bluuebunny/crossref_metadata_2025 huggingface dataset:
Consensus Statement on Genetic Research in Dementia
Authors: Olde Rikkert Marcel G. M. , van der Vorm Anco , Burns Alistair , Dekkers Wim , Robert Philipp , Sartorius Norman , Selmes Jacques , Stoppe Gabriela , Vernooij-Dassen Myrra , Waldemar Gunhild
Published: May 2008

In this article, the authors describe how the European Dementia Consensus Network developed a consensus on research ethics in dementia, taking into account the questions posed by the era of genetic research and its new research methods. The consensus process started with a Delphi procedure to analyze relevant stakeholders' positions by describing their statements on the possibilities and limitations of research into genetic determinants of Alzheimer disease and to describe and analyze the moral desirability of genetic research on Alzheimer disease. The conclusions drawn from the Delphi procedure fuelled the development of the consensus statement, which is presented in this paper. The consensus statement aims to stimulate ethically acceptable research in the field of dementia and the protection of vulnerable elderly patients with dementia from application of inadequate research methods or designs.
Contact, Complicity, Conspiracy: Affective Communities and Economies of Affect in Naples
Authors: Pine Jason
Published: May 2008

This paper tracks how difficult material conditions are lived on the level of affect among ordinary underemployed families engaged in the locally named practice “the art of making do” in the contact zone where the informal and illicit economies meet. This zone is where tens of thousands of ordinary underemployed Neapolitans and the camorra, Naples' powerful and diffuse organized crime networks participate in a shared, albeit volatile, affective community. Affect is a pre-personal experience of intensity, the ability to affect or be affected. Affective community in Naples is less an identity or organization than it is a synergy, event or practice. It is experienced as a blend of fear, recognition and tolerance through the phenomena of contact, complicity and conspiracy.
Feeble Echoes of the Heart: A Postcolonial Legal Struggle in Hawai`i
Authors: Milner Neal , Goldberg-Hiller Jonathan
Published: May 2008

This article analyzes the legal discourse of native Hawaiians opposed to proposed federal recognition. We argue that this contemporary contest over the means of self-determination reveals the ways in which law and rights provide inescapable idioms for indigenous sovereignty at the same time that they form the primary obstacles that must be overcome. Strategic maneuvering through this postcolonial legal dilemma is shown to produce new ideas of law's authority, challenging dominant notions of place and time, as well as the performance of legal recognition.
Towards a Poethics of Terror
Authors: Ward Ian
Published: May 2008

The contempoprary experience of terrorism asks considerable questions of classical conceptions of law and legal theory in the field of political violence. These questions are rooted in problems of definition, and they are not reserved to the discipline of law. It has been argued that terrorism is an innately mythic construct, and that the world in which the terrorist, and counter-terrorist, operates, is one of collective enchantment. This article is premised upon this supposition. It argues that a `poethical' approach, one that embraces the particular disciplinary insights of language and literature, presents a vital supplement to present jurisprudential endeavors to comprehend terrorism. The first part of the article argues the case for a poethics of terror. The second and third then discuss the particular treatment of terrorism in the novels of Joseph Conrad, Feodor Dostoevsky and J.M. Coetzee. The final part of the article reiterates the particular strategic value of a poethical approach in our endeavor to access an ethical, as well as political and cultural, understanding of modern terrorism.
August Wilson's The Piano Lesson and the Limits of Law
Authors: Tackach James , Benoit Emilie
Published: May 2008

August Wilson's The Piano Lesson features a debate between an African American brother and sister over the ownership of a richly symbolic piano, a family heirloom that represents the Charles family's slave heritage and its endurance through Reconstruction. Ownership questions like the one presented in The Piano Lesson can usually be resolved in the courts, but Wilson's play suggests that the law might be unable to resolve property disputes so problematically entangled with the legacy of slavery. Wilson offers, instead, a non-legal resolution to the piano debate presented in his play.
Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+CD27+ B cells harbor the virus in X-linked lymphoproliferative disease patients
Authors: Chaganti Sridhar , Ma Cindy S. , Bell Andrew I. , Croom-Carter Debbie , Hislop Andrew D. , Tangye Stuart G. , Rickinson Alan B.
Published: May 2008

Epstein-Barr virus (EBV) persists in healthy virus carriers within the immunoglobulin (Ig)D−CD27+ (class-switched) memory B-cell compartment that normally arises through antigen stimulation and germinal center transit. Patients with X-linked lymphoproliferative disease (XLP) lack such class-switched memory B cells but are highly susceptible to EBV infection, often developing fatal symptoms resembling those seen in EBV-associated hemophagocytic syndrome (EBV-AHS), a disease caused by aberrant virus entry into the NK- or T-cell system. Here we show that XLP patients who survive primary EBV exposure carry relatively high virus loads in the B-cell, but not the NK- or T-cell, compartment. Interestingly, in the absence of conventional class-switched memory B cells, the circulating EBV load was concentrated within a small population of IgM+IgD+CD27+ (nonswitched) memory cells rather than within the numerically dominant naive (IgM+IgD+CD27−) or transitional (CD10+CD27−) subsets. In 2 prospectively studied patients, the circulating EBV load was stable and markers of virus polymorphism detected the same resident strain over time. These results provide the first definitive evidence that EBV can establish persistence in the B-cell system in the absence of fully functional germinal center activity and of a class-switched memory B-cell compartment.
Heme oxygenase-1 deficiency leads to disrupted response to acute stress in stem cells and progenitors
Authors: Cao Yu-An , Wagers Amy J. , Karsunky Holger , Zhao Hui , Reeves Robert , Wong Ronald J. , Stevenson David K. , Weissman Irving L. , Contag Christopher H.
Published: May 2008

An effective response to extreme hematopoietic stress requires an extreme elevation in hematopoiesis and preservation of hematopoietic stem cells (HSCs). These diametrically opposed processes are likely to be regulated by genes that mediate cellular adaptation to physiologic stress. Herein, we show that heme oxygenase-1 (HO-1), the inducible isozyme of heme degradation, is a key regulator of these processes. Mice lacking one allele of HO-1 (HO-1+/−) showed accelerated hematopoietic recovery from myelotoxic injury, and HO-1+/− HSCs repopulated lethally irradiated recipients with more rapid kinetics. However, HO-1+/− HSCs were ineffective in radioprotection and serial repopulation of myeloablated recipients. Perturbations in key stem cell regulators were observed in HO-1+/− HSCs and hematopoietic progenitors (HPCs), which may explain the disrupted response of HO-1+/− HPCs and HPCs to acute stress. Control of stem cell stress response by HO-1 presents opportunities for metabolic manipulation of stem cell–based therapies.
Effects of glucocorticoids in ventilated piglets with severe pneumonia
Authors: Sibila O. , Luna C. M. , Agustí C. , Baquero S. , Gando S. , Patrón J. R. , Morato J. G. , Absi R. , Bassi N. , Torres A.
Published: May 2008

There is clinical evidence suggesting that glucocorticoids may be useful in severe pneumonia, but the pathogenic mechanisms explaining these beneficial effects are unknown.

The aim of the present study was to determine the effects of adding glucocorticoids to antibiotic treatment in an experimental model of severe pneumonia.

In total, 15 Lagerwhite-Landrace piglets were ventilated for 96 h. After intubation, a 75 mL solution containingPseudomonas aeruginosa(106 cfu·mL−1) was bronchoscopically inoculated. The animals were randomised into three groups 12 h after inoculation: 1) untreated; 2) treated with ciprofloxacin; and 3) treated with ciprofloxacin plus methylprednisolone. Physiological and laboratory parameters were monitored throughout the study. Pro-inflammatory cytokines were measured in serum and bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed.

At the end of the study, piglets receiving the antibiotic plus glucocorticoids showed: 1) a decrease in the concentration of interleukin-6 in BAL; and 2) a decrease in the global bacterial burden both in BAL and lung tissue.

In conclusion, in this experimental model of pneumonia, the association of glucocorticoids with antibiotics attenuates local inflammatory response and decreases bacterial burden in the lung.
Treatment with inhaled steroids in patients with symptoms suggestive of asthma but with normal lung function
Authors: Rytilä P. , Ghaly L. , Varghese S. , Chung W. , Selroos O. , Haahtela T.
Published: May 2008

A total of 144 patients with lower airway symptoms suggestive of asthma, but who did not fulfil the functional criteria of asthma, were included in a randomised, double-blind, placebo-controlled 8-week “proof-of-concept” study with mometasone furoate (MF), 400 µg once daily. The primary efficacy variable was the mean change from baseline in six morning and evening weekly symptom scores: cough, sputum production, wheeze, shortness of breath, chest tightness and exercise-induced cough/wheeze. Total symptom scores were calculated after treatment for 4 and 8 weeks.

Compared with placebo, MF improved total morning symptom score at 8 weeks. Changes in total evening symptom scores did not differ between treatments. MF improved all individual symptom scores more than placebo, although the differences in changes between treatments were not always statistically significant. Morning and evening peak expiratory flow rates increased with MF compared with placebo. MF reduced eosinophils and the levels of eosinophilic cationic protein in induced sputum.

The results show that symptoms suggestive of asthma exist in patients without significant β2-agonist reversibility or diurnal variability in peak flow. Once-daily MF may benefit some of these patients and a short course with inhaled corticosteroids may be tried. Responders should be better identified in further studies.
Haem oxygenase-1 plays a central role in NNK-mediated lung carcinogenesis
Authors: Li M-Y. , Yip J. , Hsin M. K. Y. , Mok T. S. K. , Wu Y. , Underwood M. J. , Chen G. G.
Published: May 2008

The tobacco-specific nitrosamine, 4-(N-methyl-N-nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent lung cancer inducer. However, how NNK induces lung cancer is still largely unknown.

Haem oxygenase (HO)-1 was evaluated in 30 pairs of lung cancer tumour samples and matched nontumour tissues from patients with a history of cigarette smoking. Expression of HO-1, p21Cip1/Waf1/Cid1(p21), B-cell lymphoma (Bcl)-2 family members, mitogen-activated protein kinase and nuclear factor (NF)-κB was also studied in lung cancer cells treated with NNK.

The levels of HO-1 and p21 were significantly increased in lung tumour tissues. There was a positive relationship between these two proteins in the tumour. NNK stimulated lung cell proliferation and elevated the levels of HO-1, p21, inhibitor of apoptosis protein (c-IAP)2 and Bcl-2, but downregulated Bad. These effects of NNK were blocked by zinc protoporphyrin-XII, an HO-1 inhibitor. The NNK-mediated expression of HO-1 was governed by NF-κB and extracellular signal-regulated kinase 1/2, since blocking either of these prevented the stimulatory effect of NNK on HO-1, as well as molecules downstream of HO-1, such as p21, c-IAP2, Bcl-2 and Bad.

In conclusion, haem oxygenase-1 plays a central role in NNK-mediated cell proliferation by promoting the expression of p21Cip1/Waf1/Cid1, inhibitor of apoptosis protein 2 and B-cell lymphoma-2 but inhibiting the activity of Bad. Nuclear factor-κB and extracellular signal-regulated kinase 1/2 function upstream of haem oxygenase-1. Therefore, haem oxygenase-1 is likely to be a potential target in the treatment of smoking-related lung cancer.
Can CAP guideline adherence improve patient outcome in internal medicine departments?
Authors: Blasi F. , Iori I. , Bulfoni A. , Corrao S. , Costantino S. , Legnani D.
Published: May 2008

The impact of compliance with Italian guidelines on the outcome of hospitalised community-acquired pneumonia (CAP) in internal medicine departments was evaluated.

All Fine class IV or V CAP patients were included in this multicentre, interventional, before-and-after study, composed of three phases: 1) a retrospective phase (RP; 1,443 patients); 2) a guideline implementation phase; and 3) a prospective phase (PP; 1,404 patients).

Antibiotic prescription according to the guidelines increased significantly in the PP. The risk of failure at the end of the firstline therapy was significantly lower in the PPversusthe RP (odds ratio (OR) 0.83, 95% confidence interval (CI) 0.69–1.00), particularly in Fine class V patients (OR 0.71, 95% CI 0.51–0.98). Analysis of outcome in the overall population (2,847 patients) showed a statistically significant advantage for compliantversusnoncompliant therapies in terms of failure rate (OR 0.74, 95% CI 0.60–0.90) and an advantage in terms of mortality (OR 0.77, 95% CI 0.58–1.04). Antipneumococcal cephalosporin monotherapy was associated with a low success rate (68.6%) and the highest mortality (16.2%); levofloxacin alone and the combination of cephalosporin and macrolide resulted in higher success rates (79.1 and 76.7%, respectively) and significantly lower mortalities (9.1 and 5.7%, respectively).

Overall, a low compliance with guidelines in the prospective phase (44%) was obtained, indicating the need for future more aggressive and proactive approaches.
Efficacy of a cell phone-based exercise programme for COPD
Authors: Liu W-T. , Wang C-H. , Lin H-C. , Lin S-M. , Lee K-Y. , Lo Y-L. , Hung S-H. , Chang Y-M. , Chung K.F. , Kuo H-P.
Published: May 2008

The application of a supervised endurance exercise training programme in a home setting offering convenience and prolonged effects is a challenge.

In total, 48 patients were initially assessed by the incremental shuttle walk test (ISWT), spirometry and the Short Form-12 (SF-12) quality-of-life questionnaire, and then every 4 weeks for 3 months thereafter and again after 1 yr. During the first 3 months, 24 patients in the cell phone group were asked to perform daily endurance walking at 80% of their maximal capacity by following the tempo of music from a program installed on a cell phone. The level of endurance walking at home was readjusted monthly according to the result of ISWT. In the control group, 24 patients received the same protocol and were verbally asked to take daily walking exercise at home.

Patients in the cell phone group significantly improved their ISWT distance and duration of endurance walking after 8 weeks. The improvements in ISWT distance, inspiratory capacity and SF-12 scoring at 12 weeks persisted until the end of the study, with less acute exacerbations and hospitalisations.

In the present pilot study, the cell phone-based system provides an efficient, home endurance exercise training programme with good compliance and clinical outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease.
Outdoor swimming pools and the risks of asthma and allergies during adolescence
Authors: Bernard A. , Nickmilder M. , Voisin C.
Published: May 2008

Exposure to indoor chlorinated swimming pools can be detrimental to the airways of swimmers and increase asthma risks but it is unknown whether these effects concern outdoor pools.

The present study examined 847 secondary school adolescents who had attended residential or nonresidential outdoor chlorinated pools at a variable rate. The main outcomes were: ever asthma (physician-diagnosed at any time); current asthma (ever asthma under medication and/or with exercise-induced bronchoconstriction); elevated exhaled nitric oxide; and aeroallergen-specific immunoglobulin (Ig)E in serum.

The prevalence of ever and current asthma significantly increased with the lifetime number of hours spent in outdoor pools by up to four and eight times, respectively, among adolescents with the highest attendance (>500 h) and a low exposure to indoor pools (<250 h). Odds for asthma were significantly increased among adolescents with total serum IgE >25 kIU·L−1, on average by 1–2 units for each 100-h increase in pool attendance. Use of residential outdoor pools was also associated with higher risks of elevated exhaled nitric oxide and sensitisation to cat or house dust mite allergens.

Outdoor chlorinated swimming pool attendance is associated with higher risks of asthma, airways inflammation and some respiratory allergies.
Exhaled nitric oxide predicts lung function decline in difficult-to-treat asthma
Authors: van Veen I. H. , ten Brinke A. , Sterk P. J. , Sont J. K. , Gauw S. A. , Rabe K. F. , Bel E. H.
Published: May 2008

A subset of patients with asthma is known to have progressive loss of lung function despite treatment with corticosteroids. The aim of the present study was to identify risk factors of decline in forced expiratory volume in one second (FEV1) in patients with difficult-to-treat asthma.

In total, 136 nonsmoking patients with difficult-to-treat asthma were recruited between 1998 and 1999. Follow-up assessment was performed 5–6 yrs later in 98 patients. The predictive effect of clinical characteristics and inflammatory markers were analysed at baseline (asthma onset and duration, atopy, airway hyperresponsiveness, blood and sputum eosinophils, and the fraction of nitric oxide in exhaled air (FeNO)) on subsequent decline in post-bronchodilator FEV1.

Patients with highFeNO(≥20 ppb) had an excess decline of 40.3 (95% confidence interval (CI) 7.3–73.2) mL·yr−1compared to patients with lowFeNO.FeNO≥20 ppb was associated with a relative risk of 1.9 (95% CI, 1.1–2.6) of having an accelerated (≥25 mL·yr−1) decline in FEV1. In patients with baseline FEV1≥80% of predicted, this relationship was even stronger: 90versus29% had accelerated decline in FEV1(FeNO≥20 ppbversusFeNO<20 ppb respectively; relative risk 3.1 (95% CI, 1.7–3.4).

Exhaled nitric oxide is a predictor of accelerated decline in lung function in patients with difficult-to-treat asthma, particularly if forced expiratory volume in one second is still normal.
Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma
Authors: Wu S-G. , Gow C-H. , Yu C-J. , Chang Y-L. , Yang C-H. , Hsu Y-C. , Shih J-Y. , Lee Y-C. , Yang P-C.
Published: May 2008

Malignant pleural effusions (MPEs) are often observed in lung cancer, especially adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in lung adenocarcinoma. The purpose of the present study was to investigate theEGFRmutation rate in MPEs of lung adenocarcinoma.

Between June 2005 and December 2006, 136 MPEs from lung adenocarcinoma were collected forEGFRmutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of lung adenocarcinoma from patients without MPEs were assessed forEGFRmutation.

TheEGFRmutation rate was significantly higher in the patients with MPEs than in the patients without (68.4%versus50.5%). TheEGFRmutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0–1, andEGFRmutation were significantly associated with a longer overall survival for lung adenocarcinoma patients with MPEs.

The patients with malignant pleural effusions related to lung adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for lung adenocarcinoma with malignant pleural effusions in east Asia.
Nutritional deficit as a negative prognostic factor in patients with miliary tuberculosis
Authors: Kim D. K. , Kim H. J. , Kwon S-Y. , Yoon H-I. , Lee C-T. , Kim Y. W. , Chung H. S. , Han S. K. , Shim Y-S. , Lee J-H.
Published: May 2008

The effects of malnutrition on outcomes in miliary tuberculosis (MTB) are not well described. The aim of the present study was to find predictors for the development of acute respiratory failure (ARF) and survival in MTB patients, focusing on parameters reflecting nutritional condition.

Out of the patients from three hospitals who had microbiologically or histopathologically confirmed tuberculosis, 56 patients presenting with typical disseminated pulmonary nodules on radiographs were retrospectively enrolled. A four-point nutritional risk score (NRS) was defined according to the presence of four nutritional factors: low body mass index (BMI; <18.5 kg·m−2), hypoalbuminaemia (<30.0 g·L−1), hypocholesterolaemia (<2.33 mmol·L−1) and severe lymphocytopenia (<7×105 cells·L−1).

The male to female ratio was 1:3. ARF developed in 25% of patients (14 out of 56), with a 50% fatality rate. A high NRS (≥3 points) was an independent risk factor for the development of ARF and fatality. In 90-day survival analysis, ARF, severe lymphocytopenia, hypocholesterolaemia, low BMI and higher NRS were risk factors for poor outcome. In multivariate analysis, only high NRS was an independent risk factor for 90-day survival rate in patients with MTB.

A high nutritional risk score was a good predictor of poor outcome in miliary tuberculosis patients. Additional approaches to recover the nutritional deficits may become a focus in future management of miliary tuberculosis.
Sequencing and genotypic analysis of the triosephosphate isomerase (TPI1) locus in a large sample of long-lived Germans
Authors: Ralser Markus , Nebel Almut , Kleindorp Rabea , Krobitsch Sylvia , Lehrach Hans , Schreiber Stefan , Reinhardt Richard , Timmermann Bernd
Published: May 2008

Background

Triosephosphate isomerase (TPI) is a central and conserved glycolytic enzyme. In humans, TPI is encoded by a single gene on 12p13, and associated with a rare genetic disorder, TPI deficiency. Reduced TPI activity can increase specific oxidant resistances of model organisms and TPI null-alleles have been hypothesized to promote a heterozygote advantage in man. However, comprehensive genetic information about the TPI1 locus is still lacking.

Results

Here, we sequenced the TPI1 locus in a sample of 357 German long-lived individuals (LLI) aged 95 to 110 years. We identified 17 different polymorphisms, of which 15 were rare and previously unknown. The two remaining SNPs occurred at much higher frequency and were tested for association with the longevity phenotype in larger samples of LLI (n = 1422) and younger controls (n = 967). Neither of the two markers showed a statistically significant difference in allele or genotype frequency between LLI and control subjects.

Conclusion

This study marks the TPI1 locus as extraordinarily conserved, even when analyzing intronic and non-coding regions of the gene. None of the identified sequence variations affected the amino acid composition of the TPI protein and hence, are unlikely to impact the catalytic activity of the enzyme. Thus, TPI variants occur less frequent than expected and inactive alleles are not enriched in German centenarians.
Exploiting orthologue diversity for systematic detection of gain-of-function phenotypes
Authors: Martelli Maria Luisa , Isella Claudio , Mira Alessia , Fu Limin , Cantarella Daniela , Medico Enzo
Published: May 2008

Background

Systematic search for genes whose gain-of-function by exogenous expression confers an advantage in cell-based selective screenings is a powerful method for unbiased functional exploration of the genome, and has the potential to disclose new targets for cancer therapy. A major limit of this approach resides in the labor-intensive cloning of resistant cells, identification of the integrated genes and validation of their ability to confer a selective advantage. Moreover, the selection has to be drastic and genes conferring a limited advantage are typically missed.

Results

We developed a new functional screening strategy based on transduction of mammalian cells of a given species with an expression library from another species, followed by one-shot quantitative tracing with DNA microarrays of all library-derived transcripts before and after selection. In this way, exogenous transcripts enriched after selection, and therefore likely to confer resistance, are readily detected. We transduced a retroviral cDNA expression library from mouse testis into human and canine cells, and optimized the use of commercial murine gene expression arrays for species-specific detection of library-derived transcripts. We then conducted a functional screening by growing library-transduced canine MDCK cells in suspension, to enrich for cDNAs conferring anchorage independence. Notably, these cells show partial resistance to loss of anchorage, and the selection can be of limited stringency, compromising approaches based on clonal selection or anyway requiring high stringency. Microarray analysis revealed reproducible enrichment after three weeks of growth on polyhema for seven genes, among which the Hras proto-oncogene and Sox5. When individually transduced into MDCK cells, Sox5 specifically promoted anchorage-independent growth, thereby confirming the validity and specificity of the approach.

Conclusion

The procedure described here brings substantial advantages to the field of expression cloning, being faster, more systematic and more sensitive. Indeed, this strategy allowed identification and validation of genes promoting anchorage-independent growth of epithelial cells under selection conditions not amenable to conventional expression cloning.
Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries
Authors: Camargo Enilton A , Delbin Maria Andréia , Ferreira Tatiane , Landucci Elen CT , Antunes Edson , Zanesco Angelina
Published: May 2008

Background

Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO) production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis.

Male Wistar rats were divided into three groups: saline (SAL); tauracholate (TAU) and phospholipase A2 (PLA2). Pancreatitis was induced by administration of TAU or PLA2 from Naja mocambique mocambique into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PHE) in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC50) and maximal responses (EMAX) were determined. Blood samples were collected for biochemical analysis.

Results

In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold) or PLA2 (about 6.9-fold) compared to saline group without changes in the maximal responses. Neither pEC50 nor EMAX values for Ach were altered in pulmonary rings in any group. Similarly, the pEC50 and the EMAX values for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively). No changes were seen in the EMAX for PHE. The nitrite/nitrate (NOx
-) levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA2 protocol, respectively.

Conclusion

Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NOx
- levels as consequence of intense inflammatory responses. Furthermore, the subsensitivity of contractile response to PHE in both mesenteric and pulmonary rings might be due to the complications of this pathological condition in the early stage of pancreatitis.
Characterization of three new serous epithelial ovarian cancer cell lines
Authors: Ouellet Véronique , Zietarska Magdalena , Portelance Lise , Lafontaine Julie , Madore Jason , Puiffe Marie-Line , Arcand Suzanna L , Shen Zhen , Hébert Josée , Tonin Patricia N , Provencher Diane M , Mes-Masson Anne-Marie
Published: May 2008

Background

Cell lines constitute a powerful model to study cancer, and here we describe three new epithelial ovarian cancer (EOC) cell lines derived from poorly differentiated serous solid tumors (TOV-1946, and TOV-2223G), as well as the matched ascites for one case (OV-1946).

Methods

In addition to growth parameters, the cell lines were characterized for anchorage independent growth, migration and invasion potential, ability to form spheroids and xenografts in SCID mice.

Results

While all cell lines were capable of anchorage independent growth, only the TOV-1946 and OV-1946 cell lines were able to form spheroid and produce tumors. Profiling of keratins, p53 and Her2 protein expression was assessed by immunohistochemistry and western blot analyses. Somatic TP53 mutations were found in all cell lines, with TOV-1946 and OV-1946 harboring the same mutation, and none harbored the commonly observed somatic mutations in BRAF, KRAS or germline BRCA1/2 mutations found to recur in the French Canadian population. Conventional cytogenetics and spectral karyotype (SKY) analyses revealed complex karyotypes often observed in ovarian disease.

Conclusion

This is the first report of the establishment of matched EOC cell lines derived from both solid tumor and ascites of the same patient.
JNK pathway is involved in the inhibition of inflammatory target gene expression and NF-kappaB activation by melittin
Authors: Park Hye Ji , Lee Hwa Jeong , Choi Myung Sook , Son Dong Ju , Song Ho Sueb , Song Min Jong , Lee Jeong Min , Han Sang Bae , Kim Youngsoo , Hong Jin Tae
Published: May 2008

Background

Bee venom therapy has been used to treat inflammatory diseases including rheumatoid arthritis in humans and in experimental animals. We previously found that bee venom and melittin (a major component of bee venom) have anti-inflammatory effect by reacting with the sulfhydryl group of p50 of nuclear factor-kappa B (NF-κB) and IκB kinases (IKKs). Since mitogen activated protein (MAP) kinase family is implicated in the NF-κB activation and inflammatory reaction, we further investigated whether activation of MAP kinase may be also involved in the anti-inflammatory effect of melittin and bee venom.

Methods

The anti-inflammatory effects of melittin and bee venom were investigated in cultured Raw 264.7 cells, THP-1 human monocytic cells and Synoviocytes. The activation of NF-κB was investigated by electrophoretic mobility shift assay. Nitric oxide (NO) and prostaglandin E2(PGE2) were determined either by Enzyme Linked Immuno Sorbent Assay or by biochemical assay. Expression of IκB, p50, p65, inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2) as well as phosphorylation of MAP kinase family was determined by Western blot.

Results

Melittin (0.5–5 μg/ml) and bee venom (5 and 10 μg/ml) inhibited lipopolysaccharide (LPS, 1 μg/ml) and sodium nitroprusside (SNP, 200 μM)-induced activation of c-Jun NH2-terminal kinase (JNK) in RAW 264.7 cells in a dose dependent manner. However, JNK inhibitor, anthra [1,9-cd]pyrazole-6 (2H)-one (SP600215, 10–50 μM) dose dependently suppressed the inhibitory effects of melittin and bee venom on NF-κB dependent luciferase and DNA binding activity via suppression of the inhibitory effect of melittin and bee venom on the LPS and SNP-induced translocation of p65 and p50 into nucleus as well as cytosolic release of IκB. Moreover, JNK inhibitor suppressed the inhibitory effects of melittin and bee venom on iNOS and COX-2 expression, and on NO and PGE2generation.

Conclusion

These data show that melittin and bee venom prevent LPS and SNP-induced NO and PGE2production via JNK pathway dependent inactivation of NF-κB, and suggest that inactivation of JNK pathways may also contribute to the anti-inflammatory and anti-arthritis effects of melittin and bee venom.
Expression of novel extracellular sulfatases Sulf-1 and Sulf-2 in normal and osteoarthritic articular cartilage
Authors: Otsuki Shuhei , Taniguchi Noboru , Grogan Shawn P , D'Lima Darryl , Kinoshita Mitsuo , Lotz Martin
Published: May 2008

Introduction

Changes in sulfation of cartilage glycosaminoglycans as mediated by sulfatases can regulate growth factor signaling. The aim of this study was to analyze expression patterns of recently identified extracellular sulfatases Sulf-1 and Sulf-2 in articular cartilage and chondrocytes.

Methods

Sulf-1 and Sulf-2 expressions in human articular cartilage from normal donors and patients with osteoarthritis (OA) and in normal and aged mouse joints were analyzed by real-time polymerase chain reaction, immunohistochemistry, and Western blotting.

Results

In normal articular cartilage, Sulf-1 and Sulf-2 mRNAs and proteins were expressed predominantly in the superficial zone. OA cartilage showed significantly higher Sulf-1 and Sulf-2 mRNA expression as compared with normal human articular cartilage. Sulf protein expression in OA cartilage was prominent in the cell clusters. Western blotting revealed a profound increase in Sulf protein levels in human OA cartilage. In normal mouse joints, Sulf expression was similar to human cartilage, and with increasing age, there was a marked upregulation of Sulf.

Conclusion

The results show low levels of Sulf expression, restricted to the superficial zone in normal articular cartilage. Sulf mRNA and protein levels are increased in aging and OA cartilage. This increased Sulf expression may change the sulfation patterns of heparan sulfate proteoglycans and growth factor activities and thus contribute to abnormal chondrocyte activation and cartilage degradation in OA.
Leg-length inequality is not associated with greater trochanteric pain syndrome
Authors: Segal Neil A , Harvey William , Felson David T , Yang Mei , Torner James C , Curtis Jeffrey R , Nevitt Michael C ,   the Multicenter Osteoarthritis Study Group
Published: May 2008

Introduction

Greater trochanteric pain syndrome (GTPS) is a common condition, the pathogenesis of which is incompletely understood. Although leg-length inequality has been suggested as a potential risk factor for GTPS, this widely held assumption has not been tested.

Methods

A cross-sectional analysis of greater trochanteric tenderness to palpation was performed in subjects with complaints of hip pain and no signs of hip osteoarthritis or generalized myofascial tenderness. Subjects were recruited from one clinical center of the Multicenter Osteoarthritis Study, a multicenter population-based study of community-dwelling adults aged 50 to 79 years. Diagnosis of GTPS was based on a standardized physical examination performed by trained examiners, and technicians measured leg length on full-limb anteroposterior radiographs.

Results

A total of 1,482 subjects were eligible for analysis of GTPS and leg length. Subjects' mean ± standard deviation age was 62.4 ± 8.2 years, and 59.8% were female. A total of 372 lower limbs from 271 subjects met the definition for having GTPS. Leg-length inequality (difference ≥ 1 cm) was present in 37 subjects with GTPS and in 163 subjects without GTPS (P = 0.86). Using a variety of definitions of leg-length inequality, including categorical and continuous measures, there was no association of this parameter with the occurrence of GTPS (for example, for ≥ 1 cm leg-length inequality, odds ratio = 1.17 (95% confidence interval = 0.79 to 1.73)). In adjusted analyses, female sex was significantly associated with the presence of GTPS, with an adjusted odds ratio of 3.04 (95% confidence interval = 2.07 to 4.47).

Conclusion

The present study found no evidence to support an association between leg-length inequality and greater trochanteric pain syndrome.
Single-well acoustic imaging in anisotropic formations
Authors: Tang X. M. , Glassman H. , Patterson D.
Published: May 2008

The effect of formation anisotropy on single-well acoustic imaging was analyzed to provide a simple and effective correction method for the imaging application. We used analytical and synthetic modeling to analyze acoustic reflection moveout in a transversely isotropic (TI) formation for borehole configuration. Far-borehole reflections from a bed generally have small reflection angles to the bed. Thus the reflection moveout away from the borehole is controlled largely by the velocity along the TI-symmetry axis. Consequently, reflection imaging using measured velocity along the borehole can cause errors in the imaged reflector position. By correcting the anisotropy effect in the velocity, reflectors can be imaged correctly. A simple correction is to use the velocity along the TI-symmetry axis, which effectively maps the bed reflector to its correct position. Application of the correction method to synthetic and field-data examples demonstrate the anisotropy effect on reflector imaging and the effectiveness of the method.
mls-2andvab-3control glia development,hlh-17/Olig expression and glia-dependent neurite extension inC. elegans
Authors: Yoshimura Satoshi , Murray John I. , Lu Yun , Waterston Robert H. , Shaham Shai
Published: May 2008

Glia are essential components of nervous systems. However, genetic programs promoting glia development and regulating glia-neuron interactions have not been extensively explored. Here we describe transcriptional programs required for development and function of the C. elegans cephalic sheath(CEPsh) glia. We demonstrate ventral- and dorsal-restricted roles for the mls-2/Nkx/Hmx and vab-3/Pax6/Pax7 genes,respectively, in CEPsh glia differentiation and expression of the genes hlh-17/Olig and ptr-10/Patched-related. Using mls-2and vab-3 mutants, as well as CEPsh glia-ablated animals, we show that CEPsh glia are important for sensory dendrite extension, axon guidance/branching within the nerve ring, and nerve ring assembly. We demonstrate that UNC-6/Netrin, expressed in ventral CEPsh glia, mediates glia-dependent axon guidance. Our results suggest possible similarities between CEPsh glia development and oligodendrocyte development in vertebrates,and demonstrate that C. elegans provides a unique environment for studying glial functions in vivo.
Experts' discussions
Authors: Smith Lucy Clements
Published: May 2008

Reports reaching the Clinical Disputes Forum (see http://www.clinicaldisputesforum.org.uk ) have suggested that the practice of experts' discussions (‘experts’ meetings') in the context of Clinical Disputes has recently encountered problems. A meeting was convened on 21 November 2007 at the Law Society, at which some of these problems were discussed. This article summarizes that debate, focusing on the ordering of discussions, agenda, timetables and the presence of lawyers – and some possible solutions are considered.
Acute compartment syndrome: reducing the risk
Authors: Pearse Michael F , Nanchahal Jagdeep
Published: May 2008

Acute limb compartment syndrome is a surgical emergency characterized by raised pressure within an unyielding tissue compartment. Although there is commonly a history of trauma there are a number of causes of compartment syndrome, which includes iatrogenic insults. The key clinical feature of a compartment syndrome in the conscious patient is severe pain out of proportion to the injury and aggravated by passive muscle stretch. Intracompartmental pressure measurements remain the only objective method of diagnosing an acute compartment syndrome. Although it is subject to false positives, interpreting the pressures in relation to the systemic blood pressure helps confirm the diagnosis when the clinical findings are equivocal and provides essential information in unconscious or uncooperative patients. Successful treatment of an acute compartment syndrome involves prompt, early diagnosis followed by an adequate surgical decompression of all four compartments of the leg by fasciotomies. Delay in diagnosis is almost invariably associated with a poor outcome and loss of limb function. As acute compartment syndromes typically occur in young patients with an average work–life expectancy of up to 30 years, a poor outcome results in severe loss of productivity.
The value proposition in the widespread use of telehealth
Authors: Cusack Caitlin M , Pan Eric , Hook Julie M , Vincent Adam , Kaelber David C , Middleton Blackford
Published: May 2008

Summary

Telehealth has great potential to improve access to care but its adoption in routine health care has been slow. The lack of clarity about the value of telehealth implementations has been one reason cited for this slow adoption. The Center for Information Technology Leadership has examined the value of telehealth encounters in which there is a provider both with the patient and at a distance from the patient. We considered three models of telehealth: store-and-forward, real-time video and hybrid systems. Evidence from the literature was extrapolated using a simulation, which found that the hybrid model was the most cost-effective of the three. The simulation predicted savings of $4.3 billion per year if hybrid telehealth systems were to be implemented in emergency rooms, prisons, nursing home facilities and physician offices across the US. We also conducted a sensitivity analysis to determine which factors most affected costs and savings. For all three telehealth models, the highest sensitivities were to the cost of a face-to-face visit, the cost of a telehealth visit and the success rate of a telehealth visit, i.e. the proportion of telehealth visits that avoided the need for a face-to-face visit. Payers, providers and policy-makers should work together to remove the barriers to the adoption of telehealth in order to make it widely available to all.
Utilization of telemedicine by heart disease patients following hospitalization
Authors: Morguet Andreas J , Kühnelt Paul , Kallel Antje , Rauch Ursula , Schultheiss Heinz-Peter
Published: May 2008

Summary

NYHA class III and IV chronic heart failure has been established as a potential indication for telemedical care and monitoring already. We conducted a prospective study to assess the utilization of telemedical services by cardiac patients in order to identify further indications. A total of 540 patients (mean age 59 years) with various heart diseases participated for at least 30 days in a home-based telemedicine service programme. The two primary outcome measures were the rates of symptom-driven telephone calls (A) and ECG transmissions (B) per patient-year. The total follow-up was 68,649 days, with a median of 93 days. Symptomatic patients placed 713 calls and transmitted 221 ECGs. Poisson regression analysis with subset selection yielded four significant ( P < 0.05) independent positive predictors of the use of the telemedicine service: (1) recent repeat (at least one previous) percutaneous coronary intervention (A, P = 0.010; B, P = 0.001); (2) recent cardioversion for atrial fibrillation or flutter (A, P < 0.0001; B, P < 0.0001); (3) ejection fraction (A, P = 0.012; B, P > 0.05); and (4) reciprocal of age (A, P < 0.0001; B, P > 0.05). These data suggest that telemedicine may benefit patients following repeat percutaneous coronary intervention or cardioversion for atrial fibrillation. Since patients availed themselves of telemedicine service less with deteriorating ejection fraction and increasing age, individuals with chronic heart failure will need dedicated programmes, especially when they are older.
Home telehealth for children with special health-care needs
Authors: Cady Rhonda , Kelly Anne , Finkelstein Stanley
Published: May 2008

Summary

The U Special Kids (USK) programme at the University of Minnesota provides intensive care coordination and case management services to children with complex special health-care needs. We conducted a one-year pilot study to evaluate the feasibility of videoconferencing between the USK office and family homes. To ensure easy installation, families were provided with prepackaged equipment and software. However, the families had different Internet providers, different modems and/or routers and different firewall software, which required case-by-case resolution during home visits by the project coordinator. Five families participated in 3–5 videoconferencing sessions with a USK nurse. All connections with urban families had clear audio and video, whereas connections with rural families had clear audio, but unclear video. All of the scheduled virtual visits were rated by nurses as providing information that was similar to a telephone call. However, the unscheduled virtual visits were rated by the nurses as providing more information than a telephone call, suggesting that home-based videoconferencing may be useful in the management of children with complex special health-care needs.
A feasibility study of home telemedicine for patients with cystic fibrosis awaiting transplantation
Authors: Wilkinson Olive M , Duncan-Skingle Frances , Pryor Jennifer A , Hodson Margaret E
Published: May 2008

Summary

Sixteen patients with cystic fibrosis were randomized to either telemedicine or standard care alone. All patients were terminally ill. Patients in the telemedicine group had an ISDN line installed in their home and were given a videoconferencing unit connected to their home television set. Eleven subjects completed the baseline assessment and seven patients completed the study (4 on telemedicine and 3 in the control arm). Telemedicine patients had weekly videoconferences from home for a clinical assessment, psychological support and the opportunity for discussion with any member of the multidisciplinary team. A total of 71 home videoconferences were conducted during the study. Anxiety levels were measured before and after the conferences. After six months there were no significant differences in quality of life, anxiety levels, depression levels, admissions to hospital or clinic attendances, general practitioner calls or intravenous antibiotic use between the two groups. However, there was a significant improvement in perception of body image for those in the telemedicine group and the patients liked and valued the service. The use of telemedicine can enhance the support that a specialist unit can provide for the patient and their family, and may reduce outpatient clinic attendances.
Elderly adults improve verbal fluency by videophone conversations: a pilot study
Authors: Mochizuki-Kawai Hiroko , Tanaka Mayumi , Suzuki Takaji , Yamakawa Yuriko , Mochizuki Satoshi , Arai Masanobu , Kawamura Mitsuru
Published: May 2008

Summary

We conducted videophone conversations with elderly adults living in a nursing home to discover whether their verbal ability was improved by repeated remote conversations. The control group comprised five elderly adults. The experimental group comprised six elderly adults, including three patients with dementia. They took part in three videophone conversations and their verbal ability was measured before and after the conversations. During the sessions, the participants and volunteers talked about themselves and participated in a quiz. In the experimental group, the mean number of words generated increased from 4.8 to 6.5 after the session ( P < 0.05); this increase was not observed in the control group. The experimental group also showed an improvement in words generated after indirect conversations. Videophone conversations appear to have some positive effects on verbal ability and may be beneficial in the cognitive rehabilitation of elderly adults.