bluuebunny/crossref_metadata_2025 huggingface dataset:
Cause Celebre: Georgetown University Hospital’s Journey to Magnet
Authors: Johnson Joyce , Billingsley Molly , May Cheryl , Costa Linda L. , Hanson Kate
Published: October 2004

Designation as a magnet organization by the American Nurses Credentialing Center is a coveted distinction for health care organizations. These organizations experience fewer problems with nurse recruitment and retention because they have been found to be good places to practice professional nursing. Better patient outcomes have also been documented in these organizations. In this article, the authors recount their 3-year experience leading an organization successfully to become the first magnet organization in the nation’s capitol. The magnet application and review process is linked to the core principles of organization development. The authors conclude with policy recommendations for other organizations that are just beginning their journey to achieving magnet status and with reflections on leadership and the value created by participating in the magnet program.
Operationalizing Professional Values Through PAC Donations
Authors: Kent Rebekah L. , Liaschenko Joan
Published: October 2004

This article describes how campaign contributions reflect the organization values of nursing and medicine. The authors analyzed the contributions made by the American Nursing Association’s political action committee (PAC), the ANA-PAC, and the American Medical Association’s PAC, AmPAC, to candidates for the U.S. House and Senate from 1989 to 2002. The authors compared this information with the official positions of both groups on health care reform, as put forth in their official publications on the subject. The authors found that ANAPAC consistently contributed to the campaigns of Democrats, who are more likely to support the same reform policies as nurses. In addition, it was discovered that AmPAC supported Republicans to a higher degree, although their contribution strategy was more mixed. These contributions reflect each organization’s values regarding health care reform.
The Art and Science of Policy Choice
Authors: Jennings Carole P.
Published: October 2004

This article focuses on the art and science of policy choice reflected through a careful process of policy analysis. Recent policy events requiring analysis are discussed, and models for analysis are presented as a guide for the beginning policy analyst. In addition, philosophies of governance are presented relative to policy agenda setting.
Diabetes Mellitus: Toward a Federal Policy
Authors: Rocchiccioli Judith T. , O’Donoghue Cynthia R.
Published: October 2004

Diabetes is a serious global problem. Recent projections suggest that at least 194 million people suffer from diabetes worldwide, and the World Health Organization (2004) suggests that this number will increase to 333 million by 2025. Currently diabetes affects 15 million people (about 8% of the population) in the United States. In addition, an estimated 12 million people in the United States have diabetes and are undiagnosed. The costs of this multifaceted illness cannot be quantified, but financial analysts suggest that they are staggering. This article supports the development of a federal policy on diabetes mellitus in an effort to control, provide fair and equitable access to care, and improve culturally appropriate outreach strategies.
Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-β2 glycoprotein I antibodies
Authors: Zhang Jianwei , McCrae Keith R.
Published: October 2004

Patients with antiphospholipid antibodies (APLAs) are at increased risk for arterial and venous thrombosis. Many APLAs associated with these events react with β2 glycoprotein I (β2GPI), and endothelial cell reactive antibodies that activate endothelial cells in a β2GPI-dependent manner occur commonly in these patients. We previously reported that β2GPI binds with high affinity to annexin A2 on the endothelial surface, though the relevance of this interaction to APLA/anti-β2GPI antibody–induced endothelial activation has not been determined. In this report, we confirm that anti-β2GPI antibodies activate endothelial cells in the presence of β2GPI, and demonstrate that anti–annexin A2 antibodies directly cause endothelial cell activation of a similar magnitude and with a similar time course. Moreover, bivalent anti–annexin A2 F(ab′)2 fragments also caused endothelial cell activation, whereas monomeric Fab fragments not only did not cause activation, but blocked activation induced by anti–annexin A2 antibodies and F(ab′)2 fragments, as well as that caused by anti-β2GPI antibodies in the presence of β2GPI. These observations suggest a novel pathway for endothelial activation induced by APLA/anti-β2GPI antibodies that is initiated by cross-linking or clustering of annexin A2 on the endothelial surface.
Differential regulation of virus-specific T-cell effector functions following activation by peptide or innate cytokines
Authors: Beadling Carol , Slifka Mark K.
Published: October 2004

Robust CD8+ T-cell activation is vital for the recovery from many viral infections and is orchestrated via the integration of signals delivered through surface molecules, including the T-cell antigen receptors (TcRs) and cytokine receptors. Little is known about how virus-specific T cells interpret sequential or combined stimulation through these receptors, which must undoubtedly occur in vivo during antiviral immune responses. When measured in real time, peptide antigen and the cytokines, interleukin 12 (IL-12) and IL-18, independently regulate the on/off kinetics of protective (interferon γ, tumor necrosis factor α) and immunomodulatory (IL-2, CD40L) cytokine production by activated T cells and memory T cells. The remarkable differences in effector functions elicited by innate or adaptive signals (IL-12/ IL-18 or peptide, respectively) illustrate the complex and stringent regulation of cytokine expression by CD8+ T cells. Together, these results indicate how antiviral T cells incorporate multiple signals from their local microenvironment and tailor their cytokine responses accordingly.
RNA integrity as a quality indicator during the first steps of RNP purifications : A comparison of yeast lysis methods
Authors: López de Heredia Miguel , Jansen Ralf-Peter
Published: October 2004

Background

The completion of several genome-sequencing projects has increased our need to assign functions to newly identified genes. The presence of a specific protein domain has been used as the determinant for suggesting a function for these new genes. In the case of proteins that are predicted to interact with mRNA, most RNAs bound by these proteins are still unknown. In yeast, several protocols for the identification of protein-protein interactions in high-throughput analyses have been developed during the last years leading to an increased understanding of cellular proteomics. If any of these protocols or similar approaches shall be used for the identification of mRNA-protein complexes, the integrity of mRNA is a critical factor.

Results

We compared the effect of different lysis protocols on RNA integrity. We report dramatic differences in RNA stability depending on the method used for yeast cell lysis. Glass bead milling and French Press lead to degraded mRNAs even in the presence of RNase inhibitors. Thus, they are not suitable to purify intact mRNP complexes or to identify specific mRNAs bound to proteins.

Conclusion

We suggest a novel protocol, grinding deep-frozen cells, for the preparation of protein extracts that contain intact RNAs, as lysis method for the purification of mRNA-protein complexes from yeast cells.
A comprehensive comparison of comparative RNA structure prediction approaches
Authors: Gardner Paul P , Giegerich Robert
Published: October 2004

Background

An increasing number of researchers have released novel RNA structure analysis and prediction algorithms for comparative approaches to structure prediction. Yet, independent benchmarking of these algorithms is rarely performed as is now common practice for protein-folding, gene-finding and multiple-sequence-alignment algorithms.

Results

Here we evaluate a number of RNA folding algorithms using reliable RNA data-sets and compare their relative performance.

Conclusions

We conclude that comparative data can enhance structure prediction but structure-prediction-algorithms vary widely in terms of both sensitivity and selectivity across different lengths and homologies. Furthermore, we outline some directions for future research.
Is autoinducer-2 a universal signal for interspecies communication: a comparative genomic and phylogenetic analysis of the synthesis and signal transduction pathways
Authors: Sun Jibin , Daniel Rolf , Wagner-Döbler Irene , Zeng An-Ping
Published: October 2004

Background

Quorum sensing is a process of bacterial cell-to-cell communication involving the production and detection of extracellular signaling molecules called autoinducers. Recently, it has been proposed that autoinducer-2 (AI-2), a furanosyl borate diester derived from the recycling of S-adenosyl-homocysteine (SAH) to homocysteine, serves as a universal signal for interspecies communication.

Results

In this study, 138 completed genomes were examined for the genes involved in the synthesis and detection of AI-2. Except for some symbionts and parasites, all organisms have a pathway to recycle SAH, either using a two-step enzymatic conversion by the Pfs and LuxS enzymes or a one-step conversion using SAH-hydrolase (SahH). 51 organisms including most Gamma-, Beta-, and Epsilonproteobacteria, and Firmicutes possess the Pfs-LuxS pathway, while Archaea, Eukarya, Alphaproteobacteria, Actinobacteria and Cyanobacteria prefer the SahH pathway. In all 138 organisms, only the three Vibrio strains had strong, bidirectional matches to the periplasmic AI-2 binding protein LuxP and the central signal relay protein LuxU. The initial two-component sensor kinase protein LuxQ, and the terminal response regulator luxO are found in most Proteobacteria, as well as in some Firmicutes, often in several copies.

Conclusions

The genomic analysis indicates that the LuxS enzyme required for AI-2 synthesis is widespread in bacteria, while the periplasmic binding protein LuxP is only present in Vibrio strains. Thus, other organisms may either use components different from the AI-2 signal transduction system of Vibrio strains to sense the signal of AI-2, or they do not have such a quorum sensing system at all.
On modeling locus heterogeneity using mixture distributions
Authors: Lin Shili , Biswas Swati
Published: October 2004

Background

Locus heterogeneity poses a major difficulty in mapping genes that influence complex genetic traits. A widely used approach to deal with this problem involves modeling linkage data in terms of finite mixture distributions. In its simplest setup, also known as the admixture approach, a single parameter is used to model the probability that the disease-causing gene of a family is linked to a reference marker. This parameter is usually interpreted as the overall proportion of linked families.

Results

In this article, we address two issues regarding the admixture approach. First, we tackle the question of whether the single parameter of linked proportion is well defined in general. By formulating the likelihood under a classification scheme based on distributions, we show that such a parameter is meaningful only when a certain well-characterized condition is met. Second, we study a condition given in the literature for validating the admixture approach. A counter example is constructed to illustrate that the condition does not necessarily lead to valid estimates.

Conclusions

Estimators from the admixture approach may be inconsistent. This holds even if a condition given in the literature to validate the approach is satisfied.
Diagnostic polymorphisms in the mitochondrial cytochrome b gene allow discrimination between cattle, sheep, goat, roe buck and deer by PCR-RFLP
Authors: Pfeiffer Ina , Burger Joachim , Brenig Bertram
Published: October 2004

Background

As an alternative to direct DNA sequencing of PCR products, random PCR-RFLP is an efficient technique to discriminate between species. The PCR-RFLP-method is an inexpensive tool in forensic science, even if the template is degraded or contains only traces of DNA from various species.

Results

Interspecies-specific DNA sequence polymorphisms in the mitochondrial cytochrome b gene were analyzed using PCR-RFLP technology to determine the source (i.e., species) of blood traces obtained from a leaf.

Conclusions

The method presented can be used for the discrimination of cattle (Bos taurus), sheep (Ovis aries), goat (Capra hircus), roe buck (Capreolus capreolus) and red deer (Cervus elaphus).
Effect of straining on diaphragmatic crura with identification of the straining-crural reflex. The "reflex theory" in gastroesophageal competence
Authors: Shafik Ahmed , Shafik Ali A , El Sibai Olfat , Mostafa Randa M
Published: October 2004

Background

The role of the crural diaphragm during increased intra-abdominal pressure is not exactly known. We investigated the hypothesis that the crural diaphragm undergoes reflex phasic contraction on elevation of the intra-abdominal pressure with a resulting increase of the lower esophageal pressure and prevention of gastro-esophageal reflux.

Methods

The esophageal pressure and crural diaphragm electromyographic responses to straining were recorded in 16 subjects (10 men, 6 women, age 36.6 ± 11.2 SD years) during abdominal hernia repair. The electromyogram of crural diaphragm was recorded by needle electrode inserted into the crural diaphragm, and the lower esophageal pressure by a saline-perfused catheter. The study was repeated after crural anesthetization and after crural infiltration with saline.

Results

The crural diaphragm exhibited resting electromyographic activity which showed a significant increase on sudden (coughing, p < 0.001) or slow sustained (p < 0.01) straining with a mean latency of 29.6 ± 4.7 and 31.4 ± 4.5 ms, respectively. Straining led to elevation of the lower esophageal pressure which was coupled with the increased electromyographic activity of the crural diaphragm. The crural response to straining did not occur during crural diaphragm anesthetization, while was not affected by saline infiltration. The lower esophageal pressure declined on crural diaphragm anesthetization.

Conclusions

Straining effected an increase of the electromyographic activity of the crural diaphragm and of the lower esophageal pressure. This effect is suggested to be reflex in nature and to be mediated through the "straining-crural reflex". The crural diaphragm seems to play a role in the lower esophageal competence mechanism. Further studies are required to assess the clinical significance of the current results in gastro-esophageal reflux disease and hiatus hernia.
Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ISRCTN84121379]
Authors: van de Vusse Anton C , Stomp-van den Berg Suzanne GM , Kessels Alfons HF , Weber Wim EJ
Published: October 2004

Background

Complex Regional Pain Syndrome type one (CRPS I) or formerly Reflex Sympathetic Dystrophy (RSD) is a disabling syndrome, in which a painful limb is accompanied by varying symptoms. Neuropathic pain is a prominent feature of CRPS I, and is often refractory to treatment. Since gabapentin is an anticonvulsant with a proven analgesic effect in various neuropathic pain syndromes, we sought to study the efficacy of the anticonvulsant gabapentin as treatment for pain in patients with CRPS I.

Methods

We did a randomized double blind placebo controlled crossover study with two three-weeks treatment periods with gabapentin and placebo separated by a two-weeks washout period. Patients started at random with gabapentin or placebo, which was administered in identical capsules three times daily. We included 58 patients with CRPS type 1.

Results

Patients reported significant pain relief in favor of gabapentin in the first period. Therapy effect in the second period was less; finally resulting in no significant effect combining results of both periods. The CRPS patients had sensory deficits at baseline. We found that this sensory deficit was significantly reversed in gabapentin users in comparison to placebo users.

Conclusions

Gabapentin had a mild effect on pain in CRPS I. It significantly reduced the sensory deficit in the affected limb. A subpopulation of CRPS patients may benefit from gabapentin.
Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome
Authors: Okada Tomohisa , Tanaka Masaaki , Kuratsune Hirohiko , Watanabe Yasuyoshi , Sadato Norihiro
Published: October 2004

Background

Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue.

Methods

Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects.

Results

We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects.

Conclusion

These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue.
Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)
Authors: Pereira José Rodrigues , Martins Sandro J , Nikaedo Sueli M , Ikari Flora K
Published: October 2004

Background

Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients.

Methods

In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years), younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2), and older patients were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2). We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy.

Results

Analysis was by intention to treat. Main toxicities (grade 3–4) was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP) and overall survival (OS) were 27.0 (95% CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively.

Conclusion

Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions.
Cytotoxicity of psammaplin A from a two-sponge association may correlate with the inhibition of DNA replication
Authors: Jiang Yahong , Ahn Eun-Young , Ryu Seung Hee , Kim Dong-Kyoo , Park Jang-Su , Yoon Hyun Joo , You Song , Lee Burm-Jong , Lee Dong Seok , Jung Jee H
Published: October 2004

Background

SV40 DNA replication system is a very useful tool to understand the mechanism of replication, which is a tightly regulated process. Many environmental and cellular factors can induce cell cycle arrest or apoptosis by inhibiting DNA replication. In the course of our search for bioactive metabolites from the marine sponges, psammaplin A was found to have some anticancer properties, the possible mechanism of which was studied.

Methods

Cell viability was determined by Cell Counting Kit-8 (CCK-8) to count living RAW264.7 cells by combining 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-8) and 1-methoxy-phenazine methosulfate (1-methoxy-PMS). The effect of psammaplin A on DNA replication was carried out in SV40 DNA replication system in vitro. The activities of topoisomerase I and polymerase α-primase were measured by the relaxation of superhelical plasmid DNA and the incorporation of [3H]dTTP to the template respectively. The ssDNA binding activity of RPA was assessed by Gel Mobility Shift Assay (GMSA).

Results

We have found that psammaplin A delivers significant cytotoxic activity against the RAW264.7 cell line. It was also found that psammaplin A could substantially inhibit SV40 DNA replication in vitro, in which polymerase α-primase is one of its main targets.

Conclusion

Taken together, we suggest that psammaplin A-induced cytotoxicity may correlate with its inhibition on DNA replication. Psammaplin A has the potential to be developed as an anticancer drug.
Morphine for elective endotracheal intubation in neonates: a randomized trial [ISRCTN43546373]
Authors: Lemyre Brigitte , Doucette Joanne , Kalyn Angela , Gray Shari , Marrin Michael L
Published: October 2004

Background

Elective endotracheal intubations are still commonly performed without premedication in many institutions. The hypothesis tested in this study was that morphine given prior to elective intubations in neonates would decrease fluctuations in vital signs, shorten the duration of intubation and reduce the number of attempts.

Methods

From December 1999 to September 2000, infants of all gestations admitted to a level III neonatal intensive care unit and requiring an elective endotracheal intubation were randomly assigned to receive morphine 0.2 mg/kg IV or placebo 5 minutes before intubation. Duration of severe hypoxemia (HR< 90/min and Sp02<85%), duration of procedure, duration of hypoxemia (Sp02<85%), number of attempts and change in mean blood pressure were compared between groups.

Results

34 infants (median 989 g and 28 weeks gestation) were included. The duration of severe hypoxemia was similar between groups. Duration of procedure, duration of hypoxemia, number of attempts and increases in mean blood pressure were also similar between groups. 94% of infants experienced bradycardia during the procedure.

Conclusion

We failed to demonstrate the effectiveness of morphine in reducing the physiological instability or time needed to perform elective intubations. Alternatives, perhaps with more rapid onset of action, should be considered.
The impact of employee level and work stress on mental health and GP service use: an analysis of a sample of Australian government employees
Authors: Parslow Ruth A , Jorm Anthony F , Christensen Helen , Broom Dorothy H , Strazdins Lyndall , D' Souza Rennie M
Published: October 2004

Background

This study sought to identify the extent to which employee level and work stressors were associated with mental health problems experienced by Australian government employees, and with their use of primary care services.

Methods

806 government employees aged between 40 and 44 years were surveyed as part of an epidemiological study conducted in Australia. Data collected from participants included sociodemographic attributes, physical health, psychological measures and work stressors relating to job control, job demands, job security and skills discretion at work. For 88% of these participants, information on visits made to general practitioners (GPs) for the six months before and after their survey interview was obtained from health insurance records.

Results

When work stress and personal factors were taken into account, men at more junior levels reported better mental health, more positive affect and used fewer GP services. Women at middle-management levels obtained less GP care than their more senior counterparts. Both men and women who reported higher levels of work stress were found to have poorer mental health and well-being. The impact of such stressors on GP service use, however, differed for men and women.

Conclusion

Measures of work stress and not employee level affect the mental health and well-being of government employees. For governments with responsibility for funding health care services, reducing work stress experienced by their own employees offers potential benefits by improving the health of their workforce and reducing outlays for such services.
Is nebulized saline a placebo in COPD?
Authors: Khan Shahina Y , O'Driscoll B Ronan
Published: October 2004

Background

Many trials of nebulized therapy have used nebulized saline as a "placebo". However, nebulized isotonic saline is sometimes used to assist sputum expectoration and relieve breathlessness in COPD patients. We designed this study to establish if nebulized saline had a placebo effect or a clinical effect.

Methods

40 patients were studied following hospital admission for exacerbated COPD (mean FEV1 30% predicted). Patients were randomised to single-blind administration of either 4 mls of nebulized isotonic saline using an efficient nebulizer (active group n = 20) or an inefficient nebulizer (placebo group n = 20). Spirometry and subjective breathlessness scores (Modified Likert Scale) were measured before nebulized treatment and 10 minutes after treatment.

Results

There was no significant change in FEV1 after active or placebo nebulized saline treatment. Patients reported a 4% improvement in mean breathlessness score following placebo (Wilcoxon test; p = 0.37) compared with 23% improvement following active nebulized saline (p = 0.0001). 65% of patients given active nebulized saline but only 5% of the placebo group reported that mucus expectoration was easier after the treatment.

Conclusions

This study lends support to the current use of nebulized saline to relieve breathlessness (possibly by facilitating sputum clearance) in COPD patients. Lung function was not affected. Nebulized saline can therefore be used as a placebo in bronchodilator studies involving COPD patients but it cannot be used as a placebo in trials assessing symptom relief.
Electroesophagogram in gastroesophageal reflux disease with a new theory on the pathogenesis of its electric changes
Authors: Shafik Ahmed , El-Sibai Olfat , Shafik Ismail , Shafik Ali
Published: October 2004

Background

In view of the disturbed esophageal peristaltic activity and abnormal esophageal motility in gastroesophageal reflux disease, (GERD), we investigated the hypothesis that these changes result from a disordered myoelectric activity of the esophagus.

Methods

The electric activity of the esophagus (electroesophagogram, EEG) was studied in 27 patients with GERD (16 men, 11 women, mean age 42.6 ± 5.2 years) and 10 healthy volunteers as controls (6 men, 4 women, mean age 41.4 ± 4.9 years). According to the Feussner scoring system, 7 patients had a mild (score 1), 10 a moderate (score 2) and 10 a severe (score 3) stage of the disease. One electrode was applied to the upper third and a second to the lower third of the esophagus, and the electric activity was recorded. The test was repeated after the upper electrode had been moved to the mid-esophagus.

Results

The EEG of the healthy volunteers showed slow waves and exhibited the same frequency, amplitude and conduction velocity from the 2 electrodes of the individual subject, regardless of their location in the upper, middle or lower esophagus. Action potentials occurred randomly. In GERD patients, score 1 exhibited electric waves' variables similar to those of the healthy volunteers. In score 2, the waves recorded irregular rhythm and lower variables than the controls. Score 3 showed a "silent" EEG without waves.

Conclusion

The electric activity in GERD exhibited 3 different patterns depending on the stages of GERD. Score 1 exhibited a normal EEG which apparently denotes normal esophageal motility. Score 2 recorded irregular electric waves variables which are presumably indicative of decreased esophageal motility and reflux clearance. In score 3, a "silent" EEG was recorded with probably no acid clearance. It is postulated that the interstitial cells of Cajal which are the electric activity generators, are involved in the inflammatory process of GERD. Destruction of these cells appears to occur in grades that are in accordance with GERD scores. The EEG seems to have the potential to act as an investigative tool in the diagnosis of GERD stages.
Mapping medical careers: Questionnaire assessment of career preferences in medical school applicants and final-year students
Authors: Petrides KV , McManus IC
Published: October 2004

Background

The medical specialities chosen by doctors for their careers play an important part in the workforce planning of health-care services. However, there is little theoretical understanding of how different medical specialities are perceived or how choices are made, despite there being much work in general on this topic in occupational psychology, which is influenced by Holland's RIASEC (Realistic-Investigative-Artistic-Social-Enterprising-Conventional) typology of careers, and Gottfredson's model of circumscription and compromise. In this study, we use three large-scale cohorts of medical students to produce maps of medical careers.

Methods

Information on between 24 and 28 specialities was collected in three UK cohorts of medical students (1981, 1986 and 1991 entry), in applicants (1981 and 1986 cohorts, N = 1135 and 2032) or entrants (1991 cohort, N = 2973) and in final-year students (N = 330, 376, and 1437). Mapping used Individual Differences Scaling (INDSCAL) on sub-groups broken down by age and sex. The method was validated in a population sample using a full range of careers, and demonstrating that the RIASEC structure could be extracted.

Results

Medical specialities in each cohort, at application and in the final-year, were well represented by a two-dimensional space. The representations showed a close similarity to Holland's RIASEC typology, with the main orthogonal dimensions appearing similar to Prediger's derived orthogonal dimensions of 'Things-People' and 'Data-Ideas'.

Conclusions

There are close parallels between Holland's general typology of careers, and the structure we have found in medical careers. Medical specialities typical of Holland's six RIASEC categories are Surgery (Realistic), Hospital Medicine (Investigative), Psychiatry (Artistic), Public Health (Social), Administrative Medicine (Enterprising), and Laboratory Medicine (Conventional). The homology between medical careers and RIASEC may mean that the map can be used as the basis for understanding career choice, and for providing career counselling.
Emphysematous cystitis: An unusual disease of the Genito-Urinary system suspected on imaging
Authors: Bobba Ravi K , Arsura Edward L , Sarna Pawanjit S , Sawh Amar K
Published: October 2004

Emphysematous cystitis is a rare disease entity caused by gas fermenting bacterial and fungal pathogens. Clinical symptoms are nonspecific and diagnostic clues often arise from the unanticipated imaging findings. We report a case of 52-year-old male who presented with fever, dysuria and gross hematuria who was found to have emphysematous cystitis.
Extraabdominal fibromatosis in retroperitoneal space
Authors: Kikkawa Akira , Kido Akira , Kumai Tsukasa , Hoshida Toru
Published: October 2004

Background

Fibromatosis or desmoid tumor covers a broad spectrum of benign fibrous tissue proliferations. It is characterized by infiltrative growth and a tendency towards recurrence; however, unlike sarcoma, it never metastasizes.

Case presentation

We report on a case of extraabdominal fibromatosis originating from the retroperitoneal space in a 43-year-old woman. Seven years earlier she had undergone ureterolysis and ureteroureterostomy for ureteral obstruction. Computed tomography revealed a tumor between the iliocostalis and the psoas muscle. Histopathological evaluation revealed uniform proliferation of spindle cells, with a moderate amount of collagen fibers, suggesting extraabdominal fibromatosis (desmoid tumor). The tumor was surgically resected, and since then, the patient has remained asymptomatic without any restrictions of daily living activities and without any signs of tumor recurrence during the two-year follow-up.

Conclusions

Complete resection is the treatment of choice. Adjuvant therapy using non steroidal anti-inflammatory agents, tamoxifen, interferon, anti-neoplastic agents, and radiotherapy, either alone or in combination finds application for unresectable or recurrent cases.
Metabolic aspects of low carbohydrate diets and exercise
Authors: Peters Sandra J , LeBlanc Paul J
Published: October 2004

Following a low carbohydrate diet, there is a shift towards more fat and less carbohydrate oxidation to provide energy to skeletal muscle, both at rest and during exercise. This review summarizes recent work on human skeletal muscle carbohydrate and fat metabolic adaptations to a low carbohydrate diet, focusing mainly on pyruvate dehydrogenase and pyruvate dehydrogenase kinase, and how these changes relate to the capacity for carbohydrate oxidation during exercise.
17β-Estradiol-Dependent Activation of Signal Transducer and Activator of Transcription-1 in Human Fetal Osteoblasts Is Dependent on Src Kinase Activity
Authors: Kennedy Angela M. , Shogren Kristen L. , Zhang Minzhi , Turner Russell T. , Spelsberg Thomas C. , Maran Avudaiappan
Published: October 2004

Estrogen is essential for normal growth and remodeling of bone. Although the mechanism of estrogen action on bone cells has been widely investigated, the full spectrum of signal transduction pathways activated by estrogen is unknown. In this report, we investigate the effects of the gonadal hormone 17β-estradiol on the regulation of signal transducer and activator of transcription-1 (Stat1) protein in cultured human fetal osteoblast cells, devoid of the classical estrogen receptors (ERs). 17β-Estradiol (10 nm) led to rapid (within 15 min) activation of Stat1 protein as indicated by increases in tyrosine phosphorylation and DNA binding activity. Also, 17β-estradiol increased γ-activated sequence-dependent transcription in transient transfection assays, suggesting an increase in Stat protein-dependent transcription. Estrogen-dependent Stat1 activation was blocked in cells that transiently express dominant-negative Stat1 mutant protein. Activation of Stat1 by 17β-estradiol was not inhibited by ER antagonist ICI 182,780, providing further evidence that it is not dependent on classical ERs. 17β-Estradiol induced rapid (within 15 min) Stat1 phosphorylation and stimulated γactivated sequence-dependent transcription in ER-negative breast cancer cells, indicating that these results are not unique to bone cells. The rapid estrogenic effect involving the phosphorylation and activation of Stat1 was blocked in the presence of Src family kinase inhibitor PP2; activated Stat1 was associated with Src protein in estrogen-treated cells. These findings indicate the requirement for Src kinase pathways in estrogen-mediated Stat1 activation. Thus, the ER-independent activation of Stat1 in 17β-estradiol-treated osteoblast and breast cancer cells may partially mediate the actions of estrogen on target cells.
Pdx-1 Is Not Sufficient for Repression of Proglucagon Gene Transcription in Islet or Enteroendocrine Cells
Authors: Flock Grace , Cao Xiemin , Drucker Daniel J.
Published: October 2004

Pdx-1 plays a key role in the development of the pancreas and the control of islet gene transcription and has also been proposed as a dominant regulator of the α- vs. β-cell phenotype via extinction of proglucagon expression. To ascertain the relationship between Pdx-1 and proglucagon gene expression, we examined the effect of enhanced pdx-1 expression on proglucagon gene expression in murine islet αTC-1 and GLUTag enteroendocrine cells. Although adenoviral transduction increased the levels of pdx-1 mRNA transcripts and nuclear Pdx-1 protein, overexpression of pdx-1 did not repress endogenous proglucagon gene expression in αTC-1 or GLUTag cells or murine islets. Immunohistochemical analysis of cells transduced with Ad-pdx-1 demonstrated multiple individual islet or enteroendocrine cells exhibiting both nuclear Pdx-1 and cytoplasmic glucagon-like peptide-1 immunopositivity. The failure of pdx-1 to inhibit endogenous proglucagon gene expression was not attributable to defects in Pdx-1 nuclear translocation or DNA binding as demonstrated using Western blotting and EMSA analyses. Furthermore, Ad-pdx-1 transduction did not repress proglucagon promoter activity in αTC-1 or GLUTag cells. Taken together, these findings demonstrate that pdx-1 alone is not sufficient for specification of the hormonal phenotype or extinction of proglucagon gene expression in islet or enteroendocrine cells.
Type 2 Iodothyronine Selenodeiodinase Is Expressed throughout the Mouse Skeleton and in the MC3T3-E1 Mouse Osteoblastic Cell Line during Differentiation
Authors: Gouveia Cecilia H. A. , Christoffolete Marcelo A. , Zaitune Clarissa R. , Dora José Miguel , Harney John W. , Maia Ana Luiza , Bianco Antonio C.
Published: October 2004

Thyroid hormone affects multiple aspects of bone metabolism, but little is known about thyroid hormone deiodination in bone cells except that cultures of skeletal cells and bone organ express types 1 and 2 iodothyronine deiodinases (D1 and D2) mRNAs. In the present study, outer ring deiodination (ORD) activity was detected in bone extracts of multiple sites of the mouse skeleton, bone marrow, and the MC3T3-E1 osteoblastic cell line. In all tissues, ORD was detected using 125I-rT3 or 125I-T4 as substrates and was found to be 6-n-propylthiouracil insensitive, display a Michaelis constant (T4) of approximately 1 nm, increase about 3-fold in hypo- and virtually disappear in thyrotoxicosis. Extracts of calvaria had the lowest ORD activity, whereas tibial and femoral extracts had roughly three times as much. The absence of ORD activity in bone extracts from mice with targeted disruption of the Dio2 gene confirms the principal role of D2 in this tissue. In the MC3T3-E1 osteoblasts, D2 activity increased in a time-dependent manner after plating, and with the content of selenium in the media, reaching a maximum 5–7 d later as cells attained more than 90% confluence. In these cells D2 half-life is about 30–40 min, which is further accelerated by exposure to substrate and stabilized by the proteasome inhibitor, MG132. Treatment with vitamin D [1,25(OH)2VD]-induced D2 activity by 2- to 3-fold as early as 24 h, regardless of the level of cell confluence, but estradiol, PTH, forskolin, leptin, TNFα, TGFβ, and dexamethasone did not affect D2. Given the role of D2 in other cell types and processes, it is likely that bone ORD not only plays a role in bone development and adult bone T3 homeostasis but also contributes to extrathyroidal T3 production and maintenance of serum T3.
A System for Studying Epithelial-Stromal Interactions Reveals Distinct Inductive Abilities of Stromal Cells from Benign Prostatic Hyperplasia and Prostate Cancer
Authors: Barclay Wendy W. , Woodruff Ralph D. , Hall M. Craig , Cramer Scott D.
Published: October 2004

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes, it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone, benign prostatic hyperplasia (BPH-S), and cancer to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone or BPH-1 epithelial cells alone produced no visible grafts. Recombining stromal cells from normal peripheral zone with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized, and sharply demarcated grafts approximately 3–4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining stromal cells from cancer with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye-stained specimens is an efficient method to generate high-quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo, which mimics the natural history of these diseases.
Detection of Anti-SSA Antibodies by Indirect Immunofluorescence
Authors: Bossuyt Xavier , Frans Johan , Hendrickx Ann , Godefridis Godelieve , Westhovens René , Mariën Godelieve
Published: October 2004

Background: HEp-2 cells that overexpress the human 60-kDa SSA antigen have been used to improve sensitivity and specificity for the detection of anti-SSA antibodies by indirect immunofluorescence. We describe a survey on the detection of anti-SSA antibodies using a commercial substrate that overexpresses SSA.

Methods: The evaluation was done on 18 371 consecutive samples submitted to the laboratory for detection of anti-nuclear antibodies, from which 188 anti-SSA antibody-containing and clinically documented samples were obtained. The presence of anti-SSA antibodies produced a distinct bright speckled pattern with nucleolar staining in 10–20% of interphase cells. The identity of all anti-SSA antibodies was confirmed by dot-blot analysis.

Results:Samples containing anti-SSA antibodies were separated into three main groups: group I, distinctive SSA pattern and other nuclear staining (50%); group II, only the distinctive SSA pattern (29%); group III, nuclear staining but without the distinctive SSA pattern (21%). Anti-SSA antibodies with concurrent SSB antibodies were associated with group I, whereas anti-SSA antibodies with concurrent U1-RNP antibodies were associated with group III. Group I included mainly patients with Sjögren syndrome and systemic lupus erythematosus (SLE), whereas group III included patients with mixed connective tissue disease and SLE. Diseases not classically associated with the presence of anti-SSA antibodies were found in group II in >50% of the cases.

Conclusions: SSA-positive individuals were identified in a population selected on the basis of HEp-2000 positivity. Our study highlights diseases associated with anti-SSA antibodies and associations between the presence of the distinctive SSA pattern on HEp-2000 and some clinical conditions.
Serologic Assay Based on Gliadin-Related Nonapeptides as a Highly Sensitive and Specific Diagnostic Aid in Celiac Disease
Authors: Schwertz Elke , Kahlenberg Franka , Sack Ulrich , Richter Thomas , Stern Martin , Conrad Karsten , Zimmer Klaus-Peter , Mothes Thomas
Published: October 2004

Background: Celiac disease (CD) is induced by wheat gliadins and related cereal proteins. Anti-gliadin antibodies (AGAs) are present in the serum of CD patients, but these antibodies have lower diagnostic specificity and sensitivity than autoantibodies [anti-endomysium antibodies (AEmAs) and anti-tissue transglutaminase antibodies (AtTGAs)]. Recently, AGAs from CD patients were found to recognize deamidated gliadin peptides, probably formed by the action of tissue transglutaminase.

Methods: We synthesized several gliadin peptides and their glutamine-glutamic acid-substituted counterparts on cellulose membranes and tested their recognition by IgA in sera of 52 AEmA-positive CD patients and 76 AEmA-negative controls in a luminescence assay. For comparison, we assayed IgA concentrations of AGAs, AtTGAs, and AEmAs. For measurement of AtTGAs, we used the human recombinant antigen.

Results: We identified several nonapeptides that were detected with high specificity by IgA in CD patients. Diagnostic accuracy of the peptide antibody assay was highest when peptide PLQPEQPFP was used in combination with peptide PEQLPQFEE within one assay. AGAs were above the cutoff in 14 of the controls, but only 5 of the controls were positive for peptide antibodies. For comparison, 82% and 94% of samples were correctly classified by AGAs and the combination nonapeptide assay, respectively (P = 0.007), and the AtTGAs correctly classified 98%.

Conclusion: The peptide antibody assay has higher diagnostic accuracy than AGAs for distinguishing patients with CD from controls, and has diagnostic accuracy similar to that of AtTGAs.
Performance Characteristics of Six Third-Generation Assays for Thyroid-Stimulating Hormone
Authors: Rawlins Mindy L , Roberts William L
Published: October 2004

Background: Thyroid-stimulating hormone (TSH) is used to detect primary hypo- and hyperthyroidism. Current guidelines for TSH assays recommend a functional sensitivity of ≤0.02 mIU/L. The protocol for determining the functional sensitivity of TSH assays specifies analyses of serum samples with two reagent lots over a 6- to 8-week period.

Methods: We determined the functional sensitivities of the Access 2, ADVIA Centaur, ARCHITECT i2000, E170, IMMULITE 2000, and Vitros ECi automated methods, using seven serum pools and two reagent lots for each method.

Results: The observed functional sensitivities were as follows: Access 2, <0.020 mIU/L; ADVIA Centaur, 0.039 mIU/L; ARCHITECT i2000, <0.005 mIU/L; Elecsys E170, 0.011 mIU/L; IMMULITE 2000, 0.014 mIU/L; Vitros ECi, 0.004 mIU/L. However, there were large differences between some method means for the seven serum pools. For the pool with the lowest TSH concentration, mean results were as follows: Access 2, 0.0203 mIU/L; ADVIA Centaur, 0.0085 mIU/L; ARCHITECT i2000, 0.0049 mIU/L; E170, 0.0098 mIU/L; IMMULITE 2000, 0.0077 mIU/L; Vitros ECi, 0.0014 mIU/L. Method-comparison studies using samples with TSH concentrations >0.2 mIU/L also showed method differences. The ARCHITECT i2000 method was the most precise at low TSH concentrations.

Conclusions: TSH methods do not provide comparable results for serum pools with TSH concentrations <0.2 mIU/L or for patient results across the analytic measurement range. Further investigation into the cause of these differences and additional harmonization efforts are required.