bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration
Authors: Brigotti Maurizio , Tazzari Pier Luigi , Ravanelli Elisa , Carnicelli Domenica , Barbieri Stefania , Rocchi Laura , Arfilli Valentina , Scavia Gaia , Ricci Francesca , Bontadini Andrea , Alfieri Roberta R , Petronini Pier Giorgio , Pecoraro Carmine , Tozzi Alberto E , Caprioli Alfredo 
Published: April 2010

Abstract
Intoxicated endothelial cells release pro-inflammatory cytokines involved in renal damage; amount of cytokines inversely correlates with the amount of toxin carried by PMN.
The endothelial damage induced by Stx represents the main pathogenic event in the HUS associated with STEC infections in humans. Stx, released in the gut by bacteria, enter the bloodstream and are targeted to renal endothelia. The role of PMN as a toxin carrier has been the object of controversy. In this paper, we confirm the binding of Stx1 to PMN, also showing its degranulating effects on full-loaded leukocytes, and support the carrier role of PMN by using a two-chamber transmigration device, in which PMN, loaded in vitro with different amounts of Stx1, transmigrated through confluent monolayers of endothelial cells, mimicking the toxin-induced renal endothelial injury. Stx1 was transferred during PMN transmigration, impairing protein synthesis and triggering production of proinflammatory cytokines in endothelial cells. PMN, carrying low toxin amounts, induced the release of high levels of cytokines in viable endothelial cells, whereas cytokine production was blocked in cells challenged with PMN fully loaded with Stx as a result of an almost total impairment of translation and of the activation of the apoptotic program. In agreement with previous unexplained observations in animal models, the results obtained with our experimental setting suggest that a self-amplifying circle triggered by low doses of toxin may lead to the production of proinflammatory mediators of renal damage in HUS.
Circulating Estrogens in Endometrial Cancer Cases and Their Relationship with Tissular Expression of Key Estrogen Biosynthesis and Metabolic Pathways
Authors: Lépine Johanie , Audet-Walsh Etienne , Grégoire Jean , Têtu Bernard , Plante Marie , Ménard Vincent , Ayotte Pierre , Brisson Jacques , Caron Patrick , Villeneuve Lyne , Bélanger Alain , Guillemette Chantal 
Published: April 2010

AbstractBackground: Endometrial cancer is the most common gynecological malignancy. Estrogen exposure is strongly associated with endometrial cancer. Whereas this cancer occurs predominantly in postmenopausal women lacking estrogen production by ovaries, the conversion of adrenal androgen-estrogen precursors to estradiol (E2), estrone (E1), and its sulfate (E1-S) has been well documented in peripheral tissues.Experimental Design: We initially explored whether circulating levels of estrogens, measured by validated mass spectrometry assays, differ in women with endometrial cancer (n = 126) compared with healthy women (n = 110). We then evaluated by quantitative real-time PCR from purified RNA whether the expression profile of 19 estrogen-related synthesis and metabolic genes is modified in peritumoral normal endometrium (n = 36) compared with tumoral (n = 49) tissues.Results: In endometrial cancer cases, circulating levels of E1, E2, and E1-S were significantly higher compared with unaffected controls. In agreement with plasma levels, findings support an enhanced biosynthesis of E2 in tumors. The expression of E2 biosynthesis pathways [E1-S (sulfatase) → E1 (17β-hydroxysteroid dehydrogenase) → E2] was shown to predominate in peritumoral normal endometrium and was significantly increased in tumors. In addition, the inactivation pathways mediated by several uridine diphosphate-glucuronosyltransferases were also enhanced in endometrial tumors compared with peritumoral normal endometrium.Conclusion: We concluded that the higher levels of circulating estrogens in women with endometrial cancer are likely associated with an imbalance of multiple biotransformation pathways in endometrial tumor tissues.
Strategies of Power: Favorites and Women Household Clients at Louis Xiii's Court
Authors: Kettering Sharon 
Published: April 2010

Using household clients to acquire and keep royal favor was a widespread power strategy at the courts of early modern Europe. Trustworthy clients were placed in royal households to manipulate and report on their members and through them to influence the king. Favorites needed their help because their longevity in favor and thus in power depended on the king's continued goodwill. This article looks at the ways in which two minister-favorites of Louis XIII, Charles d'Albert, duc de Luynes, and his successor, Armand-Jean du Plessis, Cardinal de Richelieu, used their household clients to stay in power, demonstrating what has long been assumed but never proven. Specifically, it looks at fourteen noblewomen who were Luynes's clients, mostly in the young queen's household, and fifteen noblewomen who were Richelieu's clients in the queen mother's and the queen's households. Luynes used his clients and the tactic of rewards to influence members of the household and the king. In contrast, Richelieu used his clients and the tactic of punishment for the same purpose. Despite the difference in tactics both favorites succeeded in their goals.
L'utilisation d'une clientèle «domestique» dans le but de conquérir et conserver la faveur royale était courante dans les cours princières de l'Europe moderne. Des clients fidèles furent placés dans les maisons royales pour manipuler, mais aussi pour faire des rapports sur leurs membres et par leur intermédiaire influencer le roi. Les favoris avaient besoin d'eux, car la durée de leur faveur et pouvoir dépendait de la bienveillance du roi. Cet article examine comment deux ministres-favoris de Louis XIII, Charles d'Albert, duc de Luynes, et son successeur, Armand-Jean du Plessis, cardinal de Richelieu, employèrent leurs clients domestiques pour rester au pouvoir. Ainsi cet article démontre ce que les historiens ont longtemps pensé sans le prouver. Plus précisément, il analyse le cas de quatorze femmes nobles clientes du duc de Luynes qui servirent dans la maison de la jeune reine, Anne d'Autriche, et quinze femmes nobles clientes de Richelieu placées dans les maisons de la reine mère et de la reine régnante. Pour influencer certains membres de la maison du roi et le roi lui-même, de Luynes proposa à ses clientes des récompenses en cas de réussite. Richelieu faisait planer sur les siennes la menace de la punition. Malgré ces différences de tactique, les deux ministres finirent par atteindre leurs objectifs.
Adherence to a Fixed-Dose Combination of Rosiglitazone/Glimepiride in Subjects Switching from Monotherapy or Dual Therapy with a Thiazolidinedione and/or a Sulfonylurea
Authors: Thayer Sarah , Arondekar Bhakti , Harley Carolyn , Darkow Theodore E 
Published: April 2010

BACKGROUND: In 2005, a fixed-dose combination therapy (FDCT) of rosiglitazone maleate and glimepiride became available for treatment of type 2 diabetes mellitus. It is hypothesized that FDCTs increase adherence by decreasing the number of required tablets. OBJECTIVE: To assess changes in medication adherence and hemoglobin A1c (A1C) values in subjects switching from monotherapy with either a sulfonylurea or rosiglitazone or dual therapy with both to rosiglitazone/glimepiride FDCT. METHODS: This retrospective database analysis included subjects with 1 or more prescription fills for rosiglitazone, a sulfonylurea, or rosiglitazone/glimepiride FDCT during the identification period of January 1, 2006, to September 30, 2006. Subjects were grouped according to baseline and follow-up period treatment regimens: sulfonylurea or rosiglitazone monotherapy switched to sulfonylurea and rosiglitazone dual therapy (Mono/Dual), monotherapy to rosiglitazone/glimepiride FDCT (Mono/FDCT), sulfonylurea and rosiglitazone dual therapy in both periods (Dual/Dual), and dual therapy to rosiglitazone/glimepiride FDCT (Dual/FDCT). The medication possession ratio (MPR) was calculated as a measure of adherence. The change in A1C from the baseline period to the follow-up period was assessed for each cohort. RESULTS: The study included 16,490 subjects. From baseline to follow-up, MPR decreased for both the Mono/FDCT cohort and the Mono/Dual cohort, but the magnitude of this decrease was less for the Mono/FDCT cohort (−0.02 vs −0.10; p < 0.001). Mean MPR significantly improved for the Dual/FDCT cohort compared with the Dual/Dual cohort (+0.10 vs +0.05; p < 0.001). The mean absolute A1C reduction did not differ significantly between the Mono/FDCT cohort (−1.08%) and the Mono/Dual cohort (−0.77%). Compared with the Dual/Dual cohort, the Dual/FDCT cohort experienced a greater absolute reduction in A1C (−0.06% vs −0.51%; p = 0.004). The results remained statistically significant in the multivariate model. CONCLUSIONS: Switching to rosiglitazone/glimepiride FDCT, in comparison with switching to dual therapy, was associated with improvements in medication adherence and glycemic control.
Successful Experience Utilizing Dexrazoxane Treatment for an Anthracycline Extravasation
Authors: Tyson Abby Mercer , Gay Wendy E 
Published: April 2010

OBJECTIVE: To describe a successful case of dexrazoxane treatment after an extravasation of doxorubicin and share a creative solution for formulary cost management. CASE SUMMARY: A 42-year-old female diagnosed with breast cancer was receiving doxorubicin as adjuvant treatment. The patient recently underwent a right mastectomy for a 3-centimeter grade 3 invasive ductal carcinoma. Three of 20 lymph nodes were positive, and the patient was stage 2B at presentation, with an estrogen receptor/progesterone receptor-positive and HER-2/neu-negative tumor. At an outside hospital, the patient was receiving doxorubicin through an infusion port when extravasation was noted after approximately 15 mL had been infused. She was transferred to Riverside Methodist Hospital and dexrazoxane treatment was initiated within 6 hours after extravasation. She received a full 3-day course of dexrazoxane treatment without complication and was discharged home. Significant delays in chemotherapy administration were avoided, and the patient successfully completed her planned chemotherapy course. DISCUSSION: Dexrazoxane has the potential to minimize tissue damage and treatment delays after an anthracycline extravasation. Although dexrazoxane is commercially marketed for 2 separate treatment indications, Totect is the Food and Drug Administration-approved product for anthracycline extravasations. Facilities administering anthracyclines should proactively resolve how to obtain, process, prepare, and administer this antidote to a patient within 6 hours of an extravasation event. Developing a preprinted chemotherapy extravasation order may facilitate the incorporation of the most recent Oncology Nursing Society guidelines to utilize dexrazoxane for an anthracycline extravasation. Cost sharing with other institutions may offer a creative solution to lessen the financial impact of stocking dexrazoxane therapy. CONCLUSIONS: Ensuring expedient treatment and accessibility to dexrazoxane therapy after an anthracycline extravasation is critical to the success of the treatment. All facilities utilizing anthracycline chemotherapy should purchase dexrazoxane or secure agreements with other facilities to guarantee the administration of this medication should extravasation occur.
Risk of Venous Thromboembolism with Drospirenone in Combined Oral Contraceptive Products
Authors: Sehovic Naida , Smith Katherine P 
Published: April 2010

OBJECTIVE: To review primary literature regarding the risk of venous thromboembolism (VTE) in users of combined oral contraceptives (COCs) containing drospirenone compared to COCs containing other progestins. DATA SOURCES: A literature search of MEDLINE and EMBASE (1950-January 2010) was conducted using the following search terms: VTE, thrombosis, thromboembolism, COC, combined hormonal contraceptives, drospirenone, Yasmin, and Yaz. Additional references were retrieved from reference citations. STUDY SELECTION AND DATA EXTRACTION: All English-language primary literature studies were evaluated for relevance. Five studies were identified for evaluation: 1 prescription event monitoring study, 2 prospective postmarketing cohort studies, 1 validation study, and 1 retrospective cohort study. DATA SYNTHESIS: Use of a COC is associated with a 3- to 6-fold increase in VTE risk compared to nonuse. This risk may vary among different oral contraceptives due to the progestin component. Studies evaluated showed that women utilizing a drospirenone-containing COC did not have a higher risk of VTE when compared to women utilizing other progestins. The crude incidence rate ratio for VTE in women taking a COC containing drospirenone compared to a COC containing other progestins ranged from 0.9 to 1.7 (95% CI 0.5 to 2.4). While the studies evaluating VTE risk were mostly large and long term, most failed to consider important risk factors for VTE such as prolonged immobility, obesity, smoking history, and family history of VTE (which could suggest a genetic predisposition to thrombotic events). It was also unclear with some of the studies whether equivalent estrogen doses were used in the comparisons. CONCLUSIONS: Several studies have evaluated the risk of VTE in users of COC-containing drospirenone compared with other progestins, and none were able to show a significantly increased risk of VTE with drospirenone. The recent media attention regarding VTE risk and drospirenone-containing COCs does not seem to be well supported by the research currently available.
Raltegravir Plasma Concentrations in Treatment-Experienced Patients Receiving Salvage Regimens Based on Raltegravir with and without Maraviroc Coadministration
Authors: Baroncelli Silvia , Villani Paola , Weimer Liliana E , Ladisa Nicoletta , Francisci Daniela , Tommasi Chiara , Vullo Vincenzo , Preziosi Roberta , Cicalini Stefania , Cusato Maria , Galluzzo Clementina M , Floridia Marco , Regazzi Mario 
Published: April 2010

BACKGROUND: Raltegravir and maraviroc represent new, important resources for HIV-infected patients with intolerance or resistance to other antiretroviral agents. The safety and efficacy of both drugs have been investigated, but there is no information on possible pharmacokinetic interactions between these 2 drugs in clinical practice. OBJECTIVE: To evaluate raltegravir plasma concentrations in heavily treatment-experienced patients receiving salvage regimens and explore, in a preliminary assessment, the potential influence of maraviroc coadministration and other cofactors on raltegravir trough concentrations (Ctrough). METHODS: Fifty-four HIV-infected patients with triple class (nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, protease inhibitor) treatment experience starting raltegravir 400 mg twice daily, with (n = 11) or without (n = 43) concomitant maraviroc 300 mg twice daily, were evaluated. All regimens included at least 3 drugs of at least 2 different classes. Raltegravir plasma Ctrough, after at least 1 month of treatment, were analyzed to compare groups of patients taking raltegravir only and raltegravir plus maraviroc. Immunovirological (CD4, HIV-RNA) and clinical data after 6 months of treatment were also collected and described. RESULTS: Raltegravir plasma Ctrough showed a large variability (range <0.020-2.47 μg/mL). Median levels were similar in the 2 groups (raltegravir + maraviroc 0.104 μg/mL, range 0.025−0.826; raltegravir 0.090 μg/mL, range <0.020-2.47, p = 0.400). Detectable (>0.02 μg/mL) raltegravir concentrations were observed in all patients receiving raltegravir + maraviroc and in 74% of patients receiving raltegravir alone (p = 0.060). After 6 months of treatment, the 2 groups had similar clinical, virologic, and immunologic conditions. CONCLUSIONS: Coadministration of maraviroc does not seem to have any relevant effects on raltegravir plasma Ctrough in heavily treatment-experienced patients receiving salvage regimens. Further studies should evaluate the potential additional benefits of maraviroc coadministration in terms of virologic and immunologic response.
High-Dose Continuous Infusion β-Lactam Antibiotics for the Treatment of Resistant Pseudomonas Aeruginosa Infections in Immunocompromised Patients
Authors: Moriyama Brad , Henning Stacey A , Childs Richard , Holland Steven M , Anderson Victoria L , Morris John C , Wilson Wyndham H , Drusano George L , Walsh Thomas J 
Published: April 2010

OBJECTIVE: To report a case series of high-dose continuous infusion β-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. CASE SUMMARY: Continuous infusion ceftazidime or aztreonam was administered to achieve target drug concentrations at or above the minimum inhibitory concentration, when possible, in 3 patients with P. aeruginosa infections. The maximal calculated target drug concentration was 100 mg/L. In the first patient, with primary immunodeficiency, neutropenia, and aggressive cutaneous T-cell lymphoma/leukemia, continuous infusion ceftazidime (6.5-9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient, with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient, with severe aplastic anemia, continuous infusion ceftazidime (7-16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. DISCUSSION: Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy, when no other options are available, is the continuous infusion of existing β-lactam antibiotics to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in 3 chronically immunocompromised patients. CONCLUSIONS: Continuous infusion β-lactam antibiotics are a potentially useful treatment strategy for resistant P.aeruginosa infections in immunocompromised patients.
Adverse Drug Reactions in Hospitalized Psychiatric Patients
Authors: Thomas Michele , Boggs Angela A , DiPaula Bethany , Siddiqi Shahida 
Published: April 2010

BACKGROUND: Reducing adverse drug reactions (ADRs) is a critical element in providing safe medication use to hospitalized patients. There is an abundance of literature describing ADRs and preventable ADRs (pADRs) in hospitalized patients; however, little has been published specific to psychiatric inpatients. Further knowledge of the most common pADRs in hospitalized psychiatric patients will allow targeted patient safety initiatives to be developed. OBJECTIVE: To determine the most frequent ADRs and pADRs in a psychiatric hospital, with emphasis on identifying factors for prevention. METHODS: Three years of ADRs at a psychiatric hospital were analyzed and evaluated according to type of medication, preventability, severity, and factors associated with preventability. RESULTS: From July 1, 2006, to June 30, 2009, 93 ADRs were reported; 19 (20.4%) were classified as preventable. Psychiatric medications accounted for 45 (48.4%) of the ADRs and nonpsychiatric medications were associated with 48 (51.6%). Cardiovascular agents (n = 17) and antiepileptics (n = 17) were responsible for most ADRs. Of the 19 pADRs, lithium was the drug reported most frequently, followed by phenytoin and anxiolytics. Nine (47%) of the pADRs were severe and required a medical transfer for management; 3 of the 9 were lithium toxicity. The most common preventability factor involved drug interactions. A pharmacy intervention involving staff education to reduce lithium pADRs is presented. CONCLUSIONS: Awareness of the most frequent drug classes associated with ADRs and pADRs in a psychiatric hospital allows opportunity for education, medication management system changes, and improved patient safety. Lithium, followed by phenytoin and anxiolytics, were the most common drugs associated with pADRs. A drug-drug interaction was the most frequent factor associated with pADRs.
Involvement of the calcium sensor GCAP1 in hereditary cone dystrophies
Authors: Behnen Petra , Dell'Orco Daniele , Koch Karl-Wilhelm 
Published: April 2010

Abstract
Progressive visual impairment leading to blindness is often associated with inherited retinal dystrophies. These disorders correlate in most cases with mutations in genes that code for proteins of the visual transduction system in rod and cone photoreceptor cells. Recent progress has highlighted the involvement of a neuronal calcium sensor protein that is specifically expressed in rod and cone cells and operates as a guanylate cyclase-activating protein (GCAP). A group of patients suffering from cone or cone-rod dystrophies carry mutations in the GCAP1 gene, and biochemical analysis of GCAP1 function revealed that for most of these mutations GCAP1 exhibits a disturbance in its Ca2+-sensing and its guanylate cyclase-activating properties. Cellular consequences of different GCAP1 mutations are compared and discussed.
RIM proteins and their role in synapse function
Authors: Mittelstaedt Tobias , Alvaréz-Baron Elena , Schoch Susanne 
Published: April 2010

Abstract
Active zones are specialized areas of the plasma membrane in the presynaptic nerve terminal that mediate neurotransmitter release and synaptic plasticity. The multidomain proteins RIM1 and RIM2 are integral components of the cytomatrix at the active zone, interacting with most other active zone-enriched proteins as well as synaptic vesicle proteins. In the brain, RIMs are present in multiple isoforms (α, β, γ) diverging in their structural composition, which mediate overlapping and distinct functions. Here, we summarize recent findings about the specific roles of the various RIM isoforms in basic synaptic vesicle release as well as long- and short-term presynaptic plasticity.
Cathepsin L in metastatic bone disease: therapeutic implications
Authors: Leto Gaetano , Sepporta Maria Vittoria , Crescimanno Marilena , Flandina Carla , Tumminello Francesca Maria 
Published: April 2010

AbstractCathepsin L is a lysosomal cysteine proteinase primarily devoted to the metabolic turnover of intracellular proteins. However, accumulating evidence suggests that this endopeptidase might also be implicated in the regulation of other important biological functions, including bone resorption in normal and pathological conditions. These findings support the concept that cathepsin L, in concert with other proteolytic enzymes involved in bone remodeling processes, could contribute to facilitate bone metastasis formation. In support of this hypothesis, recent studies indicate that cathepsin L can foster this process by triggering multiple mechanisms which, in part, differ from those of the major cysteine proteinase of osteoclasts, namely cathepsin K. Therefore, cathepsin L can be regarded as an additional target in the treatment of patients with metastatic bone disease. This review discusses the clinical and therapeutic implications related to these findings.