tbuckley/cabot-search huggingface dataset:
Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients
Authors: Samuel Z. Goldhaber, Alain Leizorovicz, Ajay K. Kakkar, Sylvia K. Haas, Geno Merli, Robert M. Knabb, Jeffrey I. Weitz
Journal: New England Journal of Medicine (2011)

The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin.In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated.A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome--2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P=0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P=0.04).In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.).
<i>CCR</i> 20th Anniversary Commentary: Preclinical Study of Proteasome Inhibitor Bortezomib in Head and Neck Cancer
Authors: Clint T. Allen, Barbara Conley, John B. Sunwoo, Carter Van Waes
Journal: Clinical Cancer Research (2015)

Abstract In a study published in the May 1, 2001, issue of Clinical Cancer Research, Sunwoo and colleagues provided evidence for proteasome inhibition of NF-κB and tumorigenesis, supporting early-phase clinical trials in solid malignancies of the upper aerodigestive tract. Subsequent clinical studies uncovered a dichotomy of responses in patients with hematopoietic and solid malignancies, and the mechanisms of resistance. Clin Cancer Res; 21(5); 942–3. ©2015 AACR. See related article by Sunwoo et al., Clin Cancer Res 2001;7(5) May 2001;1419–28
Involvement of cell surface heparin sulfate in the binding of lipoprotein lipase to cultured bovine endothelial cells.
Authors: K Shimada, P J Gill, J E Silbert, W H Douglas, B L Fanburg
Journal: Journal of Clinical Investigation (1981)

It has been postulated that lipoprotein lipase, an enzyme important in the uptake of fatty acids into tissues, is bound to the vascular endothelial cell surface and that this binding occurs through attachment to heparinlike glycosaminoglycans. Furthermore, it is thought that heparin releases the enzyme from its attachment to the endothelium into the circulation. These hypotheses have never been tested directly in cell systems in vitro. In the present study we have directly evaluated the interaction of lipoprotein lipase, purified from bovine skim milk with monolayer cultures of endothelial cells, isolated from bovine pulmonary artery. Endothelial cells in primary culture had no intrinsic lipoprotein lipase activity but were able to bind lipoprotein lipase quantitatively. The binding reached equilibrium and was saturable at 0.24 nmol of lipoprotein lipase/mg of cell protein. The concentration of lipoprotein lipase at half-maximal binding was 0.52 microM. Bound lipoprotein lipase could be detached from cultured cells by increasing concentrations of heparin, and at and above 0.6 microgram/ml of heparin, 90% of the cell-bound lipoprotein lipase activity was released. Heparan sulfate and dermatan sulfate released the enzyme to a lesser extent and chondroitin sulfate caused little, if any, release of lipoprotein lipase. The release of lipoprotein lipase with heparin was not associated with a release of [3S]glycosaminoglycans from 35S-prelabeled cells. Reductions of lipoprotein lipase binding to endothelial cells and of cell surface-associated [3S]glycosaminoglycans in 35S-prelabeled cells occurred in parallel both when cells were pretreated with crude Flavobacterium heparinum enzyme before lipoprotein lipase binding and when cells were treated with this enzyme after lipoprotein lipase binding. The removal of heparan sulfate from the cell surface by purified heparinase totally inhibited the binding of lipoprotein lipase by endothelial cells, but the removal of chondroitin sulfate by chondroitin ABC lyase had no effect on this binding. These results provide direct evidence for lipoprotein lipase attachment to endothelial cells through heparan sulfate on the cell surface, and provide evidence for the release of lipoprotein lipase by heparin through a detachment from this binding site.
Sustained Elevation of Serum Cortisol Level Causes Sensitization of Coronary Vasoconstricting Responses in Pigs In Vivo
Authors: Takatoshi Hizume, Keiko Morikawa, Aya Takaki, Kohtaro Abe, Kenji Sunagawa, Mutsuki Amano, Kozo Kaibuchi, Chiharu Kubo, Hiroaki Shimokawa
Journal: Circulation Research (2006)

Vasospastic angina is induced by stress, for which cortisol secreted by activated hypothalamic/pituitary/adrenal axis may play an important role. However, direct evidence for this notion is still lacking. In this study, we examined whether sustained elevation of serum cortisol level sensitizes coronary vasoconstricting responses in pigs in vivo and, if so, whether Rho-kinase, which we found is a key molecule of coronary vasospasm, is involved. Oral administration of cortisol (20 mg/kg per day) increased its serum level to that seen in restraint stress in pigs. Thus, we examined coronary vasomotor responses in the following 4 groups: (1) control (without cortisol); (2) cortisol (20 mg/kg per day, p.o.) for 9 days; (3) cortisol plus RU38486 (a glucocorticoids receptor antagonist, 10 mg/kg per day, p.o.) for 9 days; and (4) cortisol for 9 days followed by 6-week withdrawal. Coronary angiography showed that intracoronary serotonin caused coronary hyperconstriction and reduction in coronary blood flow associated with ischemic ECG changes (coronary vasospasm) in only the cortisol group. All of these responses were abolished by hydroxyfasudil, a specific Rho-kinase inhibitor, in vivo. Organ chamber experiments demonstrated that serotonin concentration-dependently caused hypercontractions of coronary vascular smooth muscle associated with Rho-kinase activation (as evidenced by the enhanced phosphorylation of myosin binding subunit, a substrate of Rho-kinase) in only the cortisol group. All of these responses were again inhibited by hydroxyfasudil in vitro. These results indicate that sustained elevation of serum cortisol level sensitizes coronary vasoconstricting responses through Rho-kinase activation, suggesting the link between stress and coronary vasospasm.
Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease
Authors: Mark I Rees, Kirsten Harvey, Brian R Pearce, Seo-Kyung Chung, Ian C Duguid, Philip Thomas, Sarah Beatty, Gail E Graham, Linlea Armstrong, Rita Shiang, Kim J Abbott, Sameer M Zuberi, John B P Stephenson, Michael J Owen, Marina A J Tijssen, Arn M J M van den Maagdenberg, Trevor G Smart, Stéphane Supplisson, Robert J Harvey
Journal: Nature Genetics (2006)
Long-Term Results of Autologous Hematopoietic Stem-Cell Transplantation After High-Dose <sup>90</sup>Y-Ibritumomab Tiuxetan for Patients With Poor-Risk Non-Hodgkin Lymphoma Not Eligible for High-Dose BEAM
Authors: Liliana Devizzi, Anna Guidetti, Ettore Seregni, Roberto Passera, Marco Maccauro, Michele Magni, Adele Testi, Massimo Di Nicola, Corrado Tarella, Paola Matteucci, Simonetta Viviani, Marco Ruella, Carmelo Carlo-Stella, Carlo Chiesa, Maria Cristina Cox, Emilio Bombardieri, Alessandro M. Gianni
Journal: Journal of Clinical Oncology (2013)

the almost universal negative perceptions of chemotherapy.The impact of direct-to-consumer advertising is unknown, 4 but patients would presumably be attracted by the concept of supportive care options (such as growth factors) that promise reduced toxicity, even if the evidence does not support this.Finally, the strong social media presence of pharmaceutical companies 5 highlights the emerging role of new Web-based technologies as a marketing strategy that targets patients and clinicians.Our data strongly suggest that medical oncologists in Australia are not necessarily motivated by financial gain to the extent that the treatment received by patients is affected.The extent to which our results can be generalized is unknown, but we would argue that the many factors affecting therapy received do each need to be considered before concluding any direct link between financial incentives and changed clinical practice.Ultimately, although oncologists need to be cognizant of the rising costs of health care, it is critical that we as clinicians are allowed to provide the best possible care for our patients and are not made to feel guilty for prescribing expensive therapies when these are the best option.
Using Protein Expressions to Predict Survival in Clear Cell Renal Carcinoma
Authors: Hyung L. Kim, David Seligson, Xueli Liu, Nicolette Janzen, Matthew H. T. Bui, Hong Yu, Tao Shi, Robert A. Figlin, Steve Horvath, Arie S. Belldegrun
Journal: Clinical Cancer Research (2004)

Abstract Purpose: An accurate system for predicting survival for patients with solid tumors will allow for better patient selection for both established and novel therapies. We propose a staging system for clear cell variants of renal cell carcinoma (RCC) that includes molecular predictors and standard clinical predictors such as tumor-node-metastasis (TNM) stage, histological grade, and performance status (PS). Experimental Design: A custom tissue array was constructed using clear cell RCC from 318 patients, representing all stages of localized and metastatic RCC, and immunohistochemically stained for molecular markers Ki67, p53, gelsolin, CA9, CA12, PTEN, EpCAM, and vimentin. We present a strategy for evaluating individual candidate markers for prognostic information and integrating informative markers into a multivariate prognostic system. Results: The overall median follow-up and the median follow-up for surviving patients were 28 and 55 months, respectively. A prognostic model based primarily on molecular markers included metastasis status, p53, CA9, gelsolin, and vimentin as predictors and had high discriminatory power: its statistically validated concordance index (C-index) was found to be 0.75. A prognostic model based on a combination of clinical and molecular predictors included metastasis status, T stage, Eastern Cooperative Oncology Group PS, p53, CA9, and vimentin as predictors and had a C-index of 0.79, which was significantly higher (P &amp;lt; 0.05) than that of prognostic models based on grade alone (C = 0.65), TNM stage alone (C = 0.73), or the University of California Los Angeles integrated staging system (C = 0.76). Conclusions: Protein expressions obtained using widely available technology can complement standard clinical predictors such as TNM stage, histological grade, and PS.
Error, Bias, and Long-Branch Attraction in Data for Two Chloroplast Photosystem Genes in Seed Plants
Authors: M. J. Sanderson, M. F. Wojciechowski, J.-M. Hu, T. Sher Khan, S. G. Brady
Journal: Molecular Biology and Evolution (2000)

Sequences of two chloroplast photosystem genes, psaA and psbB, together comprising about 3,500 bp, were obtained for all five major groups of extant seed plants and several outgroups among other vascular plants. Strongly supported, but significantly conflicting, phylogenetic signals were obtained in parsimony analyses from partitions of the data into first and second codon positions versus third positions. In the former, both genes agreed on a monophyletic gymnosperms, with Gnetales closely related to certain conifers. In the latter, Gnetales are inferred to be the sister group of all other seed plants, with gymnosperms paraphyletic. None of the data supported the modern “anthophyte hypothesis,” which places Gnetales as the sister group of flowering plants. A series of simulation studies were undertaken to examine the error rate for parsimony inference. Three kinds of errors were examined: random error, systematic bias (both properties of finite data sets), and statistical inconsistency owing to long-branch attraction (an asymptotic property). Parsimony reconstructions were extremely biased for third-position data for psbB. Regardless of the true underlying tree, a tree in which Gnetales are sister to all other seed plants was likely to be reconstructed for these data. None of the combinations of genes or partitions permits the anthophyte tree to be reconstructed with high probability. Simulations of progressively larger data sets indicate the existence of long-branch attraction (statistical inconsistency) for third-position psbB data if either the anthophyte tree or the gymnosperm tree is correct. This is also true for the anthophyte tree using either psaA third positions or psbB first and second positions. A factor contributing to bias and inconsistency is extremely short branches at the base of the seed plant radiation, coupled with extremely high rates in Gnetales and nonseed plant outgroups.
Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS)
Authors: D D Gladman, C T Schentag, B D M Tom, V Chandran, J Brockbank, C Rosen, V T Farewell
Journal: Annals of the Rheumatic Diseases (2008)

Objective: To develop and validate a psoriatic arthritis (PsA) screening questionnaire: the Toronto Psoriatic Arthritis Screen (ToPAS). Methods: The ToPAS was developed through review of items seen in patients with PsA and evaluation by patients with PsA and patients with other rheumatological conditions, and was administered to consecutive consenting patients attending five clinics: PsA, psoriasis, general dermatology, general rheumatology (excluding PsA patients) and family medicine. All patients were assessed by a rheumatologist according to a standard protocol. A three-step analysis strategy was adopted: a stepwise logistic regression to identify the questions most important in discriminating between those with and without PsA; a logistic model was fitted to three clinically relevant domains for PsA: skin, joints and nails; and a simpler weighting of each of the domains used in step 2. Receiver operating characteristic (ROC) curves were obtained based on these various models. Results: In all, there were 134 patients from the PsA clinic, 123 with psoriasis, 118 from dermatology, 135 from rheumatology and 178 from family medicine. A simplified discriminatory score based on the skin, joint and nail domains gave results comparable to other methods with an observed overall sensitivity and specificity, based on a single cut point, of 86.8% and 93.1%. When the patients with PsA were compared with each of the other four patient groups individually, the sensitivity and specificity of the ToPAS were: psoriasis 89.1%, 86.3%; dermatology 91.9%, 95.2%; rheumatology 92.6%, 85.7%; and family medicine 90.4%, 100%. Conclusion: Our simplified index is very good at classifying those who are not diagnosed with PsA and those who are diagnosed with PsA.
Blood Glucose Awareness Training Delivered Over the Internet
Authors: Daniel Cox, Lee Ritterband, Joshua Magee, William Clarke, Linda Gonder-Frederick
Journal: Diabetes Care (2008)

Blood glucose awareness training (BGAT), a psycho-educational intervention, trains individuals with type 1 diabetes to 1) detect/interpret internal cues to better detect extreme blood glucose levels, e.g., neurogenic and neuroglycopenic symptoms; and 2) interpret external cues to detect current and anticipate future extreme blood glucose levels, e.g., insulin timing/dose and recent self-monitoring of blood glucose results. Although outcome studies using BGAT are significant, limitations include the requirement of eight weekly meetings and limited professionals trained to deliver BGAT.Due to the limitations mentioned above, BGAT was converted for web-based delivery. The internet allows BGAT delivery to be dynamic, engaging, convenient, and personalized. Efficacy was evaluated using a 2 (BGAThome, n = 20, vs. control, n = 20) x 2 (pre/post) design.BGAThome was judged as useful and easy to use, was completed by 94% of the participants, and resulted in significant clinical improvements (P < 0.05).The internet may be an efficient and effective means of delivering diabetes interventions like BGAT.
Rheumatic Heart Disease Complicating Pregnancy
Authors: M. K. O'Driscoll, A. P. Barry, M. I. Drury
Journal: BMJ (1957)

A clinical study of rheumatic heart disease complicating pregnancy was begun at the National Maternity Hos- pital on January 1, 1948.During the first four year,s 250 cases were treated, and these have been analysed (Drury et al., 1954).In that series there was no indirect case selection, and the patients were of an age and parity rarely seen elsewhere.During the subsequent four years 289 similar cases have been observed.These are now presented to show the results that have been attained by conservative management.This series is comparable to the previous one except that, in reference to the mothers, it concludes at the end of the puerperium, a period of six weeks following delivery.It is intended that a prolonged follow-up of all these women will be presented later.During the four-year period some of the women had more than one delivery; each pregnancy is considered as a separate case. Analysis of 289 Cases
Biochemical and virological outcome of patients with chronic hepatitis C treated with interferon alfa-2b for 6 or 12 months: A 4-year follow-up of 211 patients
Authors: E K Manesis, C Papaioannou, A Gioustozi, G Kafiri, J Koskinas, S J Hadziyannis
Journal: Hepatology (1997)

To compare two interferon (IFN) schedules for the treatment of chronic hepatitis C, we followed 211 patients who received 3 million units IFN-alpha2b thrice weekly for either 6 months (group 1; 85 patients) or 12 months (group 2; 126 patients), with a median follow-up of 3.4 (0.1-8.4) and 4.2 (0.7-8.7) years, respectively. The biochemical and virological responses at the end of treatment were 34.1% and 16.5% versus 62.7% and 41.2% for the 6- and the 12-month regimens, respectively. Late biochemical responses (after the third month of treatment) occurred in 30.6% of responding patients, and they were not particularly associated with an adverse long-term treatment outcome. In a multivariate analysis, patients with a primary response were significantly more frequently infected with a non-1b HCV genotype (relative risk [RR]: 14.4), had been treated for 12 months (RR: 6.0), and had an early stage of liver fibrosis (RR: 5.2). Baseline serum HCV-RNA and ferritin levels also bore a significant, though weaker, association with a primary response. Using a set of pretreatment variables in a model of discriminant analysis, we could correctly predict the long-term virological outcome in 86.6% of the individual cases. At the end of follow-up, a biochemical and virological sustained response was observed in 14.1% and 11.8% versus 40.5% and 31% of groups 1 and 2, respectively. Significant predictors of a virological sustained response were a virological primary response (RR: 41.2) and the pretreatment level of serum HCV-RNA (RR: 10.3 per each 10(6)-Eq/mL decrease). Patients with a "good treatment profile," including an early stage of liver fibrosis, a non-1b genotype and serum HCV-RNA <0.35 x 10(6) Eq/mL, had a 66.7% rate of observed virological SR, compared with a zero response for those with the opposite, a "bad treatment profile." We conclude that a 12-month IFN treatment, along with a non-1b genotype and the absence of advanced stage of fibrosis, are the main determinants for the induction of a virological primary response in chronic hepatitis C. Such response, along with a low pretreatment serum HCV-RNA level, are the main predictors for a 4-year virological response to IFN.
A 20-Year Longitudinal Observational Study of Somatic Antidepressant Treatment Effectiveness
Authors: Andrew C. Leon, David A. Solomon, Timothy I. Mueller, Jean Endicott, John P. Rice, Jack D. Maser, William Coryell, Martin B. Keller
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This observational study examined the effectiveness of somatic antidepressant treatments as administered in the community. METHOD: The study group consisted of 285 subjects with an intake diagnosis of major depressive disorder who had entered the National Institute of Mental Health Collaborative Depression Study as early as 1978, had at least one additional affective episode, and had been followed for up to 20 years, as recently as 1999. The characteristics that distinguished subjects receiving various levels of somatic antidepressant treatment were accounted for in what was called a propensity for treatment intensity model. The effectiveness of somatic antidepressant treatment during major affective episodes was then examined. RESULTS: Those who received higher levels of antidepressant treatment tended to have more prior episodes, more severe depressive symptoms, and more intensive somatic therapy during prior episodes and prior well intervals than those who received lower levels. Treatment effectiveness analyses that were stratified by propensity for treatment intensity demonstrated that those who received higher levels of antidepressant treatment were significantly more likely to recover from affective episodes. In contrast, those treated with lower levels were no more likely to recover than those who did not receive somatic treatment. CONCLUSIONS: Despite the indications of more severe depressive illness, those who received higher levels of somatic antidepressant treatment were more likely to recover from recurrent affective episodes. Results from this observational study extend the generalizability of reports from randomized clinical trials of antidepressants to a wider, more representative group of individuals who suffer from major depression.
Cardiovascular Collagenosis with Parietal Endocardial Thrombosis
Authors: B. J. P. BECKER, C. B. CHATGIDAKIS, B. VAN LINGEN
Journal: Circulation (1953)

Forty cases of endocardial thrombosis of the heart were selected for pathologic study from a total of 9,500 autopsies performed during 1936 to 1951. Widespread focal involvement of the connective tissue throughout the body and particularly in the heart was demonstrated. Although the histopathologic features were similar to those found in the "diffuse collagen diseases" they did not show the characteristic lesions of rheumatic fever, periarteritis nodosa, lupus erythematosus or diffuse scleroderma. The clinical presentation of a rapidly progressive heart failure, together with the pathologic findings, were sufficiently distinctive to consider this condition as a cardiovascular collagenosis with parietal thrombosis. A similar condition has been described under a variety of names and would appear to constitute a large proportion of cases of so-called "idiopathic hypertrophy" or "myocarditis" of the heart.