tbuckley/cabot-search huggingface dataset:
Cardiovascular Risk Factors and Disease Management in Type 2 Diabetic Patients With Diabetic Nephropathy
Authors: Ferdinando C. Sasso, Luca De Nicola, Ornella Carbonara, Rodolfo Nasti, Roberto Minutolo, Teresa Salvatore, Giuseppe Conte, Roberto Torella
Journal: Diabetes Care (2006)

OBJECTIVE—The purpose of this study was to assess the prevalence of cardiorenal risk factors, their management in a routine clinical setting, and the actual achievement of international guideline targets in a large cohort of type 2 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS—A multicentric cross-sectional study was performed in the Campania region in Italy to evaluate cardiorenal risk factors and their management in light of international guidelines. Overall, 28,550 diabetic patients were screened in the 21 participating centers; 847 (348 male and 449 female) patients with type 2 diabetes and a clinical diagnosis of diabetic nephropathy were recruited. RESULTS—Of these subjects, 749 had microalbuminuria and 98 had macroalbuminuria. Targets for blood pressure, HbA1c, LDL cholesterol, HDL cholesterol, and triglycerides were reached in, respectively, 17.5, 32.3, 30.7, 47, and 55.2% of the patients. Chronic renal failure (glomerular filtration rate &amp;lt;60 ml/min) was revealed in 41% and anemia in 23.8% of the patients. CONCLUSIONS—This is the first study to investigate a large cohort of type 2 diabetic patients with early and moderate diabetic nephropathy strictu sensu. Notably, impaired renal function can be often diagnosed in these patients even in the presence of microalbuminuria. Thus, clinical diagnosis of diabetic nephopathy allows us to identify a group of patients at very high cardiorenal risk, for whom care is really difficult. We suggest that a correct diagnosis of diabetic nephropathy should always be made and that sodium intake and anemia should be routinely evaluated in these patients.
Effect of guideline based computerised decision support on decision making of multidisciplinary teams: cluster randomised trial in cardiac rehabilitation
Authors: R. Goud, N. F de Keizer, G. ter Riet, J. C Wyatt, A. Hasman, I. M Hellemans, N. Peek
Journal: BMJ (2009)

<b>Objective</b> To determine the extent to which computerised decision support can improve concordance of multidisciplinary teams with therapeutic decisions recommended by guidelines. <b>Design</b> Multicentre cluster randomised trial. <b>Participants</b> Multidisciplinary cardiac rehabilitation teams in Dutch centres and their cardiac rehabilitation patients. <b>Interventions</b> Teams received an electronic patient record system with or without additional guideline based decision support. <b>Main outcome measures</b> Concordance with guideline recommendations assessed for two standard rehabilitation treatments—exercise and education therapy—and for two new but evidence based rehabilitation treatments—relaxation and lifestyle change therapy; generalised estimating equations were used to account for intra-cluster correlation and were adjusted for patient's age, sex, and indication for cardiac rehabilitation and for type and volume of centre. <b>Results</b> Data from 21 centres, including 2787 patients, were analysed. Computerised decision support increased concordance with guideline recommended therapeutic decisions for exercise therapy by 7.9% (control 84.7%; adjusted difference 3.5%, 95% confidence 0.1% to 5.2%), for education therapy by 25.7% (control 63.9%; adjusted difference 23.7%, 15.5% to 29.4%), and for relaxation therapy by 25.5% (control 34.1%; adjusted difference 41.6%, 25.2% to 51.3%). The concordance for lifestyle change therapy increased by 3.2% (control 54.1%; adjusted difference 7.1%, −2.9% to 18.3%). Computerised decision support reduced cases of both overtreatment and undertreatment. <b>Conclusions</b> In a multidisciplinary team motivated to adopt a computerised decision support aid that assists in formulating guideline based care plans, computerised decision support can be effective in improving the team's concordance with guidelines. Therefore, computerised decision support may also be considered to improve implementation of guidelines in such settings. <b>Trial registration</b> Current Controlled Trials ISRCTN36656997.
Combined Effect of Proteasome and Calpain Inhibition on Cisplatin-Resistant Human Melanoma Cells
Authors: Izabela Młynarczuk-Biały, Heike Roeckmann, Ulrike Kuckelkorn, Boris Schmidt, Sumaira Umbreen, Jakub Gołąb, Antje Ludwig, Christina Montag, Lüder Wiebusch, Christian Hagemeier, Dirk Schadendorf, Peter-M. Kloetzel, Ulrike Seifert
Journal: Cancer Research (2006)

Abstract Resistance of tumor cells to cisplatin is a common feature frequently encountered during chemotherapy against melanoma caused by various known and unknown mechanisms. To overcome drug resistance toward cisplatin, a targeted treatment using alternative agents, such as proteasome inhibitors, has been investigated. This combination could offer a new therapeutic approach. Here, we report the biological effects of proteasome inhibitors on the parental cisplatin-sensitive MeWo human melanoma cell line and its cisplatin-resistant MeWocis1 variant. Our experiments show that proteasome inhibitor treatment of both cell lines impairs cell viability at concentrations that are not toxic to primary human fibroblasts in vitro. However, compared with the parental MeWo cell line, significantly higher concentrations of proteasome inhibitor are required to reduce cell viability of MeWocis1 cells. Moreover, whereas proteasome activity was inhibited to the same extent in both cell lines, IκBα degradation and nuclear factor-κB (NF-κB) activation in MeWocis1 cells was proteasome inhibitor independent but essentially calpain inhibitor sensitive. In support, a calpain-specific inhibitor impaired NF-κB activation in MeWocis1 cells. Here, we show that cisplatin resistance in MeWocis1 is accompanied by a change in the NF-κB activation pathway in favor of calpain-mediated IκBα degradation. Furthermore, combined exposure to proteasome and calpain inhibitor resulted in additive effects and a strongly reduced cell viability of MeWocis1 cells. Thus, combined strategies targeting distinct proteolytic pathways may help to overcome mechanisms of drug resistance in tumor cells. (Cancer Res 2006; 66(15): 7598-605)
The use of different induction and maintenance chemotherapy regimens for the treatment of advanced yolk sac tumors.
Authors: D M Green, M L Brecher, M Grossi, L Simpson, J E Fisher, J E Allen, D R Cooney, T C Jewett, A I Freeman
Journal: Journal of Clinical Oncology (1983)

Four children with yolk sac tumor were treated with an aggressive combination chemotherapy program. Three children had presacral primary tumors, one having pulmonary metastases, and one had a testicular primary tumor with pulmonary metastases. Three children were treated when they had measurable disease, and one had no measurable disease. The chemotherapy program consisted of a 6-wk induction period with vincristine (VCR), cis-diamminedichloroplatinum (DDP), and bleomycin. Maintenance therapy consisted of VCR, actinomycin D, and cyclophosphamide (cytoxan) every 3-4 wk as tolerated. Treatment was discontinued after 12 mo of complete remission. All three patients with evaluable disease had a partial response (PR) to induction therapy. Two underwent surgical exploration following induction therapy, one a laparotomy and the other a thoracotomy, and were found to have only scar tissue at the sites of presumed residual disease. The third child with measurable disease progressed to a clinical complete response (CR) during maintenance therapy. Two patients have had no evidence of disease (NED) for 42+ and 41+ mo since starting therapy (28+ and 27+ mo since completing treatment). Two patients are NED 11+ and 7+ mo since starting therapy and remain on treatment. We have encountered no significant renal or pulmonary toxicity, and there have been only two hospitalizations during maintenance therapy for fever and neutropenia. These preliminary results employing different induction and maintenance chemotherapy programs and planned second-look surgical intervention appear encouraging.
Altered DNA Polymerase ι Expression in Breast Cancer Cells Leads to a Reduction in DNA Replication Fidelity and a Higher Rate of Mutagenesis
Authors: Jin Yang, Zhiwen Chen, Yang Liu, Robert J. Hickey, Linda H. Malkas
Journal: Cancer Research (2004)

Abstract The recently discovered human enzyme DNA polymerase ι (pol ι) has been shown to have an exceptionally high error rate on artificial DNA templates. Although there is a considerable body of in vitro evidence for a role for pol ι in DNA lesion bypass, there is no in vivo evidence to confirm this action. We report here that pol ι expression is elevated in breast cancer cells and correlates with a significant decrease in DNA replication fidelity. We also demonstrate that UV treatment of breast cancer cells additionally increases pol ι expression with a peak occurring between 30 min and 2 h after cellular insult. This implies that the change in pol ι expression is an early event after UV-mediated DNA damage. That pol ι may play a role in the higher mutation frequencies observed in breast cancer cells was suggested when a reduction in mutation frequency was found after pol ι was immunodepleted from nuclear extracts of the cells. Analysis of the UV-induced mutation spectra revealed that &amp;gt;90% were point mutations. The analysis also demonstrated a decreased C→T nucleotide transition and an increased C→A transversion rate. Overall, our data strongly suggest that pol ι may be involved in the generation of both increased spontaneous and translesion mutations during DNA replication in breast cancer cells, thereby contributing to the accumulation of genetic damage.
Combined effects of As4S4 and imatinib on chronic myeloid leukemia cells and BCR-ABL oncoprotein
Authors: Tong Yin, Ying-Li Wu, Hui-Ping Sun, Guan-Lin Sun, Yan-Zhi Du, Kan-Kan Wang, Ji Zhang, Guo-Qiang Chen, Sai-Juan Chen, Zhu Chen
Journal: Blood (2004)
Early Detection of Malignant Melanoma: The Role of Physician Examination and Self-Examination of the Skin
Authors: R. J. Friedman, D. S. Rigel, A. W. Kopf
Journal: CA A Cancer Journal for Clinicians (1985)

The combination of routine physician examination of the skin coupled with self-examination provides a realistic opportunity for the identification of early malignant melanomas. Removal of such thin lesions can significantly reduce the mortality rate from this potentially serious form of cutaneous cancer.
Risk of hospitalised infection in rheumatoid arthritis patients receiving biologics following a previous infection while on treatment with anti-TNF therapy
Authors: Huifeng Yun, Fenglong Xie, Elizabeth Delzell, Lang Chen, Emily B Levitan, James D Lewis, Kenneth G Saag, Timothy Beukelman, Kevin Winthrop, John W Baddley, Jeffrey R Curtis
Journal: Annals of the Rheumatic Diseases (2014)

Background The risk of subsequent infections in rheumatoid arthritis (RA) patients who receive biologic therapy after a serious infection is unclear. Objective To compare the subsequent risk of hospitalised infections associated with specific biologic agents among RA patients previously hospitalised for infection while receiving anti-tumour necrosis factor (anti-TNF) therapy. Methods Using 2006–2010 Medicare data for 100% of beneficiaries with RA enrolled in Medicare, we identified patients hospitalised with an infection while on anti-TNF agents. Follow-up began 61 days after hospital discharge and ended at the earliest of: next infection, loss of Medicare coverage or 18 months after start of follow-up. We calculated the incidence rate of subsequent hospitalised infection for each biologic and used Cox regression to control for potential confounders. Results 10 794 eligible hospitalised infections among 10183 unique RA patients who contributed at least 1 day of biologic exposure during follow-up. We identified 7807 person-years of exposure to selected biologics—333 abatacept, 133 rituximab and 7341 anti-TNFs (1797 etanercept, 1405 adalimumab, 4139 infliximab)—and 2666 associated infections. Mean age across biologic exposure cohorts was 64–69 years. The crude incidence rate of subsequent hospitalised infection ranged from 27.1 to 34.6 per 100 person-years. After multivariable adjustment, abatacept (HR: 0.80, 95% CI 0.64 to 0.99) and etanercept (HR: 0.83, 95% CI 0.72 to 0.96) users had significantly lower risks of subsequent infection compared to infliximab users. Conclusions Among RA patients who experienced a hospitalised infection while on anti-TNF therapy, abatacept and etanercept were associated with the lowest risk of subsequent infection compared to other biologic therapies.
Avian Precardiac Endoderm/Mesoderm Induces Cardiac Myocyte Differentiation in Murine Embryonic Stem Cells
Authors: Diane Rudy-Reil, John Lough
Journal: Circulation Research (2004)

The ability to regenerate damaged myocardium with tissue derived from embryonic stem (ES) cells is currently undergoing extensive investigation. As a prerequisite to transplantation therapy, strategies must be developed to induce ES cells to the cardiac phenotype. Toward this end, cues from mechanisms of embryonic induction have been exploited, based on previous findings that anterior lateral endoderm (precardiac endoderm) from gastrulation-stage chick embryos potently induces cardiac myocyte differentiation in both precardiac and nonprecardiac mesoderm. Hypothesizing that avian precardiac endoderm acting as feeder/inducer cells would induce high percentage conversion of murine ES (mES) cells into cardiac myocytes, it was observed that the majority (approximately 65%) of cocultured ES cell-derived embryoid bodies (EBs) were enriched in cardiac myocytes and exhibited rhythmic contractions. By contrast, mouse EBs cultured alone, or on feeder layers of mouse embryonic fibroblasts or avian nonprecardiac posterior endoderm, contained only 7% to 16% cardiac myocytes while exhibiting a relatively low incidence (<10%) of beating. When mES cells were cocultured with a bilayer of explanted precardiac endoderm/mesoderm, the incidence of rhythmically contractile EBs increased to 100%. To verify that the rhythmically contractile cells were derived from murine ES cells, cell-free medium conditioned by avian precardiac endoderm/mesoderm was used to induce myocyte differentiation in a mES cell-line containing a nuclear LacZ reporter marker gene under control of the cardiac-specific alpha-myosin heavy chain promoter, resulting in rhythmic contractility in 92% of EBs in which the majority of cells (average=86%) were identified as cardiac myocytes. The inductive efficacy of medium conditioned by avian precardiac endoderm/mesoderm may provide an opportunity to biochemically define factors that induce cardiac myocyte differentiation in ES cells. The full text of this article is available online at http://circres.ahajournals.org.
Most Youth With Type 1 Diabetes in the T1D Exchange Clinic Registry Do Not Meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes Clinical Guidelines
Authors: Jamie R. Wood, Kellee M. Miller, David M. Maahs, Roy W. Beck, Linda A. DiMeglio, Ingrid M. Libman, Maryanne Quinn, William V. Tamborlane, Stephanie E. Woerner
Journal: Diabetes Care (2013)

To assess the proportion of youth with type 1 diabetes under the care of pediatric endocrinologists in the United States meeting targets for HbA1c, blood pressure (BP), BMI, and lipids.Data were evaluated for 13,316 participants in the T1D Exchange clinic registry younger than 20 years old with type 1 diabetes for ≥1 year.American Diabetes Association HbA1c targets of <8.5% for those younger than 6 years, <8.0% for those 6 to younger than 13 years old, and <7.5% for those 13 to younger than 20 years old were met by 64, 43, and 21% of participants, respectively. The majority met targets for BP and lipids, and two-thirds met the BMI goal of <85th percentile.Most children with type 1 diabetes have HbA1c values above target levels. Achieving American Diabetes Association goals remains a significant challenge for the majority of youth in the T1D Exchange registry.
The role of the renin-angiotensin system in mediation of adrenal catecholamine secretion in the cat induced by intrarenal beta-adrenergic stimulation.
Authors: M M Krausz, G Feuerstein, N Feuerstein, Y Gutman
Journal: Circulation Research (1980)

Isoproterenol infusion (0.1 microgram/kg per min) into the renal artery of the cat induced an increase in plasma renin concentration (PRC) from 14.3 +/- 5.7 (mean +/- SE) ng angiotensin I/ml per hr to 56.8 +/- 7.7 after 70 minutes (P &lt; 0.05) and an increase in catecholamine secretion rate from 38.7 +/- 6.0 ng/kg per 10 min to 180.0 +/- 40.0 after 70 minutes (P &lt; 0.001). Intravenous infusion of the same dose of isoproterenol had no significant effect on adrenomedullary catecholamine secretion rate. Isoproterenol induced preferential norepinephrine release: the ratio of norepinephrine to epinephrine secretion changed from 11.5:23.7 during the control period to 130.0:40.1 70 minutes after the start of isoproterenol administration. Intrarenal infusion of propranolol (3.0 mg/kg per min) inhibited renal renin release and adrenal catecholamine secretion in response to intrarenal isoproterenol. Intravenous infusion (0.4 microgram/kg per min) of an angiotensin II antagonist [Sar1, Ileu8]angiotensin II abolished the catecholamine response to intrarenal isoproterenol infusion. It is suggested that intrarenal isoproterenol infusion stimulates renal renin release and angiotensin production which, in turn, stimulates a preferential secretion of adrenomedullary norepinephrine.
Reduction in mortality after inappropriate early discharge from intensive care unit: logistic regression triage
Authors: K. Daly
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To develop a predictive model to triage patients for discharge from intensive care units to reduce mortality after discharge. <b>Design:</b> Logistic regression analyses and modelling of data from patients who were discharged from intensive care units. <b>Setting:</b> Guy9s hospital intensive care unit and 19 other UK intensive care units from 1989 to 1998. <b>Participants:</b> 5475 patients for the development of the model and 8449 for validation. <b>Main outcome measures:</b> Mortality after discharge and power of triage model. <b>Results:</b> Mortality after discharge from intensive care was up to 12.4%. The triage model identified patients at risk from death on the ward with a sensitivity of 65.5% and specificity of 87.6%, and an area under the receiver operating curve of 0.86. Variables in the model were age, end stage disease, length of stay in unit, cardiothoracic surgery, and physiology. In the validation dataset the 34% of the patients identified as at risk had a discharge mortality of 25% compared with a 4% mortality among those not at risk. <b>Conclusions:</b> The discharge mortality of at risk patients may be reduced by 39% if they remain in intensive care units for another 48 hours. The discharge triage model to identify patients at risk from too early and inappropriate discharge from intensive care may help doctors to make the difficult clinical decision of whom to discharge to make room for a patient requiring urgent admission to the unit. If confirmed, this study has implications on the provision of resources. <h3>What is already known on this topic</h3> In the United Kingdom, the mortality of patients who die on the ward after discharge from intensive care is unacceptably high (9% to 27%) Indirect evidence has shown that this is due to too early and inappropriate discharge from intensive care that has increased over the past 10 years <h3>What this study adds</h3> A triage model identifies patients at risk from inappropriate discharge from intensive care Mortality after discharge from intensive care may be reduced by 39% if these patients were to stay in intensive care for another 48 hours An estimated 16% more beds are required if mortality after discharge from intensive care is to be reduced
Detecting sequence polymorphisms associated with meiotic recombination hotspots in the human genome
Authors: Jie Zheng, Pavel P Khil, R Daniel Camerini-Otero, Teresa M Przytycka
Journal: Genome biology (2010)

Meiotic recombination events tend to cluster into narrow spans of a few kilobases long, called recombination hotspots. Such hotspots are not conserved between human and chimpanzee and vary between different human ethnic groups. At the same time, recombination hotspots are heritable. Previous studies showed instances where differences in recombination rate could be associated with sequence polymorphisms. In this work we developed a novel computational approach, LDsplit, to perform a large-scale association study of recombination hotspots with genetic polymorphisms. LDsplit was able to correctly predict the association between the FG11 SNP and the DNA2 hotspot observed by sperm typing. Extensive simulation demonstrated the accuracy of LDsplit under various conditions. Applying LDsplit to human chromosome 6, we found that for a significant fraction of hotspots, there is an association between variations in intensity of historical recombination and sequence polymorphisms. From flanking regions of the SNPs output by LDsplit we identified a conserved 11-mer motif GGNGGNAGGGG, whose complement partially matches 13-mer CCNCCNTNNCCNC, a critical motif for the regulation of recombination hotspots. Our result suggests that computational approaches based on historical recombination events are likely to be more powerful than previously anticipated. The putative associations we identified may be a promising step toward uncovering the mechanisms of recombination hotspots.
A multicenter evaluation of genotypic methods for the epidemiologic typing of Legionella pneumophila serogroup 1: results of a pan-European study
Authors: Norman K. Fry, Stella Alexiou-Daniel, Jette M. Bangsborg, Sverker Bernander, Maddalena Castellani Pastoris, Jerome Etienne, Benita Forsblom, Valeria Gaia, Jörgen H. Helbig, Diane Lindsay, P. Christian Löck, Carmen Pelaz, SØren A. Uldum, Timothy G. Harrison
Journal: Clinical Microbiology and Infection (1999)