tbuckley/cabot-search huggingface dataset:
Reoperation rates after breast conserving surgery for breast cancer among women in England: retrospective study of hospital episode statistics
Authors: R. Jeevan, D. A. Cromwell, M. Trivella, G. Lawrence, O. Kearins, J. Pereira, C. Sheppard, C. M. Caddy, J. H. P. van der Meulen
Journal: BMJ (2012)

<b>Objectives</b> To examine whether rate of reoperation after breast conserving surgery is associated with patients' characteristics and investigate whether reoperation rates vary among English NHS trusts. <b>Design</b> Cohort study using patient level data from hospital episode statistics. <b>Setting</b> English NHS trusts. <b>Participants</b> Adult women who had breast conserving surgery between 1 April 2005 and 31 March 2008. <b>Main outcome measure</b> Reoperation rates after primary breast conserving surgery within 3 months, adjusted using logistic regression for tumour type, age, comorbidity, and socioeconomic deprivation. Tumours were grouped by whether a carcinoma in situ component was coded at the time of the primary breast conserving surgery. <b>Results</b> 55 297 women had primary breast conserving surgery in 156 NHS trusts during the three year period. 11 032 (20.0%, 95% confidence interval 19.6% to 20.3%) women had at least one reoperation. 10 212 (18.5%, 18.2% to 18.8%) had one reoperation only; of these, 5943 (10.7%, 10.5% to 11.0%) had another breast conserving procedure and 4269 (7.7%, 7.5% to 7.9%) had a mastectomy. Of the 45 793 women with isolated invasive disease, 8229 (18.0%) had at least one reoperation. In comparison, 2803 (29.5%) of the 9504 women with carcinoma in situ had at least one reoperation (adjusted odds ratio 1.9, 95% confidence interval 1.8 to 2.0). Substantial differences were found in the adjusted reoperation rates among the NHS trusts (10th and 90th centiles 12.2% and 30.2%). <b>Conclusion</b>: One in five women who had breast conserving surgery in England had a reoperation. Reoperation was nearly twice as likely when the tumour had a carcinoma in situ component coded. Women should be informed of this reoperation risk when deciding on the type of surgical treatment of their breast cancer.
Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF
Authors: J. Andersson, L. Larsson, S. Klaar, L. Holmberg, J. Nilsson, M. Inganäs, G. Carlsson, J. Öhd, C.-M. Rudenstam, B. Gustavsson, J. Bergh
Journal: Annals of Oncology (2005)
New Mechanisms for Vascular Control of Inflammation Mediated by Natural Anticoagulant Proteins
Authors: Charles T. Esmon
Journal: The Journal of Experimental Medicine (2002)

It has been appreciated for a very long time that infections, particularly bacterial infections of the blood leading to severe sepsis, trigger a hypercoaguable state that sometimes leads to overt disseminated intravascular coagulation. We now recognize that endotoxins and other bacterial, fungal,
Diffuse-Type Gastric Carcinoma: Progression, Angiogenesis, and Transforming Growth Factor β Signaling
Authors: Akiyoshi Komuro, Masakazu Yashiro, Caname Iwata, Yasuyuki Morishita, Erik Johansson, Yoshiko Matsumoto, Akira Watanabe, Hiroyuki Aburatani, Hiroyuki Miyoshi, Kunihiko Kiyono, Yo-taro Shirai, Hiroshi I. Suzuki, Kosei Hirakawa, Mitsunobu R. Kano, Kohei Miyazono
Journal: JNCI Journal of the National Cancer Institute (2009)

Diffuse-type gastric carcinoma is a cancer with poor prognosis that has high levels of transforming growth factor beta (TGF-beta) expression and thick stromal fibrosis. However, the association of TGF-beta signaling with diffuse-type gastric carcinoma has not been investigated in detail.We used a lentiviral infection system to express a dominant-negative TGF-beta type II receptor (dnTbetaRII) or green fluorescent protein (GFP) as a control in the diffuse-type gastric carcinoma cell lines, OCUM-2MLN and OCUM-12. These infected cells and the corresponding parental control cells were subcutaneously or orthotopically injected into nude mice. Angiogenesis was inhibited by infecting cells with a lentivirus carrying the gene for angiogenic inhibitor thrombospondin-1 or by injecting mice intraperitoneally with the small-molecule angiogenic inhibitor sorafenib or with anti-vascular endothelial growth factor (VEGF) neutralizing antibody (six or eight mice per group). Expression of phospho-Smad2 and thrombospondin-1 was investigated immunologically in human gastric carcinoma tissues from 102 patients. All statistical tests were two-sided.Expression of dnTbetaRII into OCUM-2MLN cells did not affect their proliferation in vitro, but it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo (eg, for mean volume of subcutaneous tumors on day 10 relative to that on day 0: dnTbetaRII tumors = 3.49 and GFP tumors = 2.46, difference = 1.02, 95% confidence interval [CI] = 0.21 to 1.84; P = .003). The tumors expressing dnTbetaRII had higher levels of angiogenesis than those expressing GFP because of decreased thrombospondin-1 production. Similar results were obtained with OCUM-12 cells. Expression of thrombospondin-1 in the dnTbetaRII tumor or treatment with sorafenib or anti-VEGF antibody reduced tumor growth, whereas knockdown of thrombospondin-1 expression resulted in more accelerated growth of OCUM-2MLN tumors than of GFP tumors (eg, mean tumor volumes on day 14 relative to those on day 0: thrombospondin-1-knockdown tumors = 4.91 and GFP tumors = 3.79, difference = 1.12, 95% CI = 0.80 to 1.44; P < .001). Positive association between phosphorylated Smad2 and thrombospondin-1 immunostaining was observed in human gastric carcinoma tissues.Disruption of TGF-beta signaling in diffuse-type gastric carcinoma models appeared to accelerate tumor growth, apparently through increased tumor angiogenesis that was induced by decreased expression of thrombospondin-1.
A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03
Authors: Fabio M. Iwamoto, Kathleen R. Lamborn, John G. Kuhn, Patrick Y. Wen, W.K. Alfred Yung, Mark R. Gilbert, Susan M. Chang, Frank S. Lieberman, Michael D. Prados, Howard A. Fine
Journal: Neuro-Oncology (2011)

Romidepsin, a potent histone deacetylase inhibitor, has shown activity in preclinical glioma models. The primary objectives of this trial were to determine the pharmacokinetics of romidepsin in patients with recurrent glioma on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of romidepsin in patients with recurrent glioblastoma who were not receiving EIAEDs. Two dose cohorts were studied in the phase I component of the trial (13.3 and 17.7 mg/m2/d). Patients in the phase II component were treated with intravenous romidepsin at a dosage of 13.3 mg/m2/day on days 1, 8, and 15 of each 28-day cycle. Eight patients were treated on the phase I component. A similar romidepsin pharmacokinetic profile was demonstrated between patients receiving EIAEDs to those not receving EIAEDs. Thirty-five patients with glioblastoma were accrued to the phase II component. There was no objective radiographic response. The median progression-free survival (PFS) was 8 weeks and only 1 patient had a PFS time ≥6 months (PFS6 = 3%). To date, 34 patients (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that romidepsin is primarily metabolized by CYP3A4, no decrease in exposure to romidepsin was seen in patients receiving potent CYP3A4 inducers. Romidepsin, at its standard dose and schedule, was ineffective for patients with recurrent glioblastomas. ClinicalTrials.gov identifier: NCT00085540.
Polymorphisms in NOS-1 and NOS-3 genes may influence the cystic fibrosis severity?
Authors: Fernando Marson, Carmen Bertuzzo, Antonio Ribeiro, Jose Ribeiro
Journal: European Respiratory Journal (2014)

Introduction: Cystic fibrosis(CF) has clinical variability associated with  CFTR  mutations, environmental factors and modifier genes, including genes associated with the nitric oxide pathway.  Objective: To compare the CF severity with tandem repeat polymorphisms of the  NOS-1  gene(AAT, TG1 and TG2) and -894G>T polymorphism in  NOS-3  plus  CFTR  mutations by a bioinformatic tool.  Method: 180 CF patients were included. The  NOS-1  polymorphisms were analyzed in MegaBace1000 ®  and  NOS-3  by RFLP. Clinical markers: sex, scores[Shwachman-Kulczycki, Kanga and Bhalla(EB)], BMI, age, age at diagnosis, initial symptoms, first colonization by  Pseudomonas aeruginosa (PA), colonization by microorganisms[PA mucoid and non- mucoid,  Achromobacter xylosoxidans (AX),  Staphylococcus aureus ,  Burkolderia cepacia (BC)], SpO2, spirometry and comorbidities[nasal polyposis, pancreatic insufficiency, meconium ileus(MI), osteoporosis(O) and diabetes mellitus(DB)]. Statistical analysis: Fisher9s exact, Mann-Whitney, Multifactor Dimensionalitty Reduction Test v2.0.  Results: AAT= minor number of repetitions for allele 1(≤ 10) was associated with lower FEF25-75% and frequency of AX. Minor repetitions(≤1 ) in allele 2 was associated with higher frequency of MI. TG1= minor repetitions for allele 1(≤ 17) was associated with lower FEV1%, late onset of pulmonary disease, higher incidence of O. TG2= minor repetitions in allele 2(≤30) was associated with lower frequency of DB and BC, and higher FEV1/FVC. The T allele for the -894G>T was associated with early lung disease. There was gene interaction between TG1 and TG2 polymorphism plus  CFTR  mutations, and EB.  Conclusion: Polymorphisms in  NOS-1  and  NOS-3  gene influence the CF severity.
Long-term effects of strontium-89 combined with chemotherapy in patients with androgen-independent prostate cancer and bone metastases
Authors: S.-M. Tu, J. Kim, L. C. Pagliaro, F. Vakar-Lopez, F. C. Wong, S. Wen, R. General, D. A. Podoloff, S.-H. Lin, C. J. Logothetis
Journal: Journal of Clinical Oncology (2005)

4671 Background: Although strontium-89 has been used for the treatment of bone metastases, its long-term effects remain unclear. We assessed the rate of bone marrow failure in patients with prostate cancer who had received a dose of strontium-89. Methods: This subgroup analysis involved 34 patients with androgen-independent prostate cancer and bone metastases who had been given a dose of strontium-89 and six weekly doses of doxorubicin for consolidation after response to induction chemotherapy. We assessed subsequent hematotoxicity in terms of bone marrow failure and the ability to tolerate additional treatments during a median 25 months (range, 7–76 months) after the strontium-89 treatment. Results: No patients developed bone marrow failure within 6 months of receiving strontium-89. Five (15%) of 34 patients developed bone marrow failure at a median 23 months (range, 6–53 months) after the strontium-89 treatment. Bone marrow biopsy was performed in two of these five patients and showed complete replacement of the marrow by tumor in both patients. Thirty-one (91%) patients were able to undergo subsequent cytotoxic treatments at a median 11 months (range, 1–33 months) after receiving the single dose of strontium-89. Conclusions: This analysis suggested that a single dose of strontium-89 given in combination with doxorubicin rarely caused bone marrow failure and did not affect the ability to tolerate subsequent treatments among patients with androgen-independent prostate cancer and bone metastases that had responded to induction chemotherapy. The few cases of bone marrow failure were likely to have been caused by tumor infiltration rather than by a treatment effect. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Corixa, GE Healthcare, IDEC, Siemens Corixa, GE Healthcare, IDEC, Siemens Corixa, GE Healthcare, IDEC, Siemens
Update on therapeutic neovascularization
Authors: Y CAO, A HONG, H SCHULTEN, M POST
Journal: Cardiovascular Research (2004)

Therapeutic neovascularization for cardiovascular ischemia is a promising avenue in spite of disappointing early clinical trial results. The concept of three different mechanisms of neovascularization has served to define potential therapeutic targets such as vascular remodeling and stem cell recruitment, but it is anticipated that this will lose significance as the pleiotropic nature of angiogenic cytokines becomes fully understood. With the rapidly growing body of data on growth factors and pro-angiogenic strategies, approaches will emerge that are more effective than the ones that have been tested clinically thus far. Combinations of growth factors, for instance to stabilize vessels, or growth factors combined with cell transplants deserve more attention but will make the design of preclinical and clinical studies increasingly complex. Recent developments suggest that when using the appropriate dose and treatment regimens, even single growth factor therapy can result in stable and functional vessels. Whether gene therapy or protein therapy will be optimal for this purpose depends mainly on technical developments in vector design and production and on progress in the engineering of slow release matrix formulations for proteins. With the increasing complexity of therapeutic strategies, it remains imperative that these approaches are rationally based on fundamental and preclinical data.
National survey of UK emergency endoscopy units
Authors: Andrew Douglass, Michael G Bramble, Ian Barrison
Journal: BMJ (2005)

been used to employ 7700 therapists (26 per primary care trust in England) providing 1.54 million treatment courses of six sessions each a year.This estimate increases to 2.43 million if the therapy is delivered by a graduate mental health worker and falls to 0.51 million if the course of treatment is lengthened to 18 sessions.
Synergistic Inhibition with a Dual Epidermal Growth Factor Receptor/HER-2/neu Tyrosine Kinase Inhibitor and a Disintegrin and Metalloprotease Inhibitor
Authors: Lois Witters, Peggy Scherle, Steven Friedman, Jordan Fridman, Eian Caulder, Robert Newton, Allan Lipton
Journal: Cancer Research (2008)

The ErbB family of receptors is overexpressed in numerous human tumors. Overexpression correlates with poor prognosis and resistance to therapy. Use of ErbB-specific antibodies to the receptors (Herceptin or Erbitux) or ErbB-specific small-molecule inhibitors of the receptor tyrosine kinase activity (Iressa or Tarceva) has shown clinical efficacy in several solid tumors. An alternative method of affecting ErbB-initiated tumor growth and survival is to block sheddase activity. Sheddase activity is responsible for cleavage of multiple ErbB ligands and receptors, a necessary step in availability of the soluble, active form of the ligand and a constitutively activated ligand-independent receptor. This sheddase activity is attributed to the ADAM (a disintegrin and metalloprotease) family of proteins. ADAM 10 is the main sheddase of epidermal growth factor (EGF) and HER-2/neu cleavage, whereas ADAM17 is required for cleavage of additional EGF receptor (EGFR) ligands (transforming growth factor-alpha, amphiregulin, heregulin, heparin binding EGF-like ligand). This study has shown that addition of INCB3619, a potent inhibitor of ADAM10 and ADAM17, reduces in vitro HER-2/neu and amphiregulin shedding, confirming that it interferes with both HER-2/neu and EGFR ligand cleavage. Combining INCB3619 with a lapatinib-like dual inhibitor of EGFR and HER-2/neu kinases resulted in synergistic growth inhibition in MCF-7 and HER-2/neu-transfected MCF-7 human breast cancer cells. Combining the INCB7839 second-generation sheddase inhibitor with lapatinib prevented the growth of HER-2/neu-positive BT474-SC1 human breast cancer xenografts in vivo. These results suggest that there may be an additional clinical benefit of combining agents that target the ErbB pathways at multiple points.
Future of singlehanded general practices: All doctors must show that they work to acceptable standards
Authors: N Ken Menon
Journal: BMJ (2005)

EDITOR—Singlehanded general practice and the work of singlehanders in general practice have been in the news in the recent years after the events relating to the late Harold Shipman and the various inquiries that have resulted. That Shipman was a killer is now incontrovertible; that he was a …
An abnormal gene expression of the β-adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats
Authors: Giulio Ceolotto, Italia Papparella, Antonietta Sticca, Sergio Bova, Maurizio Cavalli, Gabriella Cargnelli, Andrea Semplicini, Angelo Gatta, Paolo Angeli
Journal: Hepatology (2008)

Decreased cardiac contractility and beta-adrenergic responsiveness have been observed in cirrhotic cardiomyopathy, but their molecular mechanisms remain unclear. To study beta-adrenergic-stimulated contractility and beta-adrenergic gene expression patterns, 20 Wistar Kyoto rats were treated with carbon tetrachloride to induce cirrhosis and 20 rats were used as controls. Left ventricular contractility was recorded in electrically driven isolated hearts perfused at constant flow with isoproterenol (10(-10) to 10(-6) M). A cardiac gene expression profile was obtained using a microarray for the myocyte adrenergic pathway. The cardiac contractility maximal response to isoproterenol was significantly reduced in cirrhotic rats in comparison to control rats, whereas the half-maximal effective concentration was not different. In cirrhotic rats, cardiac gene expression analysis showed a significant overexpression of G protein alpha-inhibiting subunit 2 (Galpha(i2)), cyclic nucleotide phosphodiesterase (PDE2a), regulator of G-protein signaling 2 (RGS2), and down-expression of adenylate cyclase (Adcy3). These results indicate that overexpression of Galpha(i2), PDE2a, and RGS2 down-regulates the beta-adrenergic signaling pathway, thus contributing to the pathogenesis of cirrhotic cardiomyopathy.
Palliative Care and Oncology: Growing Better Together
Authors: Ira Byock
Journal: Journal of Clinical Oncology (2008)

palliative care physicians (37.3%), social work (29.3%), physical or occupational therapy (12%), and psychology or psychiatry (10%). The report does not delineate the extent of care planning and patient and caregiver counseling offered during these visits. In addition to managing symptoms, palliative care teams commonly assist patients and families with clarifying goals of care; support decision makingregardingtreatmentoptions;andcreatetailoredcrisispreven
PSTPIP2 deficiency in mice causes osteopenia and increased differentiation of multipotent myeloid precursors into osteoclasts
Authors: Violeta Chitu, Viorel Nacu, Julia F. Charles, William M. Henne, Harvey T. McMahon, Sayan Nandi, Halley Ketchum, Renee Harris, Mary C. Nakamura, E. Richard Stanley
Journal: Blood (2012)
Tuberculin and Anergy Testing in HIV-Seropositive and HIV-Seronegative Persons
Authors: Norman Markowitz
Journal: Annals of Internal Medicine (1993)

Objective: To determine the prevalence and predictors of reactivity to tuberculin purified protein derivative (PPD) and skin test anergy in patients with human immunodeficiency virus (HIV) infection and in HIV-seronegative controls. Design: Cross-sectional analysis of baseline data from a prospective, multicenter study of pulmonary complications of HIV infection. Setting: Community-based cohort of persons with and without HIV infection. Patients: A total of 1171 HIV-seropositive patients without AIDS (841 homosexual men, 274 intravenous drug users, and 56 women with heterosexually acquired infection); 182 HIV-seronegative persons (125 homosexual men and 57 intravenous drug users). Measurements: Delayed-type hypersensitivity response to tuberculin PPD, trichophytin, mumps, and Candida antigens; T-lymphocyte subsets. Results: The prevalence of tuberculin PPD reactivity was higher among intravenous drug users than among homosexual men, in both HIV-seronegative (19.1% compared with 6.8%, P = 0.03) and HIV-seropositive persons (15.1% compared with 2.5%, P < 0.001). Among HIV-infected patients, the prevalence of tuberculin reactivity varied directly and that of anergy inversely with the absolute CD4 lymphocyte count. Prevalences were 1% and 72%, respectively, in patients with fewer than 200 CD4 cells/mm3, and 8.4% and 25.5%, respectively, in those with 600 CD4 cells/mm3 (P < 0.001 for both comparisons). Patients with HIV infection and fewer than 400 CD4 lymphocytes/mm3 had a lower prevalence of PPD reactivity than HIV-seronegative controls (2.7% compared with 10.0%, P < 0.001). The strongest predictors of tuberculin reactivity were intravenous drug use, black race, a previous positive PPD test result, and a history of CalmetteGurin bacillus vaccination. The strongest predictor of anergy was HIV seropositivity. Conclusions: The response to delayed-type hypersensitivity antigens depends on immune status. The value of PPD and anergy testing in HIV-seropositive patients depends on the ability of such testing to predict subsequent tuberculosis, which is imprecisely known. Until more data or better methods are available, these tests should be done as early as possible in the course of HIV infection. *For participating institutions and investigators, see the Appendix.
An alternative classification system for chronic kidney disease
Authors: G. Van Pottelbergh, J. M. Degryse
Journal: BMJ (2013)

We have several comments on Moynihan and colleagues’ excellent article about the overdiagnosis of chronic kidney disease (CKD).1

Firstly, two large cohort studies with long follow-up have shown that the chance of developing adverse outcomes (mortality or need for renal replacement therapy) is much lower in older age groups.2 3 This finding was confirmed in a large meta-analysis …
Responses of Coronary Smooth Muscle to Catecholamines
Authors: RICARDO C. ZUBERBUHLER, DAVID F. BOHR
Journal: Circulation Research (1965)

Responses to catecholamines were studied in isolated helical muscle strips of large and small coronary vessels and in isolated perfused coronary arteries from the dog. Epinephrine and norepinephrine in concentrations well below those normally present in the blood uniformly caused relaxation of small coronary vessels. Norepinephrine was much more potent than epinephrine. The relaxation was reversibly blocked by the beta adrenergic blocker, nethalide. During this blockade, catecholamines either were inactive or produced a slight contraction. Strips contracted by angiotensin, blood or KCl, as well as those completely depolarized by K 2 SO 4 , were relaxed by catecholamines. Strips taken from large coronary vessels, unlike those from small vessels, were, in some cases, contracted by catecholamines; in others, after a transient contraction, they were relaxed. Contraction was blocked by Dibenzyline. This difference in behavior of large and small vessels may account for some of the contradictions found in the literature concerning the response of coronary vessels to catecholamines.