satisfaction. Future studies should evaluate the protocol efficacy in larger longitudinal cohorts involving participants from different languages.
Pharmacokinetics, tissue distribution and mass balance of radiolabeled dihydroartemisinin in male rats
Authors: Xie Lisa H , Li Qigui , Zhang Jing , Weina Peter J
Published: May 2009

Background

Dihydroartemisinin (DHA), a powerful anti-malarial drug, has been used as monotherapy and artemisinin-based combination therapy (ACT) for more than decades. So far, however, the tissue distribution and metabolic profile of DHA data are not available from animal and humans.

Methods

Pharmacokinetics, tissue distribution, mass balance, and elimination of [14C] DHA have been studieded in rats following a single intravenous administration. Protein binding was performed with rat and human plasma. Drug concentrations were obtained up to 192 hr from measurements of total radioactivity and drug concentration to determine the contribution by the parent and metabolites to the total dose of drug injected from whole blood, plasma, urine and faecal samples.

Results

Drug was widely distributed after 1 hr and rapidly declined at 24 hr in all tissues except spleen until 96 hrs. Only 0.81% of the total radioactivity was detected in rat brain tissue. DHA revealed a high binding capacity with both rat and human plasma proteins (76–82%). The concentration of total radioactivity in the plasma fraction was less than 25% of that in blood total. Metabolism of DHA was observed with high excretion via bile into intestines and approximately 89–95% dose of all conjugations were accounted for in blood, urine and faeces. However, the majority of elimination of [14C] DHA was through urinary excretion (52% dose). The mean terminal half-lives of plasma and blood radioactivity (75.57–122.13 h) were significantly prolonged compared with that of unchanged DHA (1.03 h).

Conclusion

In rat brain, the total concentration of [14C] was 2-fold higher than that in plasma, indicating the radioactivity could easily penetrate the brain-blood barrier. Total radioactivity distributed in RBC was about three- to four-fold higher than that in plasma, suggesting that the powerful anti-malarial potency of DHA in the treatment of blood stage malaria may relate to the high RBC binding. Biliary excretion and multiple concentration peaks of DHA have been demonstrated with high urinary excretion due to a most likely drug re-absorption in the intestines (enterohepatic circulation). The long lasting metabolites of DHA (> 192 hr) in the rats may be also related to the enterohepatic circulation.
Tissue expression of Squamous Cellular Carcinoma Antigen (SCCA) is inversely correlated to tumor size in HCC
Authors: Trerotoli Paolo , Fransvea Emilia , Angelotti Umberto , Antonaci Giovanni , Lupo Luigi , Mazzocca Antonio , Mangia Anita , Antonaci Salvatore , Giannelli Gianluigi
Published: May 2009

Background

This study aimed to investigate squamous cellular carcinoma antigen (SCCA) in serum and in tumoral and paired peritumoral tissues. We studied 27 patients with liver cirrhosis (LC) and 55 with HCC: 20 with a single nodule < 3 cm (s-HCC) and 35 with a single nodule > 3 cm or multifocal (l-HCC).

Methods

Serum SCCA was measured by the ELISA kit, and in frozen tissues by immunohistochemistry, quantified with appropriate imaging analysis software and expressed in square microns. Continuous variables are reported as means and 95% confidence intervals. Comparisons between independent groups were performed with a generalized linear model and Tukey grouping. Pearson's correlation coefficients were determined to evaluate relations between markers. Qualitative variables were summarized as count and percentage. Statistical significance was set at p-value < 0.05.

Results

Serum SCCA values in LC patients were 0.41 (0.31–0.55) ng/ml and statistically different from both HCC groups: 1.6 (1.0–2.6) ng/ml in s-HCC, 2.2 (1.28–2.74) ng/ml in l-HCC. SCCA in hepatic tissue was 263.8 (176.6–394.01) μm2 in LC patients, statistically different from values in s-HCC: 1163.2 (863.6–1566.8) μm2 and l-HCC: 625.8 (534.5–732.6). All pairwise comparisons between groups yielded statistically significant differences. Tumoral SCCA resulted linearly related with nodule size, showing a statistically significant inverse relation between the two variables (b = -0.099, p = 0.024).

Conclusion

There was no statistically significant correlation between tissue and serum levels of SCCA. The significantly stronger expression of SCCA in smaller compared to larger HCC could be important for early HCC detection. However, the increased expression in peritumoral tissue could affect the significance of serological detection.
Doppler ultrasonography and exercise testing in diagnosing a popliteal artery adventitial cyst
Authors: Taurino Maurizio , Rizzo Luigi , Stella Nazzareno , Mastroddi Massimo , Conteduca Fabio , Maggiore Claudia , Faraglia Vittorio
Published: May 2009

We describe popliteal arterial adventitial cystic disease which causes intermittent claudication in a young athletic man, with atypical manifestation, without loss of foot pulses on knee flexion nor murmur in the popliteal fossa. The findings obtained from Magnetic Resonance Imaging were non-diagnostic. The diagnosis resulted from Echo-Doppler ultrasonography along with peak exercise testing. Ultrasonography also provided useful physiopathological informations suggesting that a popliteal artery adventitial cyst can become symptomatic if muscle exertion increases fluid pressure within the cyst, enough to cause hemodynamically significant endoluminal stenosis. Rapid diagnosis is essential to prevent progressive claudication threatening limb viability. To guarantee this professional sportsman a reliable and durable outcome, instead of less aggressive management, we resected the involved arterial segment and interposed an autologous saphenous-vein graft.
Role of TRPV3 in immune response to development of dermatitis
Authors: Imura Kinichi , Yoshioka Takeshi , Hirasawa Tsutomu , Sakata Tsuneaki
Published: May 2009

Background

Recently, it has been reported that the Gly573Ser substitution of transient receptor potential V3 (TRPV3) leads to increased ion-channel activity in keratinocytes. Our previous studies have indicated that the spontaneous hairless and dermatitis phenotypes of DS-Nh mice, which were newly established as an animal model of atopic dermatitis (AD), are caused by TRPV3Gly573Ser. Although this substitution causes hairlessness in several kinds of rodents, in our investigations, dermatitis developed in only a few animals. Here, we generated NC/Nga-Nh mice to elucidate the role of TRPV3Gly573Ser in NC/Nga mice, which is one of the most studied animal models of AD.

Methods

To establish and validate the new AD animal model, NC/Nga-Nh mice were generated using NC/Nga and DS-Nh mice, and their clinical features were compared. Next, T-cell receptor (TCR) Vβ usage in splenocytes, evaluation of bacterial colonization, and serological and histological analyses were carried out. Finally, repeated-hapten-application dermatitis was induced in these mice.

Results

NC/Nga-Nh mice did not develop spontaneous dermatitis, whereas DS-Nh mice displayed this phenotype when maintained under the same conditions. Serological analysis indicated that there really was a phenotypic difference between these mice, and TCR repertoire analysis indicated that TCRVβ haplotypes played an important role in the development of dermatitis. Artificial dermatitis developed in DS and NC/Nga-Nh mice, but not in DS-Nh and NC/Nga mice. Histological and serological analyses indicated that mouse strains were listed in descending order of number of skin mast cells: DS-Nh > DS ≈ NC/Nga-Nh > NC/Nga, and serum IgE levels were increased after 2,4,6 trinitrochlorobenzene application in these mice. Serum IgE level in DS-Nh mice was lower than that mesured in other strains.

Conclusion

Our results confirm the contribution of the TRPV3Gly573Ser gene to the development of repeated hapten dermatitis, but not spontaneous dermatitis in NC/Nga mice.
Treatment of multicentric Castleman's Disease accompanying multiple myeloma with bortezomib: a case report
Authors: Yuan Zhen-gang , Dun Xiao-yi , Li Yong-hua , Hou Jian
Published: May 2009

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder of unknown etiology and characterized by various clinical manifestations and multiple organ involvement. It has been reported in association with POEMS syndrome and can progress to Kaposi's sarcoma or malignant lymphoma. The disease runs a more aggressive course and a poor prognosis. Optimal therapies have not been well established up to now. We here reported a case of rare MCD complicated with multiple myeloma who received bortezomib and achieved very good remission. To our knowledge, this is the first report on MCD in the setting of multiple myeloma with good response to bortezomib.
Topoisomerase IIα Amplification Does Not Predict Benefit From Dose-Intense Cyclophosphamide, Doxorubicin, and Fluorouracil Therapy in HER2-Amplified Early Breast Cancer: Results of CALGB 8541/150013
Authors: Harris Lyndsay N. , Broadwater Gloria , Abu-Khalaf Maysa , Cowan David , Thor Ann D. , Budman Daniel , Cirrincione Constance T. , Berry Donald A. , Winer Eric P. , Hudis Clifford A. , Hayes Daniel F. , Friedman Paula , Ellis Matthew , Dressler Lynn
Published: May 2009

Purpose

We have demonstrated that patients with HER2-amplified tumors derive more benefit from higher doses of doxorubicin-containing chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil [CAF]). Because topoisomerase IIα (Topo-IIα) is a target for doxorubicin and is coamplified in 20% to 50% of HER2-amplified tumors, we postulated that Topo-IIα copy number might account for the benefit from CAF dose escalation in HER2-positive tumors. To address this hypothesis, we examined Topo-IIα and HER2 copy number, CAF dose, and clinical outcomes in Cancer and Leukemia Group B (CALGB) 8541.

Patients and Methods

Topo-IIα and HER2 copy number were measured by fluorescent in situ hybridization (FISH) using a triple-probe system, which includes Topo-IIα, HER2, and chromosome 17 (CEP17). Topo-IIα and/or HER2 were classified as amplified (≥ two copies/CEP17, deleted (≤ 0.67 copies/CEP17) and normal copy number (> .67 to < 2.0 copies/CEP17).

Results

Topo-IIα/HER2/CEP17 measurement was successful in 624 of 687 cases. HER2 was amplified in 117 cases (19%). Topo-IIα was amplified in 41 cases (7%) and deleted in 69 cases (11%). Topo-IIα amplification was highly correlated with HER2 amplification (39 of 41; P < .0001), HER2 by immunohistochemistry, and by dual-probe FISH. Topo-IIα was deleted in both the HER2-amplified (30 of 69; 43%), normal (22 of 69; 32%) and HER2-deleted tumors (17 of 69; 25%). Although Topo-IIα–amplified tumors were nearly always HER2 amplified, these tumors did not receive benefit from increasing the dose of CAF (P = .15).

Conclusion

The correlative companion study CALGB 8541-150013 does not support the hypothesis that Topo-IIα amplification is the mechanism behind benefit from increased dose of anthracyclines in HER2-positive breast cancer.
ATR Mutation in Endometrioid Endometrial Cancer Is Associated With Poor Clinical Outcomes
Authors: Zighelboim Israel , Schmidt Amy P. , Gao Feng , Thaker Premal H. , Powell Matthew A. , Rader Janet S. , Gibb Randall K. , Mutch David G. , Goodfellow Paul J.
Published: May 2009

Purpose

Mutations in the DNA damage response gene ATR (exon 10 A10 mononucleotide repeat) have been previously described in endometrial and other cancers with defective DNA mismatch repair. In vitro studies showed that endometrial cancer cell lines with A10 repeat tract truncating mutations have a failure in the ATR-dependent DNA damage response. Cell lines carrying A10 mutations fail to trigger Chk1 activation in response to ionizing radiation and topoisomerase inhibitors. We sought to determine the frequency and clinicopathologic significance of ATR mutations in patients with endometrioid endometrial cancer.

Patients and Methods

The ATR exon 10 A10 repeat was analyzed by direct sequencing in 141 tumors with microsatellite instability (MSI-positive) and 107 microsatellite stable (MSI-negative) tumors. The relationships between mutations and clinicopathologic variables, including overall and disease-free survival, were assessed using contingency table tests and Cox proportional hazard models.

Results

ATR mutations were identified in 12 cases (4.8%; three cases with insertions and nine cases with deletions). Mutations occurred exclusively in MSI-positive tumors (P = .02), with an overall mutation rate of 8.5%. Mutation was not associated with age, race, surgical stage, International Federation of Gynecology and Obstetrics grade, or adjuvant treatment. Multivariate analyses revealed a significant association with reduced overall survival (hazard ratio [HR] = 3.88; 95% CI, 1.64 to 9.18; P = .002) and disease-free survival (HR = 4.29; 95% CI, 1.48 to 12.45; P = .007).

Conclusion

Truncating ATR mutations in endometrial cancers are associated with biologic aggressiveness as evidenced by reduced disease-free and overall survival. Knowledge of ATR mutation status may hold promise for individualized treatment and targeted therapies in patients with endometrial cancer.
Phase I Trial of Daily Oral Polyphenon E in Patients With Asymptomatic Rai Stage 0 to II Chronic Lymphocytic Leukemia
Authors: Shanafelt Tait D. , Call Tim G. , Zent Clive S. , LaPlant Betsy , Bowen Deborah A. , Roos Michelle , Secreto Charla R. , Ghosh Asish K. , Kabat Brian F. , Lee Mao-Jung , Yang Chung S. , Jelinek Diane F. , Erlichman Charles , Kay Neil E.
Published: May 2009

Purpose

To define the optimal dose of Polyphenon E for chronic daily administration and tolerability in patients with chronic lymphocytic leukemia (CLL).

Patients and Methods

Previously untreated patients with asymptomatic Rai stage 0 to II CLL were eligible for participation. Polyphenon E with a standardized dose of epigallocatechin-3-gallate (EGCG) was administered using the standard phase I design with three to six patients per dose level (range, 400 to 2,000 mg by mouth twice a day). Trough plasma EGCG levels were measured 1 month after initiation of therapy. Response was classified using the National Cancer Institute (NCI) Working Group (WG) Criteria.

Results

Thirty-three eligible patients were accrued to dose levels 1 to 8. The maximum-tolerated dose was not reached. The most common adverse effects included transaminitis (33%, all grade 1), abdominal pain (30% grade 1, 0% grade 2, and 3% grade 3), and nausea (39% grade 1 and 9% grade 2). One patient experienced an NCI WG partial remission. Other signs of clinical activity were also observed, with 11 patients (33%) having a sustained ≥ 20% reduction in absolute lymphocyte count (ALC) and 11 (92%) of 12 patients with palpable adenopathy experiencing at least a 50% reduction in the sum of the products of all nodal areas during treatment. Trough plasma EGCG levels after 1 month of treatment ranged from 2.9 to 3,974 ng/mL (median, 40.4 ng/mL).

Conclusion

Daily oral EGCG in the Polyphenon E preparation was well tolerated by CLL patients in this phase I trial. Declines in ALC and/or lymphadenopathy were observed in the majority of patients. A phase II trial to evaluate efficacy using 2,000 mg twice a day began in November 2007.
The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes
Authors: Laloi-Michelin M. , Meas T. , Ambonville C. , Bellanné-Chantelot C. , Beaufils S. , Massin P. , Vialettes B. , Gin H. , Timsit J. , Bauduceau B. , Bernard L. , Bertin E. , Blickle J.-F. , Cahen-Varsaux J. , Cailleba A. , Casanova S. , Cathebras P. , Charpentier G. , Chedin P. , Crea T. , Delemer B , Dubois-Laforgue D. , Duchemin F. , Ducluzeau P. H. , Bouhanick B. , Dusselier L. , Gabreau T. , Grimaldi A. , Guerci B. , Jacquin V. , Kaloustian E. , Larger E. , Lecleire-Collet A. , Lorenzini F. , Louis J. , Mausset J. , Murat A. , Nadler-Fluteau S. , Olivier F. , Paquis-Flucklinger V. , Paris-Bockel D. , Raynaud I. , Reznik Y. , Riveline J. P. , Schneebeli S. , Sonnet E. , Sola-Gazagnes A. , Thomas J. L. , Trabulsi B. , Virally M. , Guillausseau P. J. ,   (GEDIAM, Mitochondrial Diabetes French Study Group)
Published: May 2009

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue.

Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes.

Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded.

Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender.

Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.
Proteomics in Thyroid Tumor Research
Authors: Krause Kerstin , Jeßnitzer Beate , Fuhrer Dagmar , Führer-Sakel Dagmar
Published: May 2009

Background: In recent years, “OMICS” technologies have paved novel ways for the broad-scale identification of molecular signatures and signaling pathways specific to tumorigenesis. Related to this are high hopes for the discovery of biomarkers facilitating diagnosis and prognosis of cancer as well as the option for pathway-targeted tumor treatment. Among the different OMICS methods, the potential of proteomics is just beginning to emerge, and according to the current literature, the proteome is to date the most feasible tool to reflect tumor biology.

Objective: In this review we discuss the application of proteomics to the field of thyroid tumor research.

Context: First, we provide an overview of different methods for protein expression profiling and then discuss specific requirements and challenges of thyroid proteomics. Furthermore, we summarize results of published proteomics studies on human thyroid tumors and finally explore perspectives of thyroid proteomics, which, combined with mRNA expression profiling and traditional biochemical methods, is increasingly contributing to an improved understanding of thyroid tumorigenesis and may in the future open novel avenues in thyroid cancer therapy.
An Update on Central Nervous System Stimulant Formulations in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder
Authors: Chavez Benjamin , Sopko Michael A , Ehret Megan J , Paulino Raphael E , Goldberg Kyle R , Angstadt Kristine , Bogart Gregory T
Published: May 2009

Objective

To review recent literature on the different stimulant preparations regarding efficacy and safety in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and describe advantages and disadvantages of the many available dosage formulations.

Data Sources

Literature retrieval was performed through PubMed/MEDLINE (2005–December 2008) using the terms methylphenidate, amphetamines, central nervous system stimulants, and attention-deficit/hyperactivity disorder. In addition, reference citations from publications identified were reviewed and drug manufacturers were contacted for any possible additional references.

Study Selection And Data Extraction

Double-blind clinical trials found using the search criteria listed above were included for review. Open-label studies and studies prior to 2005 were included if no double-blind trials were published for that formulation within the time period reviewed.

Data Synthesis

The literature reviewed here demonstrates the efficacy and safety of stimulant medications in children and adolescents with ADHD. However, there are 19 different formulations of stimulants, leading to confusion and errors in prescribing and dispensing of these drugs. Knowing and understanding the advantages and disadvantages of the different formulations can lead to individualized treatment. Formulations like Concerta, Focalin-XR, Adderall-XR, and Vyvanse provide the convenience of once-daily dosing. Each of these provides varying amount of stimulants at different times of the day. Vyvanse has a unique delivery system that may lower the risk of patients abusing their medication. Daytrana gives patients more control over their dosing by being able to choose when the patch is removed; it is also a feasible alternative for children who cannot swallow pills. For patients who cannot swallow tablets or capsules, the capsules of Focalin-XR, Adderall-XR, Metadate-CD, and Ritalin-LA can be opened and sprinkled on applesauce.

Conclusions

Stimulants are effective medications to treat the symptoms of ADHD. The multiple available dosage forms allow for individualization of treatment.
Health Beliefs and Over-the-Counter Product Use
Authors: Häußinger Constanze , Ruhl Uwe E , Hach Isabel
Published: May 2009

Background

Pharmacists are often consulted as medical advisors. Given this case, customers and pharmacists should interact in a trustful way (eg, in terms of responding to customer's needs or recommending a different drug). Consideration of the health beliefs of the customer could improve the interaction between pharmacists and their clients and have a positive impact on medical adherence.

Objective

To examine the health beliefs of pharmacy customers in Germany, the impact of those beliefs on over-the-counter (OTC) medication use, and associations with sociodemographic variables.

Methods

By means of literature review and methodical surveys, a standardized questionnaire was designed that contained 68 items concerning health beliefs, habits of OTC product use, decision criteria that customers used when purchasing drugs, and information about the sociodemographic background of the participants. Main outcome measures were reliability (Cronbach's α) and correlations. A random sample of 58 pharmacies in Saxony, Germany (10 questionnaires per pharmacy), invited their customers to take part in our study.

Results

One hundred twenty-three questionnaires (response rate 53.48%) were completed and returned to us. The outcome suggests that there is a strong association between health beliefs and frequency of use or the type of OTC drug (eg, illness attributions: p < 0.05; preventive lifestyle: p < 0.05). There were no significant associations between sociodemographic variables and chosen drugs.

Conclusions

Health beliefs, in terms of the general attitude toward health and illness, illness attribution, prevention, and the attitude toward treatment strategies, influence the kind of remedy (conventional vs complementary medication) that consumers seek. These results may have implications for consultations in pharmacies or for product marketing.