bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Medical Therapy Is Superior to Transplantation for the Treatment of Class I, II, and III Heart Failure
Authors: Freudenberger R.S. , Kim J. , Tawfik I. , Sonnenberg F.A.
Published: July 2006

Background—

The survival benefit of heart transplantation (HT) compared with optimal medical therapy (OMT) has never been tested.

Methods and Results—

We created a decision analytic model that simulates a randomized clinical trial of OMT versus HT for each New York Heart Association (NYHA) class. The simulation calculates average life expectancy. The following assumptions were made for OMT annual mortality: class I no excess mortality from HF; class II and III based on MERIT-HF are 5.3% and 8.1%. Class IV is 12.8%, based on COPERNICUS. HT mortality rates were based on survival curves for HT 1982 to 2001. For classes I, II, and III, OMT demonstrated a life expectancy gain of 113 months (232±2.2 versus119±2.1), 38 months (152±2.1 versus 114±2.1), and 6 months (117±1.8 versus 111±2.2), respectively, over HT. Class IV favored HT with a life expectancy gain of 26 months (107±2.1 versus 81±1.4) over OMT. Sensitivity analysis revealed if improvement in OMT decreased mortality by 38% for class IV patients, OMT and HT would have equivalent life expectancies. If improvement in HT resulted in a 7% increase in post-HT survival, OMT and HT would be equivalent for class III patients. If improvement in HT resulted in a 30% increase in post-HT survival, OMT and HT would be equivalent for class II patients.

Conclusions—

Our model predicts that currently, OMT is superior to HT for classes I, II, and III, but HT is superior for class IV. However, future advances in OMT or HT may change the relative benefits of these treatment modalities.
Homograft Valved Right Ventricle to Pulmonary Artery Conduit as a Modification of the Norwood Procedure
Authors: Reinhartz Olaf , Reddy V. Mohan , Petrossian Edwin , MacDonald Malcolm , Lamberti John J. , Roth Stephen J. , Wright Gail E. , Perry Stanton B. , Suleman Sam , Hanley Frank L.
Published: July 2006

Background—

The use of a right ventricle to pulmonary artery (RV-PA) conduit in the Norwood procedure has been proposed to increase postoperative hemodynamic stability. A valve within the conduit should further decrease RV volume load. We report our clinical experience with this modification.

Methods and Results—

From February 2002 through August 2005, we performed 88 consecutive Norwood procedures using RV-PA conduits. We used composite valved conduits made from cryopreserved homograft and polytetrafluoroethylene (PTFE) in 66 cases (54 pulmonary, 12 aortic homografts), other valved conduits in 14, and unvalved PTFE in 8 cases. Hospital survival was 88.6% overall and increased to 93.1% after the initial year. Early interventions were required in 18 patients (16 for cyanosis). Prestage II cardiac catheterization was performed at a mean age of 126 days. Mean Qp/Qs was 1, with mean aortic saturation 71%, mean O
2
extraction 24%, and mean right ventricular end-diastolic pressure 9 mm Hg. Patient weight, use of an aortic homograft valve in the conduit, stage I palliation within the first year of our experience, and low O
2
extraction and high transpulmonary gradient prestage II were risk factors for overall death. Early interventions were more frequent in aortic valve conduits compared with all other conduits.

Conclusions—

The valved RV-PA conduit was associated with low early mortality after the Norwood procedure. The majority of these patients had normal cardiac output and well-maintained RV function. There may be a higher risk for early conduit interventions and death when aortic valve homografts are used in the RV-PA conduit.
Flexible Versus Nonflexible Mitral Valve Rings for Congestive Heart Failure
Authors: Spoor Martinus T. , Geltz Amy , Bolling Steven F.
Published: July 2006

Background—

Surgical intervention is playing an increasingly important therapeutic role in congestive heart failure (CHF) patients with ischemia and dilated cardiomyopathy. Their mitral regurgitation (MR) is a result of left ventricular (LV) geometrical distortion. The optimal type of ring for CHF patients with geometric ventricular-based MR is unknown. This study reviewed the results of flexible versus nonflexible complete mitral valve rings in CHF patients with geometric mitral regurgitation.

Methods and Results—

Using a prospectively maintained database, patients undergoing mitral valve reconstruction (MVR) with either a flexible or nonflexible complete ring were identified on the basis of preoperative ejection fraction (EF) ≤30% and no primary mitral pathology. These 2 groups of CHF patients with severe geometric MR were then compared in terms of recurrent MR requiring reoperation. Between 1992 and 2004, 289 patients with EF ≤30%, received an undersized complete mitral annuloplasty ring as their MVR procedure. Of these, 170 patients had a flexible complete ring. In follow-up, 16 “flexible” patients (9.4%) required a repeat procedure for significant recurrent geometric MR and CHF (10 replacements, 3 re-repairs, 3 transplants). The average time to reoperation was 2.4 years. In contrast, 119 patients with an EF ≤30% received a MVR using an undersized nonflexible complete ring. Only 3 “non-flexible” patients required a repeat operation, MVR (1), and 2 patients required a transplant. The time to reoperation was 4.0 years. A significant difference in reoperation rates, for recurrent MR, between the 2 groups (
P
=0.012). There were no differences between groups, in terms of age, ring size used, preoperative EF, LV size, MR grade, or New York Heart Association class.

Conclusions—

Patients with CHF having a flexible ring have a higher likelihood of developing recurrent MR requiring reoperation. The use of a nonflexible ring appears to significantly reduce the need for repeat surgical procedures. Further refinement and development of nonflexible ring systems, aimed at LV restoration, deserve ongoing investigation.
Outcomes of Medical Management of Acute Type B Aortic Dissection
Authors: Estrera Anthony L. , Miller Charles C. , Safi Hazim J. , Goodrick Jennifer S. , Keyhani Arash , Porat Eyal E. , Achouh Paul E. , Meada Riad , Azizzadeh Ali , Dhareshwar Jayesh , Allaham Adnan
Published: July 2006

Background—

Currently, the optimal treatment of acute type B aortic dissection remains controversial. The purpose of this study was to report early clinical outcomes of medical management for acute type B aortic dissection.

Methods and Results—

Between January 2001 and March 2005, 129 consecutive patients with the confirmed diagnosis of acute type B aortic dissection were studied. Mean age was 61 years (range, 29 to 94), with 33.3% (43/129) female. Acute type B aortic dissection protocol was instituted with the intent to manage all patients medically. Indications for surgical intervention included rupture, aortic expansion, malperfusion, and intractable pain. All patients were followed-up after discharge. Hospital mortality was 10.1% (13/129), 19% (4/21) when vascular intervention was required, and 8.3% (9/108) when medical management was maintained. Early intervention was required in 21 cases (16.2%), 19 (14.7%) open vascular/aortic cases and 2 cases (1.6%) of percutaneous aortic interventions. Morbidity included rupture (4.7%), stroke (4.7%), paraplegia (8.5%), bowel ischemia (7%), acute renal failure (21%), dialysis requirement (13%), and peripheral ischemia (4.7%). Late vascular-related procedures were performed in 5.2% (6/116) of cases. Univariate risk factors for early mortality were rupture (
P
<0.0001), need for laparotomy (
P
<0.008), acute renal failure (
P
<0.0001), need for dialysis (
P
<0.0001), and lower extremity ischemia (
P
<0.0004). The only independent risk factors for hospital mortality by multiple logistic regression was rupture (
P
<0.0009), and independent risk factors for midterm death were history of chronic obstructive pulmonary disease (
P
<0.002) and low glomerular filtration rate (<57 mL/min;
P
<0.0001).

Conclusions—

Medical management for acute type B aortic dissection is associated acceptable outcomes. Outcomes of other management strategies, eg, endovascular stenting, for acute type B aortic dissection need to be compared with these results.
Integrated Coronary Revascularization
Authors: Katz Marc R. , Van Praet Frank , de Canniere Didier , Murphy Douglas , Siwek Leland , Seshadri-Kreaden Usha , Friedrich Guy , Bonatti Johannes
Published: July 2006

Background—

Robotic totally endoscopic coronary artery bypass (TECAB) of the left anterior descending artery (LAD) coupled with percutaneous coronary intervention (PCI) of a second coronary artery has been investigated in patients with multivessel disease to provide a minimally invasive therapeutic option.

Methods and Results—

TECAB of the LAD was performed using the left internal mammary artery (LIMA). A second lesion was treated with PCI before surgery, simultaneously, or after surgery. Three-month angiographic follow-up was performed in all patients and was subject to independent review. A total of 27 patients requiring double vessel revascularization were treated at 7 centers. Eleven patients underwent PCI before surgery, 12 patients underwent PCI after surgery, and 4 patients underwent simultaneous surgical and percutaneous intervention. Ten patients (37%) were treated with bare metal stents, whereas 17 patients (63%) were treated with drug-eluting stents. Postoperative angiographic evaluation demonstrated an overall LIMA anastomotic patency of 96.3% and PCI vessel patency of 66.7%. There were no deaths or strokes. One patient experienced a perioperative myocardial infarction. Eight of 27 patients (29.6%) required reintervention, 1 LIMA anastomotic stenosis (3.7%), 3 after bare metal stent (30%), and 4 after drug-eluting stent placement (23.5%).

Conclusions—

Integrated revascularization treatment plans provide minimally invasive options for patients with multivessel coronary artery disease. This approach may be accomplished with no mortality, low perioperative morbidity, and excellent angiographic LIMA patency. The reintervention rate after PCI in this series was higher than that reported elsewhere and should be investigated further. The choice of suitable vessel, type of stent and timing of the treatment must be carefully considered before implementing this hybrid strategy.
Synthetic Vascular Prosthesis Impregnated With Mesenchymal Stem Cells Overexpressing Endothelial Nitric Oxide Synthase
Authors: Kanki-Horimoto Sachiko , Horimoto Hitoshi , Mieno Shigetoshi , Kishida Kenji , Watanabe Fusao , Furuya Eisuke , Katsumata Takahiro
Published: July 2006

Background—

Endothelial dysfunction is known to exaggerate coronary artery disease, sometimes leading to irreversible myocardial damage. In such cases, repetitive coronary revascularization including coronary artery bypass grafting is needed, which may cause a shortage of graft conduits. On the other hand, endothelial nitric oxide synthase (eNOS) is an attractive target of cardiovascular gene therapy. The vascular prostheses, of which the inner surfaces are covered with mesenchymal stem cells (MSCs) overexpressing eNOS, are expected to offer feasible effects of NO and angiogenic effects of MSCs on the native coronary arterial beds, as well as improvement of self-patency. Herein, we attempted to develop small caliber vascular prostheses generating the bioactive proteins. Also, we attempted to transduce eNOS cDNA into MSCs.

Methods and Results—

The MSCs were isolated from rat bone marrow and transduced with each adenovirus harboring rat eNOS cDNA and β-galactosidase (β-gal) (eNOS/MSCs and β-gal/MSCs). The β-gal/MSCs were impregnated into vascular prostheses, then the expressions of β-gal on the inner surfaces of them were evaluated by 5-bromo-4-chloro-3-indolyl β-
d
-galactoside staining. The NOS activity of eNOS/MSCs was assayed by monitoring the conversion of
3
H-arginine to
3
H-citrulline. The inner surfaces of the vascular prostheses were covered with MSCs expressing β-gal. The amount of the
3
H-citrulline increased, and eNOS/MSCs were determined to generate enzymatic activity of eNOS. This activity was completely inhibited by
N
G
-nitro-
l
-arginine methyl ester.

Conclusions—

The inner surface of expanded polytetrafluoroethylene vascular prostheses seeded with lacZ gene-transduced MSCs exhibited recombinant proteins. Development of eNOS/MSC-seeded vascular prostheses would promise much longer graft patency and vasculoprotective effects.
Bottom‐Up Life‐Cycle:Assessment of Product Consumption in Belgium
Authors: Jansen Bart , Thollier Karine
Published: July 2006

The present study shows the results and methodology applied to the study of the identification of priority product categories for Belgian product and environmental policy. The main goal of the study was to gather insight into the consumption of products in Belgium and their related life‐cycle environmental impacts. The conclusions of this project on the product categories with major environmental contributions can be used to start up working groups involving stakeholders and initiate detailed product studies on the impact reduction potential that could be achieved by means of implementing product policy measures. Several ways of assessing product category environmental impacts and the effects of policy measures have been developed; ‘bottom‐up’ or ‘market‐life‐cycle assessment’ is one of these, and we tried this approach for the situation in Belgium. Simplified life‐cycle assessment (LCA) studies were conducted for representative average products within each function‐based product category and the results were multiplied with market statistics. Using this approach, we found that building construction, building occupancy, and personal transport are among the major categories for Belgium. The major drawbacks of this approach are the system‐level limitations and the existence of a broad spectrum of nonharmonized methods and datasets from which a sound preliminary selection had to be made. Consequently, the retrieval and selection of data was very time consuming and due to this we had to accept some major limitations in the study design. Nevertheless, the study has contributed to the development of a methodology for market‐LCA and elements that can be picked up in currently ongoing and future work. The study concludes that to improve the feasibility and acceptance of this type of study there is a need for the development of a harmonized methodology on market‐LCA, policy‐relevant impact indicators as well as a harmonized and stakeholder‐agreed‐upon LCA databases.
The Importance of Imports for Household Environmental Impacts
Authors: Peters Glen P. , Hertwich Edgar G.
Published: July 2006

A promising way to reduce environmental impacts of consumer expenditure is through the encouragement of more sustainable consumption patterns. Consumers cause environmental impacts both directly, such as by fuel use in personal cars, and indirectly, by paying for the production of consumables. With increased international trade, the indirect environmental impacts are difficult to determine because a portion of the emissions occurs in different geographical regions. Many previous studies have unrealistically assumed that imports are produced using domestic production technology. For countries with diverging technology and energy mixes the likely errors are significant. This study applies a methodology that explicitly includes technology differences to the case of Norwegian households. It is found that a significant portion of pollution is embodied in Norwegian household imports. Further, a disproportionately large amount of pollution is embodied in imports from developing countries. Overall, as in previous studies, we find that mobility and food are most important in terms of household environmental impacts. By analyzing the imports in more detail we find that for some sectors the majority of emissions occur in foreign regions; in particular, this is true for food, business services, clothing, chemicals, furniture, cars, agriculture, textiles, and most manufactured products.
Conjugality, sexuality and shastras
Authors: Snehi Yogesh
Published: July 2006

Himachal's interaction with colonialism led to the creation of a complex socio-political milieu. Administrative necessities triggered migrations to this region from other parts of Punjab, and brought local customs like reet in contact with the people from the plains. In the 1920s a con-certed campaign began for the abolition of reet. Reet was regarded lewd and an immoral form of marriage, remarriage and divorce. Motivated by the reformist zeal of emulated social reformers, conjugal relations of the locals became a site for contestation. Reformism sought to counter this custom through shastric invalidation, which led to the development of a situation where native hills states and the British government debated, and some of the former enacted rules to abolish this custom. This article tries to evolve a critical understanding of the origins and nature of the debate on the abolition of reet.
Redrawing frontiers
Authors: Misra Sanghamitra
Published: July 2006

The emergence of an Assamese linguistic identity during the late nineteenth and early twentieth century saw its proponents drawing from the colonial linguistic project as well as from indigenous cultural reserves to create a political community that threatened to subsume imagin-ings of smaller regions. This article looks at some of the ways in which resistance to the im-position of a standardised vernacular from Goalpara's traditional elite and the newly-emerging urban intelligentsia transformed language into a symbol for these sections, while also becoming associated with other social roles and group identities. It looks at some of the connections between speech, political culture and economy in the region, focusing on the tensions involved in the relocation of the boundaries of language and the construction of linguistic autonomy, frequently in opposition to both colonial and Assamese nationalist imaginations. It locates these attempts at challenging dominant narratives within the context of both the emergence of a vernacular print culture and a public space, and changes in the material context, in Goalpara and Assam. The article argues that language reflected this material context, and hence reiterates the significance of economic forces in determining discursive practices. Equally importantly, it emphasises the relevance of regional history writing, underscored in this article in the formulation of Rajbansi as the language of a ‘Pranto’ or frontier, for demon-strating larger propositions about the nature of colonial rule.
Does the Effect of Impulsivity on Delinquency Vary by Level of Neighborhood Disadvantage?
Authors: Vazsonyi Alexander T. , Cleveland H. Harrington , Wiebe Richard P.
Published: July 2006

The authors examine the importance of the person-context nexus in adolescent deviance. Using the nationally representative National Longitudinal Study of Adolescent Health (Add Health) data set of more than 20, 000 male and female adolescents, the authors are interested in testing whether the relationship between impulsivity and a variety of deviance measures varies as a function of neighborhood disadvantage. Results suggest that whereas levels of impulsivity and deviance vary by level of neighborhood disadvantage, relationships between impulsivity and deviance do not. This same finding is made for both male and female study participants, though there is some modest evidence of moderation in female youth. Together, these results have important implications for social disorganization theory, the general theory of crime, and for personality research on the etiology of crime and deviance.
Ethical Decision Making for Correctional Mental Health Providers
Authors: Bonner Ron , Vandecreek Leon D.
Published: July 2006

Clinicians who practice correctional mental health care face a number of unique ethical challenges as the result of the correctional environment. Each mental health care profession has a code of ethics to help guide clinicians in practice, but correctional mental health clinicians have sometimes concluded that the ethics codes of their associations provide insufficient guidance for their unique challenges. The American Correctional Health Services Association and the American Association for Correctional and Forensic Psychology have developed codes of ethics, which provide mental health care providers a well-balanced, clinician-derived guide for ethical clinical practice in corrections. These specialized codes complement existing general ethical principles in decision making for correctional mental health providers. The major principles of welfare of the client, informed consent, competence, dual relationships, confidentiality, and social responsibility are reviewed, and case examples are provided to illustrate the ethical decision-making process.
The Effect of Gang Affiliation on Violent Misconduct Among Inmates During the Early Years of Confinement
Authors: Griffin Marie L. , Hepburn John R.
Published: July 2006

The pattern of inmate involvement in violent misconduct is established in the early years of imprisonment, yet few studies have looked at the predictors of violent misconduct during the first months or years of imprisonment, and none have studied the effects of gang affiliation during this time period. This study of 2, 158 male inmates who were confined for at least 3 years in a southwestern state prison system finds that gang affiliation has an effect on violent misconduct among inmates beyond the individual risk factors generally attributed to youth and prior criminal history. These findings suggest the need for additional research to clarify the linkage between gang affiliation and inmate violence, with implications for current efforts to supervise gang-affiliated inmates.
Testing of the SEE and OEE Post–Hip Fracture
Authors: Resnick Barbara , Orwig Denise , Zimmerman Sheryl , Hawkes William , Golden Justine , Werner-Bronzert Michelle , Magaziner Jay
Published: July 2006

The purpose of this study was to test the reliability and validity of the Self-Efficacy for Exercise (SEE) and the Outcome Expectations for Exercise (OEE) scales in a sample of 166 older women post-hip fracture. There was some evidence of validity of the SEE and OEE based on confirmatory factor analysis and Rasch model testing, criterion based and convergent validity, and evidence of internal consistency based on alpha coefficients and separation indices and reliability based on R2 estimates. Rasch model testing demonstrated that some items had high variability. Based on these findings suggestions are made for how items could be revised and the scales improved for future use.
From Our House to the “Big House”: Architectural Design as Visible Metaphor in the School Buildings of Philadelphia
Authors: Thomas George E.
Published: July 2006

Philadelphia public schools have been products of the culture and values that made them. When education was embedded in the home, schools looked like houses; when education became civic, schools took on a civic character; when Philadelphia gave itself over to the forces of industry, schools were derived from industry. In the twentieth century, as schools became places of conflict, they took on the character of the architecture of reform—prisons. This article examines the evolution of the Philadelphia school from the eighteenth century to the present.
The β-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria
Authors: Yadav Mahesh , Schorey Jeffrey S.
Published: July 2006

Pattern recognition receptors (PRRs) play an essential role in a macrophage's response to mycobacterial infections. However, how these receptors work in concert to promote this macrophage response remains unclear. In this study, we used bone marrow–derived macrophages isolated from mannose receptor (MR), complement receptor 3 (CR3), MyD88, Toll-like receptor 4 (TLR4), and TLR2 knockout mice to examine the significance of these receptors in mediating a macrophage's response to a mycobacterial infection. We determined that mitogen-activated protein kinase (MAPK) activation and tumor necrosis factor-α (TNF-α) production in macrophage infected with Mycobacterium avium or M smegmatis is dependent on myeloid differentiation factor 88 (MyD88) and TLR2 but not TLR4, MR, or CR3. Interestingly, the TLR2-mediated production of TNF-α by macrophages infected with M smegmatis required the β-glucan receptor dectin-1. A similar requirement for dectin-1 in TNF-α production was observed for macrophages infected with M bovis Bacillus Calmette-Guerin (BCG), M phlei, M avium 2151-rough, and M tuberculosis H37Ra. The limited production of TNF-α by virulent M avium 724 and M tuberculosis H37Rv was not dependent on dectin-1. Furthermore, dectin-1 facilitated interleukin-6 (IL-6), RANTES (regulated on activation, normal T expressed and secreted), and granulocyte colony-stimulating factor (G-CSF) production by mycobacteria-infected macrophages. These are the first results to establish a significant role for dectin-1, in cooperation with TLR2, to activate a macrophage's proinflammatory response to a mycobacterial infection.
ProtRepeatsDB: a database of amino acid repeats in genomes
Authors: Kalita Mridul K , Ramasamy Gowthaman , Duraisamy Sekhar , Chauhan Virander S , Gupta Dinesh
Published: July 2006

Background

Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB http://bioinfo.icgeb.res.in/repeats/ is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats.

Description

ProtRepeatsDB (v1.2) consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeat s; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology (GO) annotation IDs and regular expressions (REGEXP) describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences.

Conclusion

ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific repeat markers, interspecies variations and polymorphism.
Expression of target and reference genes in Daphnia magna exposed to ibuprofen
Authors: Heckmann Lars-Henrik , Connon Richard , Hutchinson Thomas H , Maund Steve J , Sibly Richard M , Callaghan Amanda
Published: July 2006

Background

Transcriptomic techniques are now being applied in ecotoxicology and toxicology to measure the impact of stressors and develop understanding of mechanisms of toxicity. Microarray technology in particular offers the potential to measure thousands of gene responses simultaneously. However, it is important that microarrays responses should be validated, at least initially, using real-time quantitative polymerase chain reaction (QPCR). The accurate measurement of target gene expression requires normalisation to an invariant internal control e.g., total RNA or reference genes. Reference genes are preferable, as they control for variation inherent in the cDNA synthesis and PCR. However, reference gene expression can vary between tissues and experimental conditions, which makes it crucial to validate them prior to application.

Results

We evaluated 10 candidate reference genes for QPCR in Daphnia magna following a 24 h exposure to the non-steroidal anti-inflammatory drug (NSAID) ibuprofen (IB) at 0, 20, 40 and 80 mg IB l-1. Six of the 10 candidates appeared suitable for use as reference genes. As a robust approach, we used a combination normalisation factor (NF), calculated using the geNorm application, based on the geometric mean of three selected reference genes: glyceraldehyde-3-phosphate dehydrogenase, ubiquitin conjugating enzyme and actin. The effects of normalisation are illustrated using as target gene leukotriene B4 12-hydroxydehydrogenase (Ltb4dh), which was up-regulated following 24 h exposure to 63–81 mg IB l-1.

Conclusions

As anticipated, use of the NF clarified the response of Ltb4dh in daphnids exposed to sublethal levels of ibuprofen. Our findings emphasise the importance in toxicogenomics of finding and applying invariant internal QPCR control(s) relevant to the study conditions.
Incidence trend and risk factors for campylobacterinfections in humans in Norway
Authors: Sandberg Marianne , Nygård Karin , Meldal Hege , Valle Paul Steinar , Kruse Hilde , Skjerve Eystein
Published: July 2006

Background

The objectives of the study were to evaluate whether the increase in incidence of campylobacteriosis observed in humans in Norway from 1995 to 2001 was statistically significant and whether different biologically plausible risk factors were associated with the incidence of campylobacteriosis in the different counties in Norway.

Methods

To model the incidence of domestically acquired campylobacteriosis from 1995 to 2001, a population average random effect poisson model was applied (the trend model). To case data and assumed risk-factor/protective data such as sale of chicken, receiving treated drinking water, density of dogs and grazing animals, occupation of people in the municipalities and climatic factors from 2000 and 2001, an equivalent model accounting for geographical clustering was applied (the ecological model).

Results

The increase in incidence of campylobacteriosis in humans in Norway from 1995 to 2001 was statistically significant from 1998. Treated water was a protective factor against Campylobacter infections in humans with an IRR of 0.78 per percentage increase in people supplied. The two-level modelling technique showed no evidence of clustering of campylobacteriosis in any particular county. Aggregation of data on municipality level makes interpretation of the results at the individual level difficult.

Conclusion

The increase in incidence of Campylobacter infections in humans from 1995 to 2001 was statistically significant from 1998. Treated water was a protective factor against Campylobacter infections in humans with an IRR of 0.78 per percentage increase in people supplied. Campylobacter infections did not appear to be clustered in any particular county in Norway.
Testicular infarction secondary to protein S deficiency: a case report
Authors: McKay Damian , Marron Conor , Brown Robin
Published: July 2006

Background

Protein S deficiency is an inherited cause of thrombophilia. We present the second reported case in the literature of a man developing testicular infarction secondary to protein S deficiency.

Case presentation

A 63 year old man presented with sudden onset of pain in his left hemi-scrotum. Despite oral warfarin therapy the plasma INR was only 1.4 at presentation. Doppler ultrasound scan of the scrotum confirmed absent blood flow to the left testis with increased echogenicity. Orchidectomy was performed to remove the necrotic testis. Post-operatively the patient did well and was referred to the Regional Haemophilia and Thrombosis Centre for further management.

Conclusion

The case highlights a rare but potential complication of protein S deficiency and demonstrates the importance of adequate anticoagulation in these patients.
Comparative genomics of Drosophila and human core promoters
Authors: FitzGerald Peter C , Sturgill David , Shyakhtenko Andrey , Oliver Brian , Vinson Charles
Published: July 2006

Background

The core promoter region plays a critical role in the regulation of eukaryotic gene expression. We have determined the non-random distribution of DNA sequences relative to the transcriptional start site in Drosophila melanogaster promoters to identify sequences that may be biologically significant. We compare these results with those obtained for human promoters.

Results

We determined the distribution of all 65,536 octamer (8-mers) DNA sequences in 10,914 Drosophila promoters and two sets of human promoters aligned relative to the transcriptional start site. In Drosophila, 298 8-mers have highly significant (p ≤ 1 × 10-16) non-random distributions peaking within 100 base-pairs of the transcriptional start site. These sequences were grouped into 15 DNA motifs. Ten motifs, termed directional motifs, occur only on the positive strand while the remaining five motifs, termed non-directional motifs, occur on both strands. The only directional motifs to localize in human promoters are TATA, INR, and DPE. The directional motifs were further subdivided into those precisely positioned relative to the transcriptional start site and those that are positioned more loosely relative to the transcriptional start site. Similar numbers of non-directional motifs were identified in both species and most are different. The genes associated with all 15 DNA motifs, when they occur in the peak, are enriched in specific Gene Ontology categories and show a distinct mRNA expression pattern, suggesting that there is a core promoter code in Drosophila.

Conclusion

Drosophila and human promoters use different DNA sequences to regulate gene expression, supporting the idea that evolution occurs by the modulation of gene regulation.
Treating the World without Leaving Your ED: Opportunities to Deliver Culturally Competent Care
Authors: Sheridan Indrani
Published: July 2006

When asked about cultural sensitivity, well‐meaning, highly educated, and competent physicians admit that while they desire to be culturally sensitive, it is not usually a conscious element of their professional interactions. When it is conscious, they sometimes feel at a disadvantage in their knowledge base or experience. Often physicians are familiar with certain cultural practices but do not know what those practices represent in the lives of their patients; how they produce, exacerbate, or ameliorate illness; and how to function in the patient's best interest within this milieu. In acute clinical encounters, language discordance is by far the most obvious cultural obstacle to providing care. However, increasing exposure to cultural minority populations demonstrates that beyond language, a host of other factors contribute in both obvious and subtle ways to suboptimal care. This report explores some of the challenges faced by immigrant patients and their treating physicians during clinical encounters. It examines the roots of miscommunication and dissatisfaction stemming from cultural differences and expectations and suggests ways to minimize their negative effects.
Asthma Coaching in the Pediatric Emergency Department
Authors: Smith Sharon R. , Jaffe David M. , Highstein Gabrielle , Fisher Edwin B. , Trinkaus Kathryn M. , Strunk Robert C.
Published: July 2006

Objectives:
Coaching and monetary incentives have been used to modify medical behavior of individuals with several chronic diseases, including asthma. The authors performed a randomized, controlled trial of an intervention combining asthma coaching during an emergency department (ED) visit for asthma, and monetary incentive to improve follow‐up with primary care providers (PCP).

Methods:
Subjects were parents of children 2–12 years of age, with Medicaid or no medical insurance, receiving treatment for asthma in the ED. The primary outcome was a verified PCP visit for asthma within two weeks of the index ED visit. All parents received 15 for their time in the ED. Parents in the intervention group were told that they would receive an additional 15 monetary incentive if a PCP visit was completed. The coach engaged in a dialogue with the parent during the ED visit, and discussed the importance and advantages of seeking follow‐up care with the child's PCP. All parents received the usual discharge instructions, including advice to see the PCP within three days.

Results:
The authors enrolled 92 parents; outcome data were available for 86 (42 controls, 50 intervention). Demographic characteristics were similar in both groups. There was no significant difference in the proportion of patients who had follow‐up PCP visits between the intervention (22.0%; 95% confidence interval [95% CI] = 11.5% to 36.0%) and control (23.8%; 95% CI = 12.0% to 39.4%) groups (p = 0.99).

Conclusions:
An intervention combining asthma coaching during acute ED visits and a monetary incentive to return for a PCP visit does not appear to increase follow‐up with the PCP.
Clinical and Economic Factors Associated with Ambulance Use to the Emergency Department
Authors: Ruger Jennifer Prah , Richter Christopher J. , Lewis Lawrence M.
Published: July 2006

Background:
Concern about ambulance diversion and emergency department (ED) overcrowding has increased scrutiny of ambulance use. Knowledge is limited, however, about clinical and economic factors associated with ambulance use compared to other arrival methods.

Objectives:
To compare clinical and economic factors associated with different arrival methods at a large, urban, academic hospital ED.

Methods:
This was a retrospective, cross‐sectional study of all patients seen during 2001 (N= 80,209) at an urban academic hospital ED. Data were obtained from hospital clinical and financial records. Outcomes included acuity and severity level, primary complaint, medical diagnosis, disposition, payment, length of stay, costs, and mode of arrival (bus, car, air‐medical transport, walk‐in, or ambulance). Multivariate logistic regression identified independent factors associated with ambulance use.

Results:
In multivariate analysis, factors associated with ambulance use included: triage acuity A (resuscitation) (adjusted odds ratio [OR], 51.3; 95% confidence interval [CI] = 33.1 to 79.6) or B (emergent) (OR, 9.2; 95% CI = 6.1 to 13.7), Diagnosis Related Group severity level 4 (most severe) (OR, 1.4; 95% CI = 1.2 to 1.8), died (OR, 3.8; 95% CI = 1.5 to 9.0), hospital intensive care unit/operating room admission (OR, 1.9; 95% CI = 1.6 to 2.1), motor vehicle crash (OR, 7.1; 95% CI = 6.4 to 7.9), gunshot/stab wound (OR, 2.1; 95% CI = 1.5 to 2.8), fell 0–10 ft (OR, 2.0; 95% CI = 1.8 to 2.3). Medicaid Traditional (OR, 2.0; 95% CI = 1.4 to 2.4), Medicare Traditional (OR, 1.8; 95% CI = 1.7 to 2.1), arrived weekday midnight–8 AM (OR, 2.0; 95% CI = 1.8 to 2.1), and age ≥65 years (OR, 1.3; 95% CI = 1.2 to 1.5).

Conclusions:
Ambulance use was related to severity of injury or illness, age, arrival time, and payer status. Patients arriving by ambulance were more likely to be acutely sick and severely injured and had longer ED length of stay and higher average costs, but they were less likely to have private managed care or to leave the ED against medical advice, compared to patients arriving by independent means.
Randomized Clinical Trials for Cancer Screening: Rationale and Design Considerations for Imaging Tests
Authors: Black William C.
Published: July 2006

Since the 1960s, there have been revolutionary developments in imaging technology. Undoubtedly, these advances in imaging technology have made it possible to detect most cancers much earlier than they would have presented with clinical signs or symptoms. However, there are harms from screening, including false-positive results and overdiagnosis, and the costs of screening can be substantial. Therefore, screening for cancer must be rigorously evaluated to ensure that it provides more benefit than harm at an acceptable cost. Unfortunately, the evaluation of cancer screening is difficult and susceptible to several forms of bias. Randomized clinical trials are the most valid study design for cancer screening, but they cannot be expected to answer all the questions that arise with the implementation of screening. Decision modeling can be used to extrapolate the results of randomized clinical trials to help inform public policy and individual decision making.
Measures of Response: RECIST, WHO, and New Alternatives
Authors: Jaffe C. Carl
Published: July 2006

RECIST (Response Evaluation Criteria in Solid Tumors) is a widely employed method introduced in 2000 to assess change in tumor size in response to therapy. The simplicity of the technique, however, contrasts sharply with the increasing sophistication of imaging instrumentation. Anatomically based imaging measurement, although supportive of drug development and key to some accelerated drug approvals, is being pressed to improve its methodologic robustness, particularly in the light of more functionally-based imaging that is sensitive to tissue molecular response such as fluorodeoxyglucose positron emission tomography. Nevertheless ready availability of computed tomography and magnetic resonance imaging machines largely assures anatomically based imaging a continuing role in clinical trials for the foreseeable future. Recent advances in image processing enabled by the computational power of modern clinical scanners open a considerable opportunity to characterize tumor response to therapy as a complement to image acquisition. Various alternative quantitative volumetric approaches have been proposed but have yet to gain wide acceptance by clinical and regulatory communities, nor have these more complex techniques shown incontrovertible evidence of greater reproducibility or predictive value of clinical events and outcome. Unless plans are created for clinical trials that incorporate the design needed to prove the added value and unique clinical utility of these novel approaches, any theoretical benefit of these more elaborate methods could remain unfulfilled.
Imaging and Oncologic Drug Development
Authors: El-Deiry Wafik S. , Sigman Caroline C. , Kelloff Gary J.
Published: July 2006

For decades anatomic imaging with computed tomography or magnetic resonance imaging has facilitated drug development in medical oncology by providing quantifiable and objective evidence of response to cancer therapy. In recent years metabolic imaging with [18F]fluorodeoxyglucose–positron emission tomography has added an important component to the oncologist's armamentarium for earlier detection of response that is now widely used and appreciated. These modalities along with ultrasound and optical imaging (bioluminescence, fluorescence, near-infrared imaging, multispectral imaging) have become used increasingly in preclinical studies in animal models to document the effects of genetic alterations on cancer progression or metastases, the detection of minimal residual disease, and response to various therapeutics including radiation, chemotherapy, or biologic agents. The field of molecular imaging offers potential to deliver a variety of probes that can image noninvasively drug targets, drug distribution, cancer gene expression, cell surface receptor or oncoprotein levels, and biomarker predictors of prognosis, therapeutic response, or failure. Some applications are best suited to accelerate preclinical anticancer drug development, whereas other technologies may be directly transferable to the clinic. Efforts are underway to apply noninvasive in vivo imaging to specific preclinical or clinical problems to accelerate progress in the field. Because resources are limited, and patient suffering from failed or ineffective therapy continues, a concerted effort is being made to address these issues. Many simultaneous activities involving academia; the pharmaceutical, device, and biotechnology industries; US Food and Drug Administration; National Cancer Institute; Centers for Medicare and Medicaid Services; and specialized networks sponsored by the National Institutes of Health are beginning to address these issues to develop consensus recommendations and progress in this important area.
Primer on Imaging Technologies for Cancer
Authors: Schnall Mitchell , Rosen Mark
Published: July 2006

Medical images represent maps of the spatial distribution of tissue properties. Each modality probes a specific set of tissue properties such as x-ray attenuation for computed tomography, transmission of sound for ultrasound, and the rate of glucose uptake for fluorodeoxyglucose–positron emission tomography. Understanding the basic principal underlying each modality is important for developing approaches to utilize imaging in cancer research and clinical care. In addition, each modality has specific challenges related to reliable quantitation that are important to appreciate.
Subpopulations of Corticotrophs in the Sheep Pituitary during Late Gestation: Effects of Development and Placental Restriction
Authors: Farrand Kirsten , McMillen I. Caroline , Tanaka Shigeyasu , Schwartz Jeffrey
Published: July 2006

The prepartum surge in fetal plasma cortisol is essential for the normal timing of parturition in sheep and may result from an increase in the ratio of ACTH to proopiomelanocortin (POMC) in the fetal circulation. In fetuses subjected to experimental induction of placental restriction, the prepartum surge in fetal cortisol is exaggerated, whereas pituitary POMC mRNA levels are decreased, and in vitro, unstimulated ACTH secretion is elevated in corticotrophs nonresponsive to CRH. We therefore investigated the changes in the relative proportions of cells expressing POMC, ACTH, and the CRH type 1 receptor (CRHR1) shortly before birth and during chronic placental insufficiency. Placental restriction (PR) was induced by removal of the majority of placental attachment sites in five ewes before mating. Pituitaries were collected from control and PR fetal sheep at 140 d (control, n = 4; PR, n = 4) and 144 d (control, n = 6; PR, n = 4). Pituitary sections were labeled with specific antisera raised against POMC, ACTH, and CRHR1. Three major subpopulations of corticotrophs were identified that expressed POMC + ACTH + CRHR1, ACTH + CRHR1, or POMC only. The proportion of pituitary corticotrophs expressing POMC + ACTH + CRHR1 decreased (P < 0.05) between 140 (control, 60 ± 1%; PR, 66 ± 4%) and 144 (control, 45 ± 2%; PR, 56 ± 6%) d. A significantly higher (P < 0.05) proportion of corticotrophs expressed POMC + ACTH + CRHR1 in the pituitary of the PR group compared with controls. This study is the first to demonstrate subpopulations of corticotrophs in the fetal sheep pituitary that differentially express POMC, ACTH, and CRHR1 and the separate effects of gestational age and placental restriction on these subpopulations of corticotrophs.