Controlling the troll.
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Biomedical subjects
Publications and source records attributed to Julie Stoner.
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BACKGROUND: Cytomegalovirus (CMV), the most common opportunistic viral infection in solid organ transplant recipients, is associated with substantial morbidity and mortality. PURPOSE: To assess the efficacy of universal prophylaxis and preemptive approaches in preventing CMV organ disease and other complications in solid organ transplant recipients. DATA SOURCES: Using no language restrictions, the authors searched the following databases from their inception through May 2005: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Evidence-Based Medicine. The authors also reviewed abstracts from scientific meetings and contacted experts and pharmaceutical companies. STUDY SELECTION: Randomized, controlled trials that evaluated antiviral strategies for preventing CMV and associated complications in solid organ transplant recipients were selected. DATA EXTRACTION: Two reviewers independently extracted and assessed the data. DATA SYNTHESIS: The authors found 17 trials involving 1980 patients. Compared with placebo or no therapy, both universal prophylaxis (odds ratio [OR], 0.20 [95% CI, 0.13 to 0.31]) and preemptive strategies (OR, 0.28 [CI, 0.11 to 0.69]) reduced CMV organ disease. However, only universal prophylaxis seemingly reduced CMV organ disease in subgroups of patients at highest risk (donors with positive CMV serostatus and recipients with negative CMV serostatus and induction with antibodies). Both strategies reduced the rate of allograft rejection. Only universal prophylaxis statistically significantly reduced bacterial and fungal infections (OR, 0.49 [CI, 0.36 to 0.67]) and death (OR, 0.62 [CI, 0.40 to 0.96]). Both acyclovir and ganciclovir statistically significantly prevented CMV organ disease in the universal prophylaxis trials. LIMITATIONS: Studies were of modest size, and few studies assessed all outcomes. Studies did not always provide data that discriminated between CMV organ disease and CMV syndrome or data about the timing of CMV organ disease. CONCLUSIONS: Universal prophylaxis and preemptive strategies are beneficial in preventing CMV organ disease in solid organ transplant recipients. Both strategies are associated with a reduction in allograft rejection, but current data suggest that only universal prophylaxis reduces bacterial and fungal infections and death. Acyclovir and ganciclovir are both effective for universal prophylaxis.
Very few studies have thoroughly examined the discrepancies between the financial information in the Medicare Cost Report (MCR) and that in the audited hospital financial statement (FS). Furthermore, this type of study has never been conducted for rural hospitals. In this policy brief, we present the findings from our study, which used statistical methods to examine the agreement between the MCR and the FS of a series of financial measures in rural hospitals. The results are expected to inform policy makers of the limitation inherent in using MCR data as the single source of data to examine the financial performance of rural hospitals.
Laryngopharyngeal reflux (LPR) is becoming recognized as a clinical entity with a variety of presentations distinct from those of gastroesophreflux disease (GERD). However, much uncertainty remains as to what is considered pathologic versus physiologic reflux. The aim of the study was to determine the normal range of pharyngeal reflux (PR) occurring in healthy adults based on pH-monitoring parameters utilized in the DeMeester scoring system for GERD. We have reviewed the current pool of prospective literature examining ambulatory dual-channel pH-monitoring study data derived from hypopharyngeal proximal probes in normal adults. From our review we have identified trends in several monitoring parameters based on the DeMeester scoring system for GERD. Our discussion recognizes and accepts the limitations imposed by small sample sizes and the number of healthy individuals that would be required to determine the general adult physiologic range of PR. We also explore the possible need for separate normal PR reference intervals based on age or gender disparities. Additional discussion and the summary address future directions for LPR research notably, (1) identification of the most appropriate research paradigm for LPR (i.e., pH 4 vs. 5), (2) establishing reproducibility for the appropriate LPR research paradigm, and (3) complementary modalities to ambulatory dual-channel pH monitoring for the study of acid and nonacid bolus movement within the esophagus
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The human bronchial epithelial cell is one of the first cell types to be exposed to the irritants and toxins present in inhaled cigarette smoke. The ability of the bronchial epithelium to modulate inflammatory and immune events in response to cigarette smoke is important in the pathogenesis of smoke-induced airway injury. We have shown that cigarette smoke extract and the complement anaphylatoxin C5a both independently induce increased expression of intercellular adhesion molecule (ICAM)-1 on airway epithelial monolayers compared with unstimulated cells in vitro. This enhanced ICAM-1 expression is associated with a greater capacity of the airway epithelial cells to bind mononuclear cells, a process that appears to require the proinflammatory cytokine tumor necrosis factor-alpha and protein kinase C intracellular signaling. Exposure of epithelial monolayers to the combination of cigarette smoke followed by C5a results in an additive response for ICAM-1 expression and mononuclear cell adhesion compared with smoke or C5a challenge alone. Inhibiting C5a receptor expression can attenuate these responses. These findings suggest that smoke exposure in some way enhances the functional responsiveness of the C5a receptor expressed on these airway epithelial cells for subsequent C5a-mediated increases in ICAM-1 expression and mononuclear cell adhesion. Our results may help explain the initiation and propagation of inflammatory events in vivo induced by chronic airway exposure to cigarette smoke.
TGF-beta1 is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGF-beta isoforms affect TGF-beta production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFLF) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TGF-beta1, -beta2, or -beta3. Post-culture media were collected for ELISA assays of TGF-beta1, -beta2, and -beta3. TGF-beta mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TFG-beta2 and -beta3 stimulated TGF-beta1 production significantly (p < 0.01 relative to control). TGF-beta1 stimulated TGF-beta2 production (p < 0.01 relative to control). TGF-beta3 was undetectable. Glucocorticoids significantly inhibited TGF-beta1 and TGF-beta2 production and reduced expression of the up-regulated TGF-beta1 and TGF-beta2 mRNA induced by exogenous TGF-beta1, -beta2, or -beta3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF-beta-stimulated cells, it was reduced by glucocorticoids. Thus, TGF-beta isoforms may stimulate production of various TGF-beta isoforms in the lung. Glucocorticoids then may block TGF-beta production by modulating mRNA levels and c-Jun.
PURPOSE: The purpose of this study was to determine whether a correlation exists between passing the United States Medical Licensing Examination (USMLE) Step 1 (USMLE) on the first attempt and performance on National Board Dental Examination Part I (NBDE). MATERIALS AND METHODS: Questionnaires were sent to program directors of 52 dual-degree oral and maxillofacial surgery programs. The information requested concerned residents of each program from 1990 to 2000 and included NBDE scores and number of attempts each resident took to pass the USMLE Step 1. Also included was the number of years of medical school each program required, as well as time given to USMLE Step 1 study preparation. The data were analyzed to determine if a relationship exists between NBDE Part I score and pass rate on the USMLE Step 1 on the first attempt. Data presented are the mean +/- SD. RESULTS: Questionnaires were received from 26 of 52 (50%) dual-degree oral and maxillofacial surgery programs regarding 426 residents. The overall average of NBDE Part 1 was 92.55 +/- 3.62 (range, 83 to 99). The average NBDE Part I score for those candidates who passed the USMLE Step 1 on the first attempt was 93.75 +/- 3.02, and for those who did not pass the USMLE Step 1 on the first attempt, it was 89.12 +/- 2.93. The average NBDE Part I score is significantly higher for those subjects who passed the USMLE Step 1 on the first attempt (P <.001). A candidate with an NBDE Part I score of 95 to 99 is 75 times more likely to pass the USMLE Step 1 on the first attempt than is a candidate with a score of less than 90. A marginal association was found with study preparation time and amount of medical school completed during residency. CONCLUSIONS: A significant correlation exists between NBDE Part I score and pass rate on the USMLE Step 1 examination.
OBJECTIVE: To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). METHODS: RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. RESULTS: Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. CONCLUSION: The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ.
TGF-beta is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGB-beta isoforms affect TGF-beta production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFL-1) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TFG-beta1, -beta2, and -beta3. TGF-beta mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TGF-beta2 and -beta3 stimulated TGF-beta1 production significantly (p < 0.01 relative to control). TGF-beta1 stimulated TGF-beta2 production (p < 0.01 relative to control). TGF-beta3 was undetectable. Glucocorticoids significantly inhibited TGF-beta1 and -beta2 production and reduced expression of the upregulated TGF-beta1 and -beta2 mRNA induced by exogenous TGF-beta1, -beta2 or -beta3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF-beta-stimulated cells, it was reduced by glucocorticoids. Thus, TGF-beta isoforms may stimulate production of various TGF-beta isoforms in the lung. Glucocorticoids then may block TGF-beta production by modulating mRNA levels and c-Jun.