tbuckley/cabot-search huggingface dataset:
Intrapleural Streptokinase for Empyema and Complicated Parapneumonic Effusions
Authors: Andreas H. Diacon, Johan Theron, Macé M. Schuurmans, Bernard W. Van de Wal, Chris T. Bolliger
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We conducted a single-center, randomized, placebo-controlled trial to determine whether streptokinase instillations adjunctive to chest tube drainage reduce the need for surgery and improve outcome in patients with pleural empyema. Fifty-three patients (frank pus aspirated, 81%; microbiological agent cultured, 62%; mean effusion pH, 6.6 +/- 0.4) received antibiotic treatment, chest tube drainage, and once-daily pleural rinses with either normal saline or normal saline with streptokinase (250,000 IU). Nine patients were excluded for various reasons before pleural rinses were started. Streptokinase (n = 22) was instilled over 4.5 +/- 2 days and saline (n = 22) was instilled over 3 +/- 1.3 days. One patient in each group died during treatment. Clinical treatment success and need for referral to surgery were the main outcome measures. No difference was observed after 3 days. After 7 days, streptokinase-treated patients had a higher clinical success rate (82 vs. 48%, p = 0.01) and fewer referrals for surgery (45 vs. 9%, p = 0.02). No significant radiologic or functional differences were observed between groups during follow-up over 6 months. We conclude that intrapleural streptokinase adjunctive to chest tube drainage reduces the need for surgery and improves the clinical treatment success in patients with pleural empyema.
Breast or bottle.
Authors: J Gray
Journal: BMJ (1979)

patients continue to exhibit an unfavourable cervix resistant to induction post term and most of these benefit from local prostaglandins.With careful adjustment, the highly sophisticated cardiotocographic monitors avail- able today allow very satisfactory recordings to be made.Perhaps in our critical age induction with a PGE2 pessary should constitute the only permissible form of "stress test."After all, if a potentially com- promised fetus shows distress at this early stage, then expedited delivery by the most appropriate route would obviously be in the best interests of the fetus.In the future, different doses of PGE2pessaries will be available, depending on the requirements of the individual patient.It may be that 1 mg, 3 mg, and 5 mg pessaries will prove necessary, and perhaps when the drug companies concerned are more interested in the commercial aspect of their production this will be possible.Each pessary costs approximately £6, but surely this, or S14, is not a large sum when compared with the potential benefits gained, especially if caesarean section and its attendant price are avoided, as our reported series showed possible.Given the choice, patients prefer this method of "non- invasive" induction, and if they had to most would be willing to pay for it.At present, in many centres in America, the caesarean section rate is much higher than that in Great Britain.There are many reasons for this, but quite definitely, if the United States Food and Drug Administration were to recognise the tremendous potential and advantages of locally administered prostaglandins, then prolonged inductions ending in failure and inevitable caesarean section could be avoided in the USA too.This would be especially important ina country where the maxim "Once a section, always a section" is very widely applied.
Recent Advances in the Prevention and Management of Intradialytic Hypotension
Authors: Biff F. Palmer, William L. Henrich
Journal: Journal of the American Society of Nephrology (2008)

Intradialytic hypotension continues to play a significant role in the morbidity and in some cases the mortality associated with maintenance hemodialysis. Greater precision in the determination of dry weight using bioimpedance technology and biofeedback systems designed to prevent rapid fluctuations in blood volume have recently been shown to decrease the frequency of this complication. Pharmacologic strategies designed to maintain peripheral vascular resistance in patients with insufficient release of endogenous vasoconstrictors continue to be explored. The sudden development of intradialytic hypotension may respond to specific antagonists to hypotensive mediators.
Jak1 deficiency leads to enhanced Abelson-induced B-cell tumor formation
Authors: Veronika Sexl, Boris Kovacic, Roland Piekorz, Richard Moriggl, Dagmar Stoiber, Angelika Hoffmeyer, Rita Liebminger, Oliver Kudlacek, Eva Weisz, Kristen Rothammer, James N. Ihle
Journal: Blood (2003)
Supervised Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac Peripheral Artery Disease
Authors: Timothy P. Murphy, Donald E. Cutlip, Judith G. Regensteiner, Emile R. Mohler, David J. Cohen, Matthew R. Reynolds, Joseph M. Massaro, Beth A. Lewis, Joselyn Cerezo, Niki C. Oldenburg, Claudia C. Thum, Suzanne Goldberg, Michael R. Jaff, Michael W. Steffes, Anthony J. Comerota, Jonathan Ehrman, Diane Treat-Jacobson, M. Eileen Walsh, Tracie Collins, Dalynn T. Badenhop, Ulf Bronas, Alan T. Hirsch
Journal: Circulation (2011)

Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST).We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P<0.001 for the comparison of SE versus OMC, P=0.02 for ST versus OMC, and P=0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus -6±109 steps per hour), but these differences were not statistically significant.SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study.URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1. Unique identifier: NCT00132743.
Phase II and Pharmacokinetic Study of Ecteinascidin 743 in Patients With Progressive Sarcomas of Soft Tissues Refractory to Chemotherapy
Authors: R. Garcia-Carbonero, J.G. Supko, J. Manola, M.V. Seiden, D. Harmon, D.P. Ryan, M.T. Quigley, P. Merriam, J. Canniff, G. Goss, U. Matulonis, R.G. Maki, T. Lopez, T.A. Puchalski, M.A. Sancho, J. Gomez, C. Guzman, J. Jimeno, G.D. Demetri
Journal: Journal of Clinical Oncology (2004)

Purpose To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. Patients and Methods Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 μg/m 2 every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. Results Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean ± standard deviation), 1.04 ± 0.48 ng/mL and 35.6 ± 16.2 L/h/m 2 , respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. Conclusion ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.
The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation
Authors: Abanti Chaudhuri, Mikki Ozawa, Matthew J. Everly, Robert Ettenger, Vikas Dharnidharka, Mark Benfield, Robert Mathias, Anthony Portale, Ruth McDonald, William Harmon, David Kershaw, V. Matti Vehaskari, Elaine Kamil, H. Jorge Baluarte, Bradley Warady, Li Li, Tara K. Sigdel, Szu-chuan Hsieh, Hong Dai, Maarten Naesens, Janie Waskerwitz, Oscar Salvatierra, Paul I. Terasaki, Minnie M. Sarwal
Journal: Journal of the American Society of Nephrology (2013)

The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.
Locoregional Control of Clinically Diagnosed Multifocal or Multicentric Breast Cancer After Neoadjuvant Chemotherapy and Locoregional Therapy
Authors: Julia L. Oh, Mark J. Dryden, Wendy A. Woodward, Tse-Kuan Yu, Welela Tereffe, Eric A. Strom, George H. Perkins, Lavinia Middleton, Kelly K. Hunt, Sharon H. Giordano, Mary Jane Oswald, Delora Domain, Thomas A. Buchholz
Journal: Journal of Clinical Oncology (2006)

The purpose was to assess whether patients with clinical multifocal or multicentric (MFMC) breast cancer determined by mammogram, ultrasound, or physical examination have inferior outcome compared with patients with clinical unicentric lesions.We retrospectively analyzed 706 consecutive patients with stages I-III breast cancer treated at the M.D. Anderson Cancer Center (Houston, TX) from 1976 to 2003 who received neoadjuvant anthracycline-based chemotherapy followed by breast conservation therapy (BCT), mastectomy alone, or mastectomy plus postmastectomy radiation therapy.The mean follow-up was 66 months. At presentation, 97 of 706 patients had clinically MFMC disease (13.7%). The 5-year rate of locoregional failure was 10% for unicentric disease compared with 7% for MFMC disease (P = .78). Subset analyses of patients by treatment groups confirmed no statistical difference in locoregional control regardless of the type of locoregional treatment. Among patients with multifocal disease treated with BCT, there were no in-breast recurrences and one supraclavicular recurrence. Five-year disease-free survival and overall survival was equivalent between patients with MFMC and unicentric breast cancers.Patients with clinical MFMC breast cancer at the time of diagnosis treated with neoadjuvant chemotherapy followed by locoregional therapy have similar 5-year rates of locoregional control, disease-free survival, and overall survival as those with unicentric disease. Clinically detected MFMC disease did not predict for inferior outcome.
Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study
Authors: D. Schadendorf, A. Hauschild, S. Ugurel, A. Thoelke, F. Egberts, M. Kreissig, R. Linse, U. Trefzer, T. Vogt, W. Tilgen, P. Mohr, C. Garbe
Journal: Annals of Oncology (2006)
Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies
Authors: Raoul Tibes, Ruben A Mesa
Journal: Journal of Hematology & Oncology (2014)

Treatment of myelofibrosis (MF), a BCR-ABL–negative myeloproliferative neoplasm, is challenging. The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. The remaining patients are treated with palliative therapies to manage MF-related anemia and splenomegaly. Identification of a mutation in the Janus kinase 2 (JAK2) gene (JAK2 V617F) in more than half of all patients with MF has prompted the discovery and clinical development of inhibitors that target JAK2. Although treatment with JAK2 inhibitors has been shown to improve symptom response and quality of life in patients with MF, these drugs do not alter the underlying disease; therefore, novel therapies are needed. The hedgehog (Hh) signaling pathway has been shown to play a role in normal hematopoiesis and in the tumorigenesis of hematologic malignancies. Moreover, inhibitors of the Hh pathway have been shown to inhibit growth and self-renewal capacity in preclinical models of MF. In a mouse model of MF, combined inhibition of the Hh and JAK pathways reduced JAK2 mutant allele burden, reduced bone marrow fibrosis, and reduced white blood cell and platelet counts. Preliminary clinical data also suggest that inhibition of the Hh pathway, alone or in combination with JAK2 inhibition, may enable disease modification in patients with MF. Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification.
Heat Shock Protein 20 Interacting With Phosphorylated Akt Reduces Doxorubicin-Triggered Oxidative Stress and Cardiotoxicity
Authors: Guo-Chang Fan, Xiaoyang Zhou, Xiaohong Wang, Guojie Song, Jiang Qian, Persoulla Nicolaou, Guoli Chen, Xiaoping Ren, Evangelia G. Kranias
Journal: Circulation Research (2008)

Doxorubicin (DOX) is a widely used antitumor drug, but its application is limited because of its cardiotoxic side effects. Heat shock protein (Hsp)20 has been recently shown to protect cardiomyocytes against apoptosis, induced by ischemia/reperfusion injury or by prolonged β-agonist stimulation. However, it is not clear whether Hsp20 would exert similar protective effects against DOX-induced cardiac injury. Actually, DOX treatment was associated with downregulation of Hsp20 in the heart. To elucidate the role of Hsp20 in DOX-triggered cardiac toxicity, Hsp20 was first overexpressed ex vivo by adenovirus-mediated gene delivery. Increased Hsp20 levels conferred higher resistance to DOX-induced cell death, compared to green fluorescent protein control. Furthermore, cardiac-specific overexpression of Hsp20 in vivo significantly ameliorated acute DOX-triggered cardiomyocyte apoptosis and animal mortality. Hsp20 transgenic mice also showed improved cardiac function and prolonged survival after chronic administration of DOX. The mechanisms underlying these beneficial effects were associated with preserved Akt phosphorylation/activity and attenuation of DOX-induced oxidative stress. Coimmunoprecipitation studies revealed an interaction between Hsp20 and phosphorylated Akt. Accordingly, BAD phosphorylation was preserved, and cleaved caspase-3 was decreased in DOX-treated Hsp20 transgenic hearts, consistent with the antiapoptotic effects of Hsp20. Parallel ex vivo experiments showed that either infection with a dominant-negative Akt adenovirus or preincubation of cardiomyocytes with the phosphatidylinositol 3-kinase inhibitors significantly attenuated the protective effects of Hsp20. Taken together, our findings indicate that overexpression of Hsp20 inhibits DOX-triggered cardiac injury, and these beneficial effects appear to be dependent on Akt activation. Thus, Hsp20 may constitute a new therapeutic target in ameliorating the cardiotoxic effects of DOX treatment in cancer patients.
Microbial Modulation of Energy Availability in the Colon Regulates Intestinal Transit
Authors: Anita Wichmann, Ava Allahyar, Thomas U. Greiner, Hubert Plovier, Gunnel Östergren Lundén, Thomas Larsson, Daniel J. Drucker, Nathalie M. Delzenne, Patrice D. Cani, Fredrik Bäckhed
Journal: Cell Host & Microbe (2013)
Randomized Comparison of Group Versus Individual Genetic Education and Counseling for Familial Breast and/or Ovarian Cancer
Authors: Kathleen A. Calzone, Sheila A. Prindiville, Oxana Jourkiv, Jean Jenkins, Maria DeCarvalho, Dawn B. Wallerstedt, David J. Liewehr, Seth M. Steinberg, Peter W. Soballe, Stan Lipkowitz, Pamela Klein, Ilan R. Kirsch
Journal: Journal of Clinical Oncology (2005)

Purpose An efficient approach to education and counseling before BRCA1 and BRCA2 mutation testing is necessary for effective utilization of testing in the community. Education and counseling, when delivered individually, are limited by a shortage of trained health care providers as well as by financial and time constraints. The purpose of this study was to determine whether pretest education and counseling for breast cancer genetics in a group setting is equivalent to that provided on an individual basis. Patients and Methods One hundred forty-two patients at high risk for harboring a BRCA mutation were randomly assigned to group or individual education and counseling sessions. Group education was followed by brief individual counseling. Knowledge and Impact of Events Scales (IES) were administered at baseline and after education and counseling and at 1 week and 3, 6, and 12 months. Satisfaction with education and counseling was measured at completion of the session. Preferred method of education and counseling was solicited at 3 months. Results There was no difference in knowledge or IES scores between groups. When stratified by genetic test results, knowledge scores showed no difference. Regardless of group, post-test IES scores in patients with positive results were higher than patients with negative or uninformative results but returned to baseline by 12 months. Participants were equally satisfied with either method they were assigned. Significantly more time was spent per patient in individual sessions (1.25 hours) than in group education (0.74 hours). Conclusion Our data suggest that group education and counseling may confer similar benefits compared with traditional individual sessions. Additional investigation of this approach in larger numbers of patients is warranted.
A molecular comparison of microbial communities in bronchiectasis and cystic fibrosis
Authors: Rachael M. Duff, Nicholas J. Simmonds, Jane C. Davies, Robert Wilson, Eric W. Alton, Panagiotis Pantelidis, Michael J. Cox, William O.C.M. Cookson, Diana Bilton, Miriam F. Moffatt
Journal: European Respiratory Journal (2013)

A molecular comparison of microbial communities in bronchiectasis and cystic fibrosisTo the Editor:Chronic bacterial infections play an important role in disease progression in patients with bronchiectasis (BX) and cystic fibrosis (CF).Although only a few per cent of all bacteria can be cultured routinely in the laboratory [1], most bacteria can be identified through sequencing the variable regions of their 16S rRNA gene [2].DNA studies in patients with CF revealed a more complex microbiota than was identified by standard culture [3,4], leading us to test by sequencing whether BX may have a similarly complex polymicrobial state.Approval was gained from the Brompton, Harefield and NHLI Research Ethics Committee and all subjects provided written consent.We collected sputa from 11 patients with BX (mean¡SD age years 59.6¡11.6)and 10 with CF (mean¡SD age years 30.8¡5.3).An aliquot of sputum was cultured following CF Trust microbiology guidelines [5].Following lysis and DNA extraction we amplified a hyper-variable region of the 16S rRNA gene, and cloned, sequenced and analysed the products as described [6].96 clones were analysed for each patient.Sequences are stored as GenBank accession numbers JN212577-JN214344.
Thrombin is a therapeutic target for metastatic osteopontin-positive hepatocellular carcinoma
Authors: Yu-Hua Xue, Xiao-Fei Zhang, Qiong-Zhu Dong, Jian Sun, Chun Dai, Hai-Jun Zhou, Ning Ren, Hu-Liang Jia, Qin-Hai Ye, Lun-Xiu Qin
Journal: Hepatology (2010)

We previously identified osteopontin (OPN) as a promoter and thus a potential therapeutic target for hepatocellular carcinoma (HCC) metastasis. The serine protease thrombin interacts with OPN and can modify its biological activity. To explore the role of thrombin alone or in conjunction with OPN in HCC, we studied the correlation of thrombin levels to HCC prognosis in patients with various OPN levels, and evaluated the effects of OPN fragments generated by thrombin cleavage on proliferation and adhesion of HCC cells. We found that the thrombin level was strongly associated with the metastatic potential of HCC cell lines, and that thrombin was remarkably overexpressed in HCC tissue compared with adjacent nontumor tissue. In addition, HCC tissue from patients with recurrent disease displayed much higher thrombin levels, particularly in those with elevated OPN levels. Only HCCs with elevated OPN levels had a significant correlation between high thrombin levels and overall survival (OS; P < 0.01), or time to recurrence (TTR; P < 0.0001) of HCC. Multivariate analysis revealed that thrombin was an independent prognostic indicator. In vitro assays demonstrated that thrombin promotes the proliferation and adhesion of OPN+ HCC cells. Furthermore, thrombin activated the focal adhesion kinase (FAK) pathway of OPN+ HCC cells, which was blocked by the inhibition of integrin β1.Thrombin plays an important role in OPN-mediated aggressive phenotype of HCC through activation of integrin β1-FAK signaling, and is an independent poor prognostic factor for HCC. Thus, thrombin may be a potential therapeutic target to inhibit HCC metastasis in OPN+ patients.