tbuckley/cabot-search huggingface dataset:
Cochrane review: post-operative procedures for improving fertility following pelvic reproductive surgery
Authors: N.P. Johnson
Journal: Human Reproduction Update (2000)

The objectives of the study was to determine the effectiveness of post-operative procedures following female pelvic reproductive surgery. A systematic review employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was used. Five randomized controlled trials were included. Participants were women undergoing pelvic reproductive surgery; interventions were any post-operative procedure designed to improve fertility; outcomes were pregnancy, live birth, ectopic pregnancy and miscarriage rates and the rates of tubal patency and procedure-related complications. Summary statistics were expressed as odds ratios. The results showed that the odds of pregnancy, live birth, ectopic pregnancy and miscarriage were not significantly altered by post-operative hydrotubation nor second-look laparoscopy with adhesiolysis. Whether hydrotubation was early or late and whether hydrotubation fluid contained steroid or not had no significant impact on the odds of pregnancy, live birth, ectopic pregnancy or miscarriage. The odds of pregnancy and live birth were significantly increased and infective complications significantly decreased by hydrotubation with fluid containing antibiotic compared with hydrotubation with fluid containing no antibiotic, in late hydrotubation following tubal stent removal 6 weeks after tubal surgery. The odds of at least one patent Fallopian tube were significantly increased with late hydrotubation following tubal stent removal compared with early hydrotubation in women who had no tubal stenting, but this intervention had no significant impact on the odds of pregnancy, live birth, ectopic pregnancy or miscarriage. In conclusion, there is insufficient evidence to support the routine practice of hydrotubation or second-look laparoscopy following female pelvic reproductive surgery. The studies on which this conclusion is based were either poor quality or underpowered. Post-operative hydrotubation with fluid containing antibiotic following tubal surgery may offer benefit over hydrotubation fluid without antibiotic. A randomized controlled trial of post-operative hydrotubation with antibiotic-containing fluid versus no hydrotubation for improving fertility following tubal surgery is justified.
Combined Treatment of Pancreatic Cancer with Mithramycin A and Tolfenamic Acid Promotes Sp1 Degradation and Synergistic Antitumor Activity
Authors: Zhiliang Jia, Yong Gao, Liwei Wang, Qiang Li, Jun Zhang, Xiangdong Le, Daoyan Wei, James C. Yao, David Z. Chang, Suyun Huang, Keping Xie
Journal: Cancer Research (2010)

Mithramycin (MIT) and tolfenamic acid (TA) inhibit the activity of the transcription factor Sp1. In the present study, we investigated whether pancreatic cancer treatment with a combination of these compounds has a synergistic effect on Sp1 activity, tumor growth, and their underlying response mechanisms. Treatment of pancreatic tumor xenografts with MIT and TA produced dose-dependent antitumor activity, and significant antitumor activity of either compound alone was directly associated with systemic side effects. Combination treatment with nontoxic doses of both compounds produced synergistic antitumor activity, whereas treatment with a nontoxic dose of either compound alone lacked a discernible antitumor effect. Synergistic therapeutic effects correlated directly with synergistic antiproliferation and antiangiogenesis in vitro. Moreover, combination treatment resulted in Sp1 protein degradation, drastically downregulating expression of Sp1 and vascular endothelial growth factor. Our findings established that Sp1 is a critical target of TA and MIT in human pancreatic cancer therapy, rationalizing clinical studies to determine the effect of existing pancreatic cancer therapy regimens on Sp1 signaling in tumors and normal pancreatic tissue, and the ability of Sp1-targeting strategies to modify cancer responses.
Soluble Epoxide Hydrolase Regulates Hydrolysis of Vasoactive Epoxyeicosatrienoic Acids
Authors: Zhigang Yu, Fengyun Xu, Linn M. Huse, Christophe Morisseau, Alison J. Draper, John W. Newman, Carol Parker, LeRae Graham, Marguerite M. Engler, Bruce D. Hammock, Darryl C. Zeldin, Deanna L. Kroetz
Journal: Circulation Research (2000)

Abstract —The cytochrome P450-derived epoxyeicosatrienoic acids (EETs) have potent effects on renal vascular reactivity and tubular sodium and water transport; however, the role of these eicosanoids in the pathogenesis of hypertension is controversial. The current study examined the hydrolysis of the EETs to the corresponding dihydroxyeicosatrienoic acids (DHETs) as a mechanism for regulation of EET activity and blood pressure. EET hydrolysis was increased 5- to 54-fold in renal cortical S9 fractions from the spontaneously hypertensive rat (SHR) relative to the normotensive Wistar-Kyoto (WKY) rat. This increase was most significant for the 14,15-EET regioisomer, and there was a clear preference for hydrolysis of 14,15-EET over the 8,9- and 11,12-EETs. Increased EET hydrolysis was consistent with increased expression of soluble epoxide hydrolase (sEH) in the SHR renal microsomes and cytosol relative to the WKY samples. The urinary excretion of 14,15-DHET was 2.6-fold higher in the SHR than in the WKY rat, confirming increased EET hydrolysis in the SHR in vivo. Blood pressure was decreased 22±4 mm Hg ( P &lt;0.01) 6 hours after treatment of SHRs with the selective sEH inhibitor N , N ′-dicyclohexylurea; this treatment had no effect on blood pressure in the WKY rat. These studies identify sEH as a novel therapeutic target for control of blood pressure. The identification of a potent and selective inhibitor of EET hydrolysis will be invaluable in separating the vascular effects of the EET and DHET eicosanoids.
Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death
Authors: Christopher M. Heaphy, Ghil Suk Yoon, Sarah B. Peskoe, Corinne E. Joshu, Thomas K. Lee, Edward Giovannucci, Lorelei A. Mucci, Stacey A. Kenfield, Meir J. Stampfer, Jessica L. Hicks, Angelo M. De Marzo, Elizabeth A. Platz, Alan K. Meeker
Journal: Cancer Discovery (2013)

Current prognostic indicators are imperfect predictors of outcome in men with clinically localized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study. Men who had the combination of more variable telomere length among prostate cancer cells (cell-to-cell) and shorter telomere length in prostate cancer-associated stromal (CAS) cells were substantially more likely to progress to metastasis or die of their prostate cancer. These findings point to the translational potential of this telomere biomarker for prognostication and risk stratification for individualized therapeutic and surveillance strategies.In this prospective study, the combination of more variable telomere length among cancer cells and shorter telomere length in CAS cells was strongly associated with progression to metastasis and prostate cancer death, pointing to the translational potential for prognostication and risk stratifi cation for individualized therapeutic and surveillance strategies.
Assessment of Barriers to Improve Diabetes Management in Older Adults
Authors: Medha N. Munshi, Alissa R. Segal, Emmy Suhl, Courtney Ryan, Adrianne Sternthal, Judy Giusti, Yishan Lee, Shane Fitzgerald, Elizabeth Staum, Patricia Bonsignor, Laura DesRochers, Richard McCartney, Katie Weinger
Journal: Diabetes Care (2012)

To evaluate whether assessment of barriers to self-care and strategies to cope with these barriers in older adults with diabetes is superior to usual care with attention control. The American Diabetes Association guidelines recommend the assessment of age-specific barriers. However, the effect of such strategy on outcomes is unknown.We randomized 100 subjects aged ≥69 years with poorly controlled diabetes (A1C >8%) in two groups. A geriatric diabetes team assessed barriers and developed strategies to help patients cope with barriers for an intervention group. The control group received equal amounts of attention time. The active intervention was performed for the first 6 months, followed by a "no-contact" period. Outcome measures included A1C, Tinetti test, 6-min walk test (6MWT), self-care frequency, and diabetes-related distress.We assessed 100 patients (age 75 ± 5 years, duration 21 ± 13 years, 68% type 2 diabetes, 89% on insulin) over 12 months. After the active period, A1C decreased by -0.45% in the intervention group vs. -0.31% in the control group. At 12 months, A1C decreased further in the intervention group by -0.21% vs. 0% in control group (linear mixed-model, P < 0.03). The intervention group showed additional benefits in scores on measures of self-care (Self-Care Inventory-R), gait and balance (Tinetti), and endurance (6MWT) compared with the control group. Diabetes-related distress improved in both groups.Only attention between clinic visits lowers diabetes-related distress in older adults. However, communication with an educator cognizant of patients' barriers improves glycemic control and self-care frequency, maintains functionality, and lowers distress in this population.
Expression of αB-crystallin overrides the anti-apoptotic activity of XIAP
Authors: Jee Suk Lee, Hye Young Kim, Na Young Jeong, Sang Yeob Lee, Young Geol Yoon, Yung Hyun Choi, Chunlan Yan, In-Sun Chu, Hyungjong Koh, Hwan Tae Park, Young Hyun Yoo
Journal: Neuro-Oncology (2012)

Although crystallins are major structural proteins in the lens, α-crystallins perform non-lens functions, and αB-crystallin has been shown to act as an anti-apoptotic mediator in various cells. The present study was undertaken to examine whether αB-crystallin expressed in human malignant glioma cells exerts anti-apoptotic acitivity. In addition, we sought to elucidate the mechanism underlying any observed anti-apoptotic function of αB-crystallin in these cells. Three glioma cell lines, U373MG, U118MG, and T98G, were used. We observed that only the U373MG cell line expresses αB-crystallin, whereas the other 2 glioma cell lines, U118MG and T98G, demonstrated no endogenous expression of αB-crystallin. We next observed that the silencing of αB-crystallin sensitized U373MG cells to suberoylanilide hydroxamic acid (SAHA)–induced apoptosis and that αB-crystallin associates with caspase-3 and XIAP. Because XIAP is the most potent suppressor of mammalian apoptosis through the direct binding with caspases, we assessed whether XIAP also plays an anti-apoptotic role in SAHA-induced apoptosis in αB-crystallin-expressing U373MG cells. Of note, the silencing of XIAP did not alter the amount of cell death induced by SAHA, indicating that XIAP does not exert an anti-apoptotic activity in U373MG cells. We then determined whether the ectopic expression of αB-crystallin in glioma cells caused a loss of the anti-apoptotic activity of XIAP. Accordingly, we established 2 αB-crystallin over-expressing glioma cell lines, U118MG and T98G, and found that the silencing of XIAP did not sensitize these cells to SAHA-induced apoptosis. These findings suggest that αB-crystallin expressed in glioma cells overrides the anti-apoptotic activity exerted by XIAP.
Interpreting Trends in Prostate Cancer Incidence and Mortality in the Five Nordic Countries
Authors: R. Kvale, A. Auvinen, H.-O. Adami, A. Klint, E. Hernes, B. Moller, E. Pukkala, H. H. Storm, L. Tryggvadottir, S. Tretli, R. Wahlqvist, E. Weiderpass, F. Bray
Journal: JNCI Journal of the National Cancer Institute (2007)

Trends in incidence and mortality rates of prostate cancer were analyzed using data from the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden. Joinpoint regression models were used to quantify temporal trends for the period from 1980 to 2004. Incidence rates were increasing and similar in the Nordic countries during the 1980s. Around 1990, a more rapid incidence increase began in all Nordic countries except Denmark, where an increase was seen 5 years later. In 2001, incidence rates in Denmark were half of those seen in the other Nordic countries, but mortality rates varied only marginally among countries. Mean annual declines in prostate cancer mortality of 1.9% (95% CI = 0.4% to 3.3%) and 1.8% (95% CI = 0.5% to 3.0%) were observed from 1996 to 2004 in Finland and Norway, respectively. During the same period, mortality rates leveled off in Iceland and Sweden but continued to increase in Denmark. The rapid increase in incidence during the early 1990s coincided with the introduction of the prostate-specific antigen (PSA) test and conveys little information about the occurrence of potentially lethal disease. Mortality rates, however, have recently stabilized or declined in countries where PSA testing and curative treatment have been commonly practiced since the late 1980s. Although other explanatory factors may be in operation, these trends are consistent with a moderate effect of increased curative treatment of early diagnosed prostate cancer and improved treatment of more advanced disease.
Sacral Rhizotomies and Electrical Bladder Stimulation in Spinal Cord Injury
Authors: Ph.E.V. Van Kerrebroeck, H.E. van der Aa, J.L.H.R. Bosch, E.L. Koldewijn, J.H.C. Vorsteveld, F.M.J. Debruyne
Journal: European Urology (1997)
Elevated CD4+/CD25+ T cell frequency and function during acute hepatitis C presage chronic evolution
Authors: A Perrella
Journal: Gut (2006)

Hepatitis C virus (HCV) determines an acute hepatitis evolving to persistent infection in 50–80% of patients.1 Different mechanisms have been proposed to explain disease evolution, including viral escape, failure of the T helper immune network, and host genetic factors.2 Among CD4+ T cell subsets, lymphocytes expressing constitutively CD25 (interleukin 2 receptor alpha chain), namely T regulatory cells (Treg), appear to play a critical role in controlling chronic evolution of HCV mediated liver diseases.3 Here we investigate the frequency and functional activity of CD3+/CD4+/CD25+ Tregs in acute HCV infection in relation to its evolution over time.

The study was approved by the local ethics committee and included 16 consecutive patients with acute hepatitis C (AHC), 15 consecutive patients with acute hepatitis A (AHA), and …
Capreomycin-induced serum electrolyte abnormalities
Authors: A. M. Holmes, C. M. Hesling, T. M. Wilson
Journal: Thorax (1970)

Gross electrolyte disturbances including hypokalaemia, hypomagnesaemia, hypocalcaemia, and alkalosis have developed in tuberculous patients who were being treated with capreomycin. Similar abnormalities have also occurred when the drug gentamicin was used and were found to be due to secondary hyperaldosteronism. In this paper a detailed description of the changes induced by capreomycin is given. The evidence available strongly suggests a similar aetiology for the biochemical changes, but the precise pathophysiology is unknown. Caution should be exercised when capreomycin is used and the drug should be withdrawn if any of these abnormalities develop.
2-Arachidonoyl glycerol induces contraction of isolated rat aorta: role of cyclooxygenase-derived products
Authors: F STANKELABESQUE, M MALLARET, B LEFEBVRE, G HARDY, F CARON, G BESSARD
Journal: Cardiovascular Research (2004)

Endocannabinoids have been shown to play a role in the regulation of vascular tone. The effects of 2-arachidonoyl glycerol (2-AG) on induced-tone were examined in rat aortic rings in vitro.Aortic rings from Wistar Kyoto (WKY) rats were suspended in organ chambers for recording isometric tension development in response to 2-AG. The production of TXA2 in response to 2-AG was also assessed by enzyme immunoassay.In endothelium-intact rings pre-contracted to PGF(2alpha), 2-AG (10 nM-30 microM) induced a biphasic effect: a weak relaxation from 10 nM to 0.1 microM, which turned into a concentration-dependent contraction from 3 to 30 microM. Endothelium-denudation did not change 2-AG-mediated vascular effects. 2-AG-induced contraction was unaffected by both the cannabinoid CB1 receptor antagonist SR141716A (3 microM) and the CB2 receptor antagonist SR144528 (1 microM). In contrast, the anandamine transport inhibitor (AM404, 100 microM) and the amino hydrolase inhibitor (PMSF, 30 microM) attenuated (P<0.05) the contractile response evoked by 2-AG in endothelium-intact and rubbed aortic rings. In addition, the cyclooxygenase inhibitor (indomethacin, 10 microM) and the thromboxane A2 (TXA2) receptor (TP receptor) antagonist GR32191 (0.3 microM) totally abolished the contraction elicited by 2-AG in endothelium-intact and rubbed aortic rings. Challenge of isolated aortic rings with 2-AG (10 microM) evoked a significant increase in TXA2 level (measured as TXB2 level) in endothelium-intact and rubbed aortic rings.These data suggested that the contraction elicited by 2-AG resulted from the vascular smooth muscle cell uptake and conversion of 2-AG to constrictor prostanoid TXA2, which in turn caused vasoconstriction through the stimulation of TP receptor.
Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: A phase II study of the Greek Cooperative Group for Pancreatic Cancer
Authors: G.P. Stathopoulos, D. Mavroudis, N. Tsavaris, C. Kouroussis, G. Aravantinos, S. Agelaki, S. Kakolyris, S.K. Rigatos, S. Karabekios, V. Georgoulias
Journal: Annals of Oncology (2001)
Acute effect of percutaneous transvenous mitral commissurotomy on ventilatory and hemodynamic responses to exercise. Pathophysiological basis for early symptomatic improvement.
Authors: Y Tanabe, M Suzuki, M Takahashi, M Oshima, Y Yamazaki, T Yamaguchi, Y Igarashi, Y Tamura, M Yamazoe, A Shibata
Journal: Circulation (1993)

BACKGROUND Improvement of exertional dyspnea occurs immediately after percutaneous transvenous mitral commissurotomy (PTMC), but the pathophysiological basis for this early symptomatic improvement has not been elucidated. METHODS AND RESULTS Exercise hemodynamic measurement and exercise ventilatory measurement with arterial blood gas analysis were performed in 21 patients aged 50.4 +/- 9.5 years (mean +/- SD) with symptomatic mitral stenosis before and a few days after PTMC. Exercise ventilatory measurement were also performed in 14 normal control subjects aged 48.9 +/- 4.9 years. After PTMC, mitral valve area increased (from 1.0 +/- 0.3 to 1.7 +/- 0.3 cm2, P &lt; .001), mean mitral gradient (from 12.2 +/- 5.2 to 5.2 +/- 2.2 mm Hg, P &lt; .001), and mean left atrial pressure (from 18.7 +/- 6.1 to 12.1 +/- 4.0 mm Hg, P &lt; .001) decreased. All patients experienced significant symptomatic improvement soon after PTMC. Comparison of hemodynamic parameters at the same ergometer work rate showed a significant decrease in pulmonary artery systolic pressure (from 77 +/- 18 to 67 +/- 14 mm Hg, P &lt; .001) and diastolic pressure (from 36 +/- 10 to 28 +/- 7 mm Hg, P &lt; .001) and a significant increase in cardiac output (from 6.4 +/- 1.4 to 8.1 +/- 1.9 L/min, P &lt; .001). Despite the improvement in exercise hemodynamics and symptoms, exercise capacity determined by peak oxygen uptake (from 18.0 +/- 2.9 to 18.6 +/- 3.1 mL.kg-1 x min-1) and anaerobic threshold (from 11.7 +/- 2.4 to 12.0 +/- 2.4 mL.kg-1 x min-1) remained unchanged. Excessive exercise ventilation, as assessed by the slope of the regression line between expired minute ventilation and carbon dioxide output, decreased significantly from 37.2 +/- 6.7 to 33.9 +/- 5.8 (P &lt; .001), but remained significantly higher than that in the normal subjects (27.9 +/- 3.6, P &lt; .01). The ratio of total dead space to tidal volume and total dead space per breath during exercise decreased significantly after PTMC (P &lt; .05). The change in excessive exercise ventilation after PTMC was correlated with the change in dead space to tidal volume ratio (r = .59). CONCLUSIONS Significant relief of exertional dyspnea immediately after PTMC is not accompanied by an improvement in exercise capacity. A decrease in excessive ventilation due to a decrease in physiological dead space resulting from hemodynamic improvement partly contributes to the early relief of symptoms after PTMC. However, lung compliance, which was not measured in the present study, may have changed after PTMC. This change may also contribute to the symptomatic improvement.
Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial
Authors: J Athene Lane, Jenny L Donovan, Michael Davis, Eleanor Walsh, Daniel Dedman, Liz Down, Emma L Turner, Malcolm D Mason, Chris Metcalfe, Tim J Peters, Richard M Martin, David E Neal, Freddie C Hamdy
Journal: The Lancet Oncology (2014)

Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options. We report the study design, participant sociodemographic and clinical characteristics, and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment (ProtecT) trial, which aims to investigate the effectiveness of treatments for localised prostate cancer.
Low Intraindividual Variability of Cyclosporin A Exposure Reduces Chronic Rejection Incidence and Health Care Costs
Authors: BARRY D. KAHAN, MARIA WELSH, DIANA L. URBAUER, MELINDA B. MOSHEIM, KATHLEEN M. BEUSTERIEN, MARTHA R. WOOD, LINDA P. SCHOENBERG, JOSEPH DICESARE, STEPHEN M. KATZ, CHARLES T. VAN BUREN
Journal: Journal of the American Society of Nephrology (2000)

The present study applied a receiver operating characteristic (ROC) analysis to assess the role of intraindividual variability of cyclosporin A (CsA) drug exposure in predisposing renal transplant recipients to the occurrence of chronic rejection, as well as to increased health care costs using a resource-based economic analysis. Two hundred and four adult renal transplant recipients were treated with tapering doses of prednisone (Pred) and with a concentration-controlled strategy that selected doses of the olive oil-based formulations of CsA (Sandimmune(R)) that achieved target concentrations based on serial pharmacokinetic profiles. The ROC analysis revealed an inflection point of plots of the coefficient of variation (%CV) of CsA exposure versus the risk of chronic rejection at >/=28.4% for the average concentration (C(av)), i.e., the dosing interval-corrected area under the concentration-time curves, and >/=36% for the trough concentration (C(0)). The incidence of chronic rejection over a period of 5 yr was 24% among the less variable (LV) versus 40% among the variable (V) cohort. The economic analysis revealed that the total mean facility and physician costs per patient were $48,789 versus $60,998, respectively (P < 0.01). The degree of variability displayed by any individual could only be predicted by serial measurements of CsA concentrations, and not by demographic features, laboratory determinations, clinical characteristics, individual or mean values of any observed CsA concentration, or other pharmacokinetic parameters calculated following a single drug exposure. Thus, strategies that reduce intrapatient variability of CsA exposure over time may lead to reductions in chronic allograft loss and in treatment costs.