bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnesium Deficiency in Critical Illness
Authors: Tong Garrison M. , Rude Robert K.
Published: January 2005

Magnesium (Mg) deficiency commonly occurs in critical illness and correlates with a higher mortality and worse clinical outcome in the intensive care unit (ICU). Magnesium has been directly implicated in hypokalemia, hypocalcemia, tetany, and dysrhythmia. Moreover, Mg may play a role in acute coronary syndromes, acute cerebral ischemia, and asthma. Magnesium regulates hundreds of enzyme systems. By regulating enzymes controlling intracellular calcium, Mg affects smooth muscle vasoconstriction, important to the underlying pathophysiology of several critical illnesses. The principle causes of Mg deficiency are gastrointestinal and renal losses; however, the diagnosis is difficult to make because of the limitations of serum Mg levels, the most common assessment of Mg status. Magnesium tolerance testing and ionized Mg2+ are alternative laboratory assessments; however, each has its own difficulties in the ICU setting. The use of Mg therapy is supported by clinical trials in the treatment of symptomatic hypomagnesemia and preeclampsia and is recommended for torsade de pointes. Magnesium therapy is not supported in the treatment of acute myocardial infarction and is presently undergoing evaluation for the treatment of severe asthma exacerbation, for the prevention of postcoronary bypass grafting dysrhythmias, and as a neuroprotective agent in acute cerebral ischemia.
Acute Effects of Upright Position on Gas Exchange in Patients With Acute Respiratory Distress Syndrome
Authors: Hoste Eric A. J. , Roosens Carl D. V. K. , Bracke Steven , Decruyenaere Johan M. A. , Benoit Dominique D. , Vandewoude Koenraad H. D. K. , Colardyn Francis A.
Published: January 2005

Patients with acute respiratory distress syndrome (ARDS) have dorsal atelectasis of the lungs. This is probably caused by several mechanisms: compression on dependent lung zones, purulent secretions in alveoli, and upward shift of the diaphragm. An upright position (UP) of the patient (the whole body in a straight line at 40 to 45 degrees) can theoretically ameliorate these mechanisms. The objective was to evaluate whether there was an improvement of gas exchange during UP of ARDS patients and to evaluate the hemodynamic effects. A prospective interventional study was performed in the surgical and medical ICUs and the burn unit of the Ghent University Hospital, a tertiary care center. Included were ARDS patients with onset of ARDS within 48 hours before start of the study. Patients were excluded when there was hemodynamic instability or when the PaO2/FiO2 ratio deteriorated during the 2 hours preceding UP. After a 2-hour observation period in a semirecumbent position, patients were put in UP for 12 hours. Respiration and hemodynamic data were recorded at the start and end of the 2-hour observation period, and after 1, 4, and 12 hours in UP. Eighteen patients were included in the study. There was a significant increase of the PaO2/FiO2 ratio during UP ( P< .001). Except for the need for volume resuscitation in 5 patients (27.8%), there was no significant change in the hemodynamic profile of the patients. Upright positioning of patients with ARDS, a relatively simple maneuver, resulted in an improvement of gas exchange and was tolerated hemodynamically relatively well during a 12-hour observation period.
A Prospective Multicenter Study to Evaluate the Feasibility and Safety of Aggressive Antihypertensive Treatment in Patients With Acute Intracerebral Hemorrhage
Authors: Qureshi Adnan I. , Mohammad Yousef M. , Yahia Abutaher M. , Suarez Jose I. , Siddiqui Amir M. , Kirmani Jawad F. , Suri M. Fareed K. , Kolb James , Zaidat Osama O.
Published: January 2005

The authors performed a multicenter prospective observational study to evaluate the feasibility and safety of intravenous antihypertensive protocol for acute hypertension in patients with intracerebral hemorrhage (ICH). Twentyseven patients with ICH and acute hypertension (mean age 61.37 ± 14.27; 10 were men) were treated to maintain the systolic blood pressure (BP) below 160 mm Hg and diastolic BP below 90 mm Hg within 24 hours of symptom onset. Neurological deterioration (defined as a decrease in initial Glasgow Coma Scale score= 2) was observed in 2 (7.4%) of 27 patients during treatment. Among patients who underwent follow-up computed tomography, hematoma expansion (more than 33% increase in hematoma size at 24 hours) was observed in 2 (9.1%) of 22 patients. Patients treated within 6 hours of symptom onset were more likely to be functionally independent (modified Rankin scale–= 2) at 1 month compared with patients who were treated between 6 and 24 hours (8 of 18 versus 0 of 9, P= .03). Aggressive pharmacological treatment of acute hypertension in patients with ICH can be initiated early with a low rate of neurological deterioration and hematoma expansion.
Attributes of Spiritual Care in Nursing Practice
Authors: Sawatzky Rick , Pesut Barbara
Published: January 2005

Nurses are increasingly being called on to engage in spiritual care with their patients. A diverse body of theoretical and empirical literature addresses spirituality as it relates to nursing practice, yet there is little consensus about what spiritual nursing care entails. The purpose of this article is to conceptualize spiritual care in relation to nursing practice. A brief historical review indicates that our current understandings of spiritual nursing care have been shaped by three eras characterized by particular approaches: the religious approach, the scientific approach, and the existential approach. We draw elements from each of these approaches to propose attributes of spiritual care in the context of nursing practice. We propose that spiritual nursing care is an intuitive, interpersonal, altruistic, and integrative expression that is contingent on the nurse’s awareness of the transcendent dimension of life but that reflects the patient’s reality.
Navigating the Journey to Menses Cessation
Authors: Matarese Colette J.
Published: January 2005

Purpose: This article explores contemporary women’s perceptions of the experience of the menopausal process within the Western industrialized culture, describes and synthesizes the processes used by women to evaluate available information, and explores and facilitates processes used by women to envision and create change in their life world. Method: An emancipatory group process was designed to facilitate dialogue between the investigator and nine women who met as a group eight times during a 10-week period in the home of one of the participants. Findings: Participants identified menses cessation as a time of change in all aspects of their lives. They employed decision making to cope with these changes and, as a result of the awareness that came through the research process, invited other women to celebrate the collective wisdom of women at all stages of life. Conclusion: Women experiencing menses cessation need information and time to process that information internally and in relation with others. Implications: Nurses can facilitate the process by providing knowledge, assisting women in decision making, and intervening in ways that contribute to a holistic quality of life for women.
Development and Preliminary Evaluation of the Existential Meaning Scale
Authors: Lyon Debra E. , Younger Janet
Published: January 2005

Purpose: The aim of this study was to develop and examine the psychometric properties of the Existential Meaning Scale (EMS). Findings: Construct validity of the EMS was examined through factor analysis and correlational analyses with theoretically related instruments. After several weak items were deleted, the 20-item scale had a Cronbach’s alpha coefficient of > .80 in an overall sample of 418 individuals. Scores on the EMS were significantly lower in a sample of persons with HIV-1 infection than in the general population samples. Conclusion: Although its initial psychometric properties were satisfactory, additional validation of the EMS is necessary in other clinical populations to examine further the psychometric properties of the EMS. In addition, further examination of the responsiveness of the EMS over time is needed to evaluate its potential utility in longitudinal trials.
Lip Service to Multiculturalism
Authors: Hoobler Jenny M.
Published: January 2005

Troubled by the superficiality of most organizational efforts designed to embrace multi-culturalism, the author argues that despite the substantial allocation of resources, the quest for multiculturalism has amounted to little real organizational change. Foucault’s theory of “docile bodies” (1995) is used to illustrate that true multiculturalism is an improbable goal when paired with the extant view of efficiency and authority in modern organizations.
Reflections on Two Views of Managing Learning and Knowledge in Organizations
Authors: Argote Linda
Published: January 2005

The commentary reflects on two essays on managing learning and knowledge in organizations. The essay on organizational learning was written by Friedman, Lipshitz, and Popper; the essay on knowledge management was written by Hazlett, McAdam, and Gallagher. Key points in the two essays are highlighted and points of convergence discussed. Opportunities for future work on organizational learning and knowledge management are identified.
Theory Building in Knowledge Management
Authors: Hazlett Shirley-Ann , McAdam Rodney , Gallagher Séamus
Published: January 2005

The development of knowledge management (KM) in theory and praxis continues to involve a wide range of disciplines and contributors, each bringing their respective experiences, beliefs, and practices. Two of the main disciplines that contribute to the KM discourse are information systems and management. However, this study of KM has revealed an apparent dichotomy between those researchers from an information systems background and those from a management background. Approaches and models based on each perspective have emerged, but there is little evidence of synergy and convergence. This article shows that attempts to develop an optimal KM methodology are misplaced unless the underlying assumptions and paradigms are identified and understood. Furthermore, it is proposed that KM is currently in a state of “pre-science,” wherein proponents of different paradigms have their own beliefs and values and often disagree with others about fundamentals within the field.
The Mystification of Organizational Learning
Authors: Friedman Victor J. , Lipshitz Raanan , Popper Micha
Published: January 2005

Despite the growing popularity of organizational learning and the proliferation of literature on the subject, the concept remains elusive for researchers and managers alike. This article argues that enduring uncertainty about the meaning and practice of organizational learning reflects its so-called mystification. It attributes mystification to five features of the field: (a) ever-increasing conceptual diversity, (b) anthropomorphizing organizational learning, (c) a split in the field between visionaries and skeptics, (d) the reification of terminology, and (e) active mystification of the concept. The article explains and illustrates how the literature on organizational learning has contributed to these processes of mystification. It concludes by specifying a number of strategies that researchers and practitioners can employ to demystify the concept of organizational learning.
We (Still) Need a World of Scholar-Leaders
Authors: Ritchie J. B. , Hammond Scott C.
Published: January 2005

In this article, the authors argue that management education has been corrupted by a “down loading” metaphor of learning that has created a culture of mediocrity. They argue that students should become scholars; that learning has inherent value, that discovery and critical thinking are essential for the leaders of tomorrow. The authors argue that students acting as scholars should not rely on organizations for direction, but should assume responsibility for making organizations havens for self-responsibility. This article is widely used to launch a discussion about student responsibility.
Inhibition of TNFalpha in vivo prevents hyperoxia-mediated activation of caspase 3 in type II cells
Authors: Guthmann Florian , Wissel Heide , Schachtrup Christian , Tölle Angelika , Rüdiger Mario , Spener Friedrich , Rüstow Bernd
Published: January 2005

Background

The mechanisms during the initial phase of oxygen toxicity leading to pulmonary tissue damage are incompletely known. Increase of tumour necrosis factor alpha (TNFalpha) represents one of the first pulmonary responses to hyperoxia. We hypothesised that, in the initial phase of hyperoxia, TNFalpha activates the caspase cascade in type II pneumocytes (TIIcells).

Methods

Lung sections or freshly isolated TIIcells of control and hyperoxic treated rats (48 hrs) were used for the determination of TNFalpha (ELISA), TNF-receptor 1 (Western blot) and activity of caspases 8, 3, and 9 (colorimetrically). NF-kappaB activation was determined by EMSA, by increase of the p65 subunit in the nuclear fraction, and by immunocytochemistry using a monoclonal anti-NF-kappaB-antibody which selectively stained the activated, nuclear form of NF-kappa B. Apoptotic markers in lung tissue sections (TUNEL) and in TIIcells (cell death detection ELISA, Bax, Bcl-2, mitochondrial membrane potential, and late and early apoptotic cells) were measured using commercially available kits.

Results

In vivo, hyperoxia activated NF-kappaB and increased the expression of TNFalpha, TNF-receptor 1 and the activity of caspase 8 and 3 in freshly isolated TIIcells. Intratracheal application of anti-TNFalpha antibodies prevented the increase of TNFRI and of caspase 3 activity. Under hyperoxia, there was neither a significant change of cytosolic cytochrome C or of caspase 9 activity, nor an increase in apoptosis of TIIcells. Hyperoxia-induced activation of caspase 3 gradually decreased over two days of normoxia without increasing apoptosis. Therefore, activation of caspase 3 is a temporary effect in sublethal hyperoxia and did not mark the "point of no return" in TIIcells.

Conclusion

In the initiation phase of pulmonary oxygen toxicity, an increase of TNFalpha and its receptor TNFR1 leads to the activation of caspase 8 and 3 in TIIcells. Together with the hyperoxic induced increase of Bax and the decrease of the mitochondrial membrane potential, activation of caspase 3 can be seen as sensitisation for apoptosis. Eliminating the TNFalpha effect in vivo by anti-TNFalpha antibodies prevents the pro-apoptotic sensitisation of TIIcells.
The absence of reactive oxygen species production protects mice against bleomycin-induced pulmonary fibrosis
Authors: Manoury Boris , Nenan Soazig , Leclerc Olivier , Guenon Isabelle , Boichot Elisabeth , Planquois Jean-Michel , Bertrand Claude P , Lagente Vincent
Published: January 2005

Background

Reactive oxygen species and tissue remodeling regulators, such as metalloproteinases (MMPs) and their inhibitors (TIMPs), are thought to be involved in the development of pulmonary fibrosis. We investigated these factors in the fibrotic response to bleomycin of p47phox -/- (KO) mice, deficient for ROS production through the NADPH-oxidase pathway.

Methods

Mice are administered by intranasal instillation of 0.1 mg bleomycin. Either 24 h or 14 days after, mice were anesthetized and underwent either bronchoalveolar lavage (BAL) or lung removal.

Results

BAL cells from bleomycin treated WT mice showed enhanced ROS production after PMA stimulation, whereas no change was observed with BAL cells from p47phox -/- mice. At day 1, the bleomycin-induced acute inflammatory response (increased neutrophil count and MMP-9 activity in the BAL fluid) was strikingly greater in KO than wild-type (WT) mice, while IL-6 levels increased significantly more in the latter. Hydroxyproline assays in the lung tissue 14 days after bleomycin administration revealed the absence of collagen deposition in the lungs of the KO mice, which had significantly lower hydroxyproline levels than the WT mice. The MMP-9/TIMP-1 ratio did not change at day 1 after bleomycin administration in WT mice, but increased significantly in the KO mice. By day 14, the ratio fell significantly from baseline in both strains, but more in the WT than KO strains.

Conclusions

These results suggest that NADPH-oxidase-derived ROS are essential to the development of pulmonary fibrosis. The absence of collagen deposition in KO mice seems to be associated with an elevated MMP-9/TIMP-1 ratio in the lungs. This finding highlights the importance of metalloproteinases and protease/anti-protease imbalances in pulmonary fibrosis.
A robust two-way semi-linear model for normalization of cDNA microarray data
Authors: Wang Deli , Huang Jian , Xie Hehuang , Manzella Liliana , Soares Marcelo Bento
Published: January 2005

Background

Normalization is a basic step in microarray data analysis. A proper normalization procedure ensures that the intensity ratios provide meaningful measures of relative expression values.

Methods

We propose a robust semiparametric method in a two-way semi-linear model (TW-SLM) for normalization of cDNA microarray data. This method does not make the usual assumptions underlying some of the existing methods. For example, it does not assume that: (i) the percentage of differentially expressed genes is small; or (ii) the numbers of up- and down-regulated genes are about the same, as required in the LOWESS normalization method. We conduct simulation studies to evaluate the proposed method and use a real data set from a specially designed microarray experiment to compare the performance of the proposed method with that of the LOWESS normalization approach.

Results

The simulation results show that the proposed method performs better than the LOWESS normalization method in terms of mean square errors for estimated gene effects. The results of analysis of the real data set also show that the proposed method yields more consistent results between the direct and the indirect comparisons and also can detect more differentially expressed genes than the LOWESS method.

Conclusions

Our simulation studies and the real data example indicate that the proposed robust TW-SLM method works at least as well as the LOWESS method and works better when the underlying assumptions for the LOWESS method are not satisfied. Therefore, it is a powerful alternative to the existing normalization methods.
Inference of demographic history from genealogical trees using reversible jump Markov chain Monte Carlo
Authors: Opgen-Rhein Rainer , Fahrmeir Ludwig , Strimmer Korbinian
Published: January 2005

Background

Coalescent theory is a general framework to model genetic variation in a population. Specifically, it allows inference about population parameters from sampled DNA sequences. However, most currently employed variants of coalescent theory only consider very simple demographic scenarios of population size changes, such as exponential growth.

Results

Here we develop a coalescent approach that allows Bayesian non-parametric estimation of the demographic history using genealogies reconstructed from sampled DNA sequences. In this framework inference and model selection is done using reversible jump Markov chain Monte Carlo (MCMC). This method is computationally efficient and overcomes the limitations of related non-parametric approaches such as the skyline plot. We validate the approach using simulated data. Subsequently, we reanalyze HIV-1 sequence data from Central Africa and Hepatitis C virus (HCV) data from Egypt.

Conclusions

The new method provides a Bayesian procedure for non-parametric estimation of the demographic history. By construction it additionally provides confidence limits and may be used jointly with other MCMC-based coalescent approaches.
Brainstem levels of transcription factor AP-2 in rat are changed after treatment with phenelzine, but not with citalopram
Authors: Berggard Cecilia , Damberg Mattias , Oreland Lars
Published: January 2005

Background

Before therapeutic effect is obtained after treatment with antidepressant drugs, like serotonin selective reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAO-Is) there is an initial lag-period of a few weeks. Neuronal adaptations on a molecular level are supposed to be involved in the initiation of the antidepressant effect. Transcription factor AP-2 is essential for neuronal development and many genes involved in the brainstem monoaminergic systems have binding sites for AP-2 in their regulatory regions. The genotype of the AP-2β isoform has been associated with e.g. anxiety-related personality traits and with platelet MAO activity. In addition, previous studies have shown that the levels of AP-2α and AP-2β in rat whole brain were decreased after 10 days of treatment with citalopram (SSRI) and imipramine (TCA), and were increased with phenelzine (MAO-I).

Results

In the present study, we report that treatment with citalopram for 1, 7 or 21 days did not have effect on the AP-2 levels in rat brainstem. However, after treatment with phenelzine for 1, 7 or 21 days the levels of AP-2α and AP-2β had increased after 7 days, but had returned to control levels at day 21.

Conclusion

The decrease in AP-2 levels in rat whole brain previously seen after treatment with citalopram does not seem to be localised to the brainstem, it may rather occur in the monoaminergic terminal projection areas. The present data suggest that the increase in AP-2 levels previously seen in rat whole brain after subchronic treatment with phenelzine is located in the brainstem. It cannot, however, be excluded that other brain regions are involved.
Factors influencing emergency medical readmission risk in a UK district general hospital: A prospective study
Authors: Lyratzopoulos Georgios , Havely Daniel , Gemmell Islay , Cook Gary A
Published: January 2005

Background

Over recent years increased emphasis has been given to performance monitoring of NHS hospitals, including overall number of hospital readmissions, which however are often sub-optimally adjusted for case-mix. We therefore conducted a study to examine the effect of various patient and disease factors on the risk of emergency medical readmission.

Methods

The study setting was a District General Hospital in Greater Manchester and the study period was 4.5-years. All index emergency medical admission during the study period leading to a live discharge were included in the study (n = 20,209). A multivariable proportional hazards modelling was used, based on Hospital Episodes Statistics data, to examine the influence of various baseline factors on readmission risk. Deprivation status was measured with the Townsend deprivation index score. Hazard ratios (HR) and associated 95% confidence intervals (CI) of unplanned emergency medical admission by sex, age group, admission method, diagnostic group, number of coded co-morbidities, length of stay and patient's deprivation status quartile, were calculated.

Results

Significant independent predictors of readmission risk at 12 months were male sex (HR 1.13, CI: 1.07–1.2), age (age >75 (HR 1.57, CI 1.45–1.7), number of coded co-morbidities (HR for >4 coded co-morbidities: 1.49 CI: 1.26–1.76), admission via GP referral (HR 0.93, CI 0.88–0.99) and primary diagnosis of heart failure (HR 1.33, CI: 1.16–1.53) and chronic obstructive pulmonary disease/asthma (HR 1.34, CI: 1.21–1.48). Higher level of deprivation was also significantly and independently associated and with increased emergency medical readmission risk at three (HR for the most deprived quartile 1.21, CI: 1.08–1.35), six (HR 1.21, CI: 1.1–1.33) and twelve months (HR 1.25, CI: 1.16–1.36).

Conclusions

There is a potential for improving health and reducing demand for emergency medical admissions with more effective management of patients with heart failure and chronic obstructive airways disease/asthma. There is also a potential for improving health and reducing demand if reasons for increased readmission risk in more deprived patients are understood. The potential influence of deprivation status on readmission risk should be acknowledged, and NHS performance indicators adjustment for deprivation case-mix would be prudent.
Towards an understanding of barriers to condom use in rural Benin using the Health Belief Model: A cross sectional survey
Authors: Hounton Sennen H , Carabin Hélène , Henderson Neil J
Published: January 2005

Background

HIV/AIDS is the most dramatic epidemic of the century that has claimed over two decade more than 3 million deaths. Sub Saharan Africa is heavily affected and accounts for nearly 70% of all cases. Despite awareness campaigns, prevention measures and more recently promotion of anti viral regimens, the prevalence of cases and deaths is still rising and the prevalence of systematic condom use remains low, especially in rural areas. This study identifies barriers to condom use based on the Health Belief Model (HBM) in Benin, West Africa.

Methods

The study was a cross-sectional survey conducted from June to July 2002. Two hundred fifty one (251) individuals were interviewed using a structured questionnaire adapted from a standardized WHO/GAP questionnaire. A logistic regression was used to identify factors associated with condom use.

Results

In spite of satisfactory knowledge on HIV/AIDS transmission, participants are still at high risk of contracting the infection. Sixty three (63) percents of the interviewees reported being able to recognize infected people, and condom use during the last occasional intercourse was declared by only 36.8% of males and 47.5% of females. Based on the HBM, failure to use condom was related to its perceived lack of efficacy [OR = 9.76 (3.71–30.0)] and perceived quality [OR = 3.61 (1.31–9.91)].

Conclusions

This study identifies perceived efficacy (incomplete protective effect) and perceived utilization-related problem (any reported problem using condoms) as the main barriers to condom use. Hence, preventions strategies based on increasing perceived risk, perceived severity or adequate knowledge about HIV/AIDS may not be sufficient to induce condom use. These data will be useful in designing and improving HIV/AIDS prevention outreach programs in Sub Saharan Africa.
Molecular models of NS3 protease variants of the Hepatitis C virus
Authors: da Silveira Nelson JF , Arcuri Helen A , Bonalumi Carlos E , de Souza Fátima P , Mello Isabel MVGC , Rahal Paula , Pinho João RR , de Azevedo Walter F
Published: January 2005

Background

Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed.

Results

The atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures.

Conclusions

This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure-based drug design of a new generation of NS3 protease variants inhibitors. All models in the database are publicly accessible via our interactive website, providing us with large amount of structural models for use in protein-ligand docking analysis.
Histopathological changes in the human larynx following expanded polytetrafluroethylene (Gore-Tex®) implantation
Authors: Rajkumar K , Khalil HS , Elloy M , Sheffield E , Baldwin DL
Published: January 2005

Background

Expanded polytetrafluroethelyne (e PTFE, Gore-Tex®) has been advocated as an implant material for medialization of the vocal fold. Animal studies involving rabbits and a porcine model have demonstrated host tolerance of the implant. There have been no reports describing the histological changes in a human laryngectomy specimen with a Gore-Tex implant.

Case presentation

The histological findings in a laryngectomy specimen of a patient previously implanted with e PTFE for medialization of a paralyzed vocal fold following excision of a vagal neurofibroma were studied.

Histopathology revealed a mild foreign-body giant cell granulomatous reaction with some associated fibrosis. The granulomatous response was limited to the periphery of the Gore-Tex and although it closely followed the profile of the material it did not encroach into or significantly break up the material. There was no significant neutrophilic or lymphocytic inflammation.

Conclusions

Our findings are consistent with the animal models confirming that Gore-Tex implantation does not result in a significant granulomatous reaction in the human larynx over a 13-month period. Moreover, there is no evidence of resorption or infection. Further, the lack of lymphocytes in association with the granulomas indicates that there is no significant immunological hypersensitivity. Histologically, the slight permeation by connective tissue is similar to that seen in Gore-Tex vascular and cardiac implants. The degree of the slight giant cell response appears to be dependent on the profile of the material; a sharp edge incited more of a response than a flat surface.
What do hospital decision-makers in Ontario, Canada, have to say about the fairness of priority setting in their institutions?
Authors: Reeleder David , Martin Douglas K , Keresztes Christian , Singer Peter A
Published: January 2005

Background

Priority setting, also known as rationing or resource allocation, occurs at all levels of every health care system. Daniels and Sabin have proposed a framework for priority setting in health care institutions called 'accountability for reasonableness', which links priority setting to theories of democratic deliberation. Fairness is a key goal of priority setting. According to 'accountability for reasonableness', health care institutions engaged in priority setting have a claim to fairness if they satisfy four conditions of relevance, publicity, appeals/revision, and enforcement. This is the first study which has surveyed the views of hospital decision makers throughout an entire health system about the fairness of priority setting in their institutions. The purpose of this study is to elicit hospital decision-makers' self-report of the fairness of priority setting in their hospitals using an explicit conceptual framework, 'accountability for reasonableness'.

Methods

160 Ontario hospital Chief Executive Officers, or their designates, were asked to complete a survey questionnaire concerning priority setting in their publicly funded institutions. Eight-six Ontario hospitals completed this survey, for a response rate of 54%. Six close-ended rating scale questions (e.g. Overall, how fair is priority setting at your hospital?), and 3 open-ended questions (e.g. What do you see as the goal(s) of priority setting in your hospital?) were used.

Results

Overall, 60.7% of respondents indicated their hospitals' priority setting was fair. With respect to the 'accountability for reasonableness' conditions, respondents indicated their hospitals performed best for the relevance (75.0%) condition, followed by appeals/revision (56.6%), publicity (56.0%), and enforcement (39.5%).

Conclusions

For the first time hospital Chief Executive Officers within an entire health system were surveyed about the fairness of priority setting practices in their institutions using the conceptual framework 'accountability for reasonableness'. Although many hospital CEOs felt that their priority setting was fair, ample room for improvement was noted, especially for the enforcement condition.
An online operational rainfall-monitoring resource for epidemic malaria early warning systems in Africa
Authors: Grover-Kopec Emily , Kawano Mika , Klaver Robert W , Blumenthal Benno , Ceccato Pietro , Connor Stephen J
Published: January 2005

Periodic epidemics of malaria are a major public health problem for many sub-Saharan African countries. Populations in epidemic prone areas have a poorly developed immunity to malaria and the disease remains life threatening to all age groups. The impact of epidemics could be minimized by prediction and improved prevention through timely vector control and deployment of appropriate drugs. Malaria Early Warning Systems are advocated as a means of improving the opportunity for preparedness and timely response.

Rainfall is one of the major factors triggering epidemics in warm semi-arid and desert-fringe areas. Explosive epidemics often occur in these regions after excessive rains and, where these follow periods of drought and poor food security, can be especially severe. Consequently, rainfall monitoring forms one of the essential elements for the development of integrated Malaria Early Warning Systems for sub-Saharan Africa, as outlined by the World Health Organization.

The Roll Back Malaria Technical Resource Network on Prevention and Control of Epidemics recommended that a simple indicator of changes in epidemic risk in regions of marginal transmission, consisting primarily of rainfall anomaly maps, could provide immediate benefit to early warning efforts. In response to these recommendations, the Famine Early Warning Systems Network produced maps that combine information about dekadal rainfall anomalies, and epidemic malaria risk, available via their Africa Data Dissemination Service. These maps were later made available in a format that is directly compatible with HealthMapper, the mapping and surveillance software developed by the WHO's Communicable Disease Surveillance and Response Department. A new monitoring interface has recently been developed at the International Research Institute for Climate Prediction (IRI) that enables the user to gain a more contextual perspective of the current rainfall estimates by comparing them to previous seasons and climatological averages. These resources are available at no cost to the user and are updated on a routine basis.
Asthma is a risk factor for acute chest syndrome and cerebral vascular accidents in children with sickle cell disease
Authors: Nordness Mark E , Lynn John , Zacharisen Michael C , Scott Paul J , Kelly Kevin J
Published: January 2005

Background

Asthma and sickle cell disease are common conditions that both may result in pulmonary complications. We hypothesized that children with sickle cell disease with concomitant asthma have an increased incidence of vaso-occlusive crises that are complicated by episodes of acute chest syndrome.

Methods

A 5-year retrospective chart analysis was performed investigating 48 children ages 3–18 years with asthma and sickle cell disease and 48 children with sickle cell disease alone. Children were matched for age, gender, and type of sickle cell defect. Hospital admissions were recorded for acute chest syndrome, cerebral vascular accident, vaso-occlusive pain crises, and blood transfusions (total, exchange and chronic). Mann-Whitney test and Chi square analysis were used to assess differences between the groups.

Results

Children with sickle cell disease and asthma had significantly more episodes of acute chest syndrome (p = 0.03) and cerebral vascular accidents (p = 0.05) compared to children with sickle cell disease without asthma. As expected, these children received more total blood transfusions (p = 0.01) and chronic transfusions (p = 0.04). Admissions for vasoocclusive pain crises and exchange transfusions were not statistically different between cases and controls. SS disease is more severe than SC disease.

Conclusions

Children with concomitant asthma and sickle cell disease have increased episodes of acute chest syndrome, cerebral vascular accidents and the need for blood transfusions. Whether aggressive asthma therapy can reduce these complications in this subset of children is unknown and requires further studies.
Harnessing genomics to improve health in the Eastern Mediterranean Region – an executive course in genomics policy
Authors: Acharya Tara , Rab Mohammed Abdur , Singer Peter A , Daar Abdallah S
Published: January 2005

Background

While innovations in medicine, science and technology have resulted in improved health and quality of life for many people, the benefits of modern medicine continue to elude millions of people in many parts of the world. To assess the potential of genomics to address health needs in EMR, the World Health Organization's Eastern Mediterranean Regional Office and the University of Toronto Joint Centre for Bioethics jointly organized a Genomics and Public Health Policy Executive Course, held September 20th–23rd, 2003, in Muscat, Oman. The 4-day course was sponsored by WHO-EMRO with additional support from the Canadian Program in Genomics and Global Health. The overall objective of the course was to collectively explore how to best harness genomics to improve health in the region. This article presents the course findings and recommendations for genomics policy in EMR.

Methods

The course brought together senior representatives from academia, biotechnology companies, regulatory bodies, media, voluntary, and legal organizations to engage in discussion. Topics covered included scientific advances in genomics, followed by innovations in business models, public sector perspectives, ethics, legal issues and national innovation systems.

Results

A set of recommendations, summarized below, was formulated for the Regional Office, the Member States and for individuals.

• Advocacy for genomics and biotechnology for political leadership;

• Networking between member states to share information, expertise, training, and regional cooperation in biotechnology; coordination of national surveys for assessment of health biotechnology innovation systems, science capacity, government policies, legislation and regulations, intellectual property policies, private sector activity;

• Creation in each member country of an effective National Body on genomics, biotechnology and health to:

- formulate national biotechnology strategies

- raise biotechnology awareness

- encourage teaching and training of biotechnology

- devise integration of biotechnology within national health systems.

Conclusion

The recommendations provide the basis for a road map for EMR to take steps to harness biotechnology for better and more equitable health. As a result of these recommendations, health ministers from the region, at the 50th Regional Committee Meeting held in October 2003, have urged Member States to establish national bodies of biotechnology to formulate a strategic vision for developing biotechnology in the service of the region's health. These efforts promise to raise the profile of genomics in EMR and increase regional cooperation in this exciting new field.
Balance between survivin, a key member of the apoptosis inhibitor family, and its specific antibodies determines erosivity in rheumatoid arthritis
Authors: Bokarewa Maria , Lindblad Sofia , Bokarew Dmitriy , Tarkowski Andrej
Published: January 2005

Rheumatoid arthritis (RA) is a highly heterogeneous disease with respect to its joint destructivity. The reasons underlying this heterogeneity are unknown. Deficient apoptosis in rheumatoid synovial tissue has been recently demonstrated. We have therefore decided to study the synovial expression of survivin, a key member of the apoptosis inhibitor family. The levels of survivin and antibodies against survivin were assessed by an ELISA in matched blood and synovial fluid samples collected from 131 RA patients. Results were related to joint erosivity at the time of sampling. Monocytes were transfected with survivin anti-sense oligonucleotides and were assessed for their ability to produce inflammatory cytokines. Survivin levels were significantly higher in patients with destructive disease as compared with in RA patients displaying a non-erosive disease. High survivin levels were an independent prognostic parameter for erosive RA. In contrast, high levels of antibodies against survivin were found in patients with non-erosive RA, and were negatively related to erosivity. Survivin levels in RA patients were influenced by treatment, being significantly lower among patients treated with disease-modifying anti-rheumatic drugs. Specific suppression of survivin mRNA resulted in downregulation of IL-6 production. We conclude that survivin determines the erosive course of RA, whereas survivin antibodies lead to a less aggressive course of the disease. These findings together with decreased survivin levels upon disease-modifying anti-rheumatic drug treatment, and the downregulation of inflammatory response using survivin anti-sense oligonucleotides, suggest that extracellular survivin expression mediates the erosive course of joint disease whereas autoimmune responses to the same molecule, manifested as survivin targeting antibodies, mediate protection.
Analysis of the role of the PAC1 receptor in neutrophil recruitment, acute-phase response, and nitric oxide production in septic shock
Authors: Martínez Carmen , Juarranz Yasmina , Abad Catalina , Arranz Alicia , Miguel Begoña G , Rosignoli Florencia , Leceta Javier , Gomariz Rosa P
Published: January 2005

Infections caused by Gram-negative bacteria constitute one of the major causes of septic shock, which results from the inability of the immune system to limit bacterial spread during the ongoing infection. In the last decade, it has been demonstrated that vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activing polypeptide (PACAP) are two endogenous immunopeptides, which together with three G protein-coupled receptors (VPAC1, VPAC2, and PAC1) exert a significant, therapeutic effect attenuating the deleterious consequences of septic shock by balancing pro- and anti-inflammatory factors. We have recently shown PAC1 receptor involvement in vivo as an anti-inflammatory receptor, at least in part, by attenuating lipopolysaccharide-induced production of proinflammatory interleukin-6. The present study deepens in the protective role of PAC1 receptor in septic shock, elucidating its involvement in the modulation of neutrophil recruitment and in the expression of different molecular sensors such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, fibrinogen, serum amyloid A, and nitric oxide as important, systemic players of the development of septic shock. Our results, using a mice deficient in PAC1 and a PAC1 antagonist, show that VIP and PACAP as well as the PAC1 receptor are involved in neutrophil recruitment in different target organs, in adhesion molecules expression, and in coagulation-related molecule fibrinogen synthesis. Thus, this study provides some important insights with respect to the involvement of PAC1 into the complexities of sepsis and represents an advantage for the design of more specific drugs complementing standard intensive care therapy in severe sepsis, confirming VIP and PACAP as candidates for multitarget therapy of septic shock.
Thymocyte stimulation by anti-TCR-β, but not by anti-TCR-α, leads to induction of developmental transcription program
Authors: Niederberger Nathalie , Buehler Lukas K , Ampudia Jeanette , Gascoigne Nicholas R J
Published: January 2005

Anti-T cell receptor (aTCR) antibody (Ab) stimulation of T cells results in TCR down-modulation and T cell activation. Differences in the effect of anti-α-chain and β-chain Ab have been reported on thymocytes. Anti-β-chain Ab but not anti-α-chain reagents cause long-term TCR down-modulation. However, both types of Ab result in TCR cross-linking and activate early steps in signal transduction. In this study, we show that TCR iternalization and calcium flux, hallmarks of T cell activation, are similar with aVα and aVβ treatment. Therefore, we have compared the gene expression profiles of preselection thymocytes stimulated with these reagents. We find that aVα treatment does not cause any significant change in gene expression compared with control culture conditions. In contrast, aVβ stimulation results in numerous changes in gene expression. The alterations of expression of genes known to be expressed in thymocytes are similar to changes caused by positive thymic selection, suggesting that the expression of some of the genes without known roles in thymocyte development and of novel genes whose expression is found to be altered may also be involved in this process.
Differential Estrogen Receptor Expression in Autoimmune Myasthenia Gravis
Authors: Nancy Patrice , Berrih-Aknin Sonia
Published: January 2005

Myasthenia gravis (MG) is an autoimmune disease associated with thymic hyperplasia and is much more prevalent in women than men. In this study we investigated potential changes in estrogen receptor (ER) expression in thymic hyperplasia. We first quantified by real-time PCR the relative expression of ERα and ERβ in normal thymus and found that the ERβ to ERα ratio was inverted in thymocytes (8.6 ± 1.2), compared with thymic epithelial cells (0.18 ± 0.05). The ER transcript number gradually decreased in thymic epithelial cells during culture, indicating that the thymic environment influences ER expression. CD4+ helper T cells expressed higher level of ERs, compared with CD8+ cells, as assessed by flow cytometry in thymocytes and peripheral blood mononuclear cells. In MG patients, we found an increased expression of ERα on thymocytes and both ERs on T cells from peripheral blood mononuclear cells, indicating that the signals provided by thymic and peripheral microenvironments are distinct. Finally, activation of normal thymocytes by proinflammatory cytokines induced increased expression of ERs especially in the CD4+ subset, suggesting that an excess of proinflammatory cytokines could explain the increase of ERs expression on MG lymphocytes. The dysregulation of ER expression in MG lymphocytes could affect the maintenance of the homeostatic conditions and might influence the progression of the autoimmune response.