tbuckley/cabot-search huggingface dataset:
The Address Delivered in the Section of Surgery
Authors: W. S. Savory
Journal: BMJ (1880)

I! I yielde(d to miiy inclination, I should remain silent in this chair, or merely invite you, without preface, to proceed at once to the business of this section ; but, fearing that such silence should suggest to any one that I do not fully appreciate the honour of being in this place, I will venture to trouble you with a few remarks.But I shall take care that tlhey are very brief, and that they are confined to surgery; and I select the subject of Constitutional Disturbance.The phrase, "constitutional disturbance", in its application to thle effect of local disease or injury, has b)ecn always a good one; and (lown almost to our oNvn timiie it has, in relation to our knowlecdge of the subject, been sufficiently precise.But of late, especially, it has become evident that this familiar expression is too comprehensive, and covers widely different states, and of these the two principal ones require to be careftlly distinguished.It might be made abundantly clear by refer- ence to the literature of the period, particularly to the works of HIunter, Abernethy, and Travcrs, that for many years the belief prevailed that distthrbance of the whole body, or the illness produced by local iiischief, was evoked through the nervous system-and hence the phrases, " sympathetic inflammatory fever", " constitutional irritation"; and this great doctrine naturally grew in force as the functions of the nervouis system came to be better understood.The discovery of reflex function went very far to explain the mode of action of the nervous system as the channel of sympathy between the various structures and organs of the body.But then came the knowledge of what is now known as "bloodpoisoning"; and from the time, not far distant, when this first dawned on the minds of surgeons, it has become so rapidly developed that now it threatens to, nay, it actually does, exclude the older view; so that with many, at the present time, constitutional disturbance in this relation means always the phenomena of blood-poisoning, in some one dr other of its various forms.My object, in the few remarks I would subnmit to you to-day, is to
Abstract 2031: HMGB1 regulates pancreatic cancer initiation and pogression
Authors: Rui Kang, Qiuhong Zhang, Wen Hou, Ruochan Chen, Michael Lotze, Herbert Zeh, Daolin Tang
Journal: Cancer Research (2014)

Abstract Most pancreatic ductal adenocarcinoma (PDAC), an almost uniformly lethal disease, is thought to arise from well-defined, non-invasive precursor lesions, termed pancreatic ductal intraepithelial neoplastic lesions (PanINs). Studies of human pancreatic carcinogenesis have been greatly facilitated by the development of a genetically engineered mouse model that expresses oncogenic K-Ras under a pancreatic promoter Pdx1-Cre:KrasG12D/+. A more detailed understanding of how this pathway accelerates pancreatic carcinogenesis may allow improved early detection, prevention, and therapeutic strategies. Our recent studies demonstrate that high mobility group box 1 (HMGB1) is a critical regulator of autophagy, a major pathway for degradation of effete proteins and damaged organelles. We found that conditional genetic ablation of HMGB1 limited to the pancreas (Pdx1-Cre;K-Ras G12D/+;HMGB1-/-; termed KCH mice) inhibits autophagy, promotes proliferation, activates normally quiescent pathways, and renders mice extraordinarily sensitive to K-RasG12D/+-driven pancreatic carcinogenesis. We found that the progression of PanINs from low grade PanIN1 to high grade PanIN3 was observed as early as three-seven days (normally three-nine months) after birth in KCH mice, suggesting a critical role of HMGB1 in regulation of the earliest events during pancreatic carcinogenesis. This extraordinarily rapid murine pancreatic cancer model that we have created will allow us to dissect the mechanism by which loss of HMGB1 contributes to the process. Citation Format: Rui Kang, Qiuhong Zhang, Wen Hou, Ruochan Chen, Michael Lotze, Herbert Zeh, Daolin Tang. HMGB1 regulates pancreatic cancer initiation and pogression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2031. doi:10.1158/1538-7445.AM2014-2031
Induction of leukemia-specific CD8+ cytotoxic t cells with autologous myeloid leukemic cells maturated with a fiber-modified adenovirus encoding TNF-α
Authors: Aurore Saudemont, Selim Corm, Thomas Wickham, Dominique Hetuin, Bruno Quesnel
Journal: Molecular Therapy (2005)

Acute myeloid leukemia (AML) cells can be differentiated into dendritic cells (DCs) using appropriate combinations of cytokines but generation of autologous antileukemic cytotoxic T cells using leukemic DCs remains difficult. Transduction by adenoviral vectors has been reported to induce efficient maturation of monocyte-derived DCs but AML cells are generally resistant to adenoviral gene transfer. In this study we tested the effects of adenoviral TNF-alpha gene transfer on maturation of AML cells using the fiber-modified AdTNF.F(pK7) adenovirus. All samples expressed high and sustained levels of TNF-alpha following transduction. AdTNF.F(pK7) induced significantly greater maturation of AML cells into antigen-presenting cells (APC) than did recombinant TNF-alpha or control adenoviral vector. Maturation of leukemic cells into APCs was mediated at least partially via a PI3K/mTOR pathway, as the inhibitors LY294002, wortmannin, and rapamycin inhibited the maturation effect induced by the AdTNF.F(pK7) adenovirus. In addition, CD8+ T cells expanded with AdTNF.F(pK7)-transduced AML cells showed greater expansion and specific CD8+ CTL activity against autologous AML cells than T cells expanded by other means. Thus, fiber-modified adenoviral vectors encoding TNF-alpha are able to maturate AML cells into APCs with high efficacy and reproducibility, providing a useful tool to generate efficiently specific CD8+ CTLs against leukemic disease.
Discontinuation of Statins in Routine Care Settings
Authors: Huabing Zhang, Jorge Plutzky, Stephen Skentzos, Fritha Morrison, Perry Mar, Maria Shubina, Alexander Turchin
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: Systematic data on discontinuation of statins in routine practice of medicine are limited. Objective: To investigate the reasons for statin discontinuation and the role of statin-related events (clinical events or symptoms believed to have been caused by statins) in routine care settings. Design: A retrospective cohort study. Setting: Practices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital in Boston. Patients: Adults who received a statin prescription between 1 January 2000 and 31 December 2008. Measurements: Information on reasons for statin discontinuations was obtained from a combination of structured electronic medical record entries and analysis of electronic provider notes by validated software. Results: Statins were discontinued at least temporarily for 57 292 of 107 835 patients. Statin-related events were documented for 18 778 (17.4%) patients. Of these, 11 124 had statins discontinued at least temporarily; 6579 were rechallenged with a statin over the subsequent 12 months. Most patients who were rechallenged (92.2%) were still taking a statin 12 months after the statin-related event. Among the 2721 patients who were rechallenged with the same statin to which they had a statin-related event, 1295 were receiving the same statin 12 months later, and 996 of them were receiving the same or a higher dose. Limitations: Statin discontinuations and statin-related events were assessed in practices affiliated with 2 academic medical centers. Utilization of secondary data could have led to missing or misinterpreted data. Natural-language–processing tools used to compensate for the low (30%) proportion of reasons for statin discontinuation documented in structured electronic medical record fields are not perfectly accurate. Conclusion: Statin-related events are commonly reported and often lead to statin discontinuation. However, most patients who are rechallenged can tolerate statins long-term. This suggests that many of the statin-related events may have other causes, are tolerable, or may be specific to individual statins rather than the entire drug class. Primary Funding Source: National Library of Medicine, Diabetes Action Research and Education Foundation, and Chinese National Key Program of Clinical Science.
Serial angiographic assessment of coronary artery obstruction and collateral flow in acute myocardial infarction. Report from the second Mount Sinai-New York University Reperfusion Trial.
Authors: K P Rentrop, F Feit, W Sherman, J C Thornton
Journal: Circulation (1989)

In the Second Mt. Sinai-New York University Reperfusion Trial, in which change of ejection fraction was the primary end point, the following secondary end points were prospectively assessed by serial coronary angiography: patency of the infarct artery both before intervention and 10-14 days later, acute and delayed recanalization rates, presence or absence of collateral flow, and complication rates of acute interventional catheterization. We assigned 393 patients randomly to groups receiving acute cardiac catheterization and a double-blind intracoronary infusion of streptokinase (SK arm), both streptokinase and nitroglycerin (SK-NTG arm), nitroglycerin alone (NTG arm), or conventional therapy without acute catheterization (control arm). Prospective stratification was based on duration of infarct pain before randomization: group A, less than 2 hours; Group B, 2-12 hours. Baseline patency rates were comparable in patients studied within 6 hours (30%, 40 of 135) and those studied later (24%, 32 of 133). This finding refutes the hypothesis that spontaneous recanalization occurs frequently after 6 hours. The acute recanalization rates of the SK arm (60%, 40 of 67) and the SK-NTG arm (63%, 29 of 62) did not differ. During streptokinase infusion, more vessels recanalized in group A (81%, 22 of 27) than in group B (56%, 57 of 102) (p less than 0.01); this was due to a significant reduction of recanalization rates from 75% (48 of 64) to 45% (26 of 62) with treatment after 6 hours (p less than 0.01). Delayed recanalization, that is, patency at end point but not postintervention, was seen in 17% (17 of 100) of total occlusions treated with streptokinase. In group A, all total occlusions treated with streptokinase recanalized either acutely (20 of 22) or delayed (two of 22), whereas in group B, 23% (18 of 78) remained obstructed. The reocclusion rate in the SK arms was 17% (11 of 65). In the NTG arm, recanalization occurred during intervention in 4% (two of 47) and delayed in 45% (21 of 47). At end-point angiography, the patency rates of the NTG arm (62%, 41 of 66) and the control arm (58%, 36 of 62) were comparable; those of the SK arms were higher (75%, 105 of 140) (p less than 0.01). Total occlusion was associated with collateral flow in 33% (66 of 199) at baseline; the prevalence of collaterals did not increase with time to angiography, which indicates that they had developed before the index event.(ABSTRACT TRUNCATED AT 400 WORDS)
Lesions Observed in Arterial Autogenous Vein Grafts
Authors: MICHAEL JONES, DAVID M. CONKLE, VICTOR J. FERRANS, WILLIAM C. ROBERTS, FREDERICK H. LEVINE, DAVID B. MELVIN, EDWARD B. STINSON
Journal: Circulation (1973)

Autogenous vein grafts used for canine femoral and aortocoronary arterial bypasses were evaluated from 2 to 365 days postoperatively. Femoral grafts showed focal endothelial disruption, mural fibrin deposition, and medial edema with inflammatory infiltrates during the first week; loss of medial smooth muscle cells and focal subendothelial lesions with intact endothelium by 2 weeks; and diffuse subendothelial lesions by 12 weeks, Coronary grafts studied at 6, 9, and 12 months had medial fibrosis and extensive intimal proliferation causing up to 90% luminal narrowing. Extension of the intimal process into the coronary artery distal to the bypass graft also compromised the arterial lumen. Coronary grafts obtained from humans dying 17 and 57 days after graft insertion revealed a similar subendothelial proliferation. Electron microscopy showed that the subendothelial lesions were composed of mature smooth muscle cells and collagen primarily oriented parallel to the axis of blood flow. Recurrent endothelial cell damage, followed by mural fibrin deposition and organization, appears to be the cause of the subendothelial proliferative lesions.
Characterization of the tissue macrophage and the interstitial dendritic cell as distinct leukocytes normally resident in the connective tissue of rat heart.
Authors: S C Spencer, J W Fabre
Journal: The Journal of Experimental Medicine (1990)

Immunohistological studies with a mouse anti-rat macrophage mAb (BMAC-5) demonstrated the presence of numerous positive cells in the interstitial connective tissues of many organs. The pattern resembled that seen with anti-MHC class II antibodies, with the striking exception that BMAC-5+ cells were rare or absent in the portal triad, the islets of Langerhans, and the kidney. Double-labeling fluorescence studies were therefore performed in rat heart using the BMAC-5 mAb in combination with rabbit antisera to pure rat class II MHC antigens and pure rat leukocyte common (CD45) antigens. The tissue macrophages in heart were identified as BMAC-5+, MHC class II-negative, leukocyte common antigen-positive cells. They could be distinguished from the BMAC-5-, MHC class II-positive, leukocyte common antigen-positive interstitial dendritic cells. Moreover, 7 d after lethal irradiation, the class II-positive interstitial dendritic cells had completely disappeared from heart, whereas the BMAC-5+ macrophages were present in undiminished numbers. These studies strongly suggest that the interstitial dendritic cell and the tissue macrophage represent two distinct populations of leukocytes within the connective tissues of antigenically secluded organs such as the heart. They have potentially important implications for the physiology of the immune system, as well as for autoimmunity and transplantation.
Soy, isoflavones, and prevalence of allergic rhinitis in Japanese women: The Osaka Maternal and Child Health Study
Authors: Yoshihiro Miyake, Satoshi Sasaki, Yukihiro Ohya, Shoichi Miyamoto, Ichiro Matsunaga, Toshiaki Yoshida, Yoshio Hirota, Hajime Oda, None the Osaka Maternal and Child Health Study Group
Journal: Journal of Allergy and Clinical Immunology (2005)
Treatment for advanced prostate cancer can turn from helpful to harmful, research shows
Authors: N. Hawkes
Journal: BMJ (2014)

Treatments for advanced prostate cancer that combine steroids and hormonal therapy can become actively harmful when the steroids encourage genetic mutations that turn the treatment from an inhibitor to an activator of the disease, a team from the Institute of Cancer Research in London and the University of Trento in Italy has found.

This change can be tracked by analysing blood samples for circulating tumour DNA, allowing treatment …
TCTAP A-085 What Stent Diameter Should We Select in Order to Prevent from Stent Edge Dissection in OCT-guide?
Authors: Hiroyuki Shibata, Yochi Kijima, Tomoya Masano, Ryoji Nagoshi, Kozuki Amane, Kimitake Imamura, Jyunya Shite
Journal: Journal of the American College of Cardiology (2014)
Recovery and Long-term Function After Hematopoietic Cell Transplantation for Leukemia or Lymphoma
Authors: Karen L. Syrjala
Journal: JAMA (2004)

Hematopoietic cell transplantation (HCT) is an effective and widely used treatment for hematologic malignancies. The rate and predictors of physical and emotional recovery after HCT have not been adequately defined in prospective long-term studies.To examine the course of recovery and return to work after HCT.Prospective, longitudinal cohort study at a US academic center specializing in HCT. Function was assessed from pretransplantation to 5-year follow-up for 319 adults who had myeloablative HCT for treatment of leukemia or lymphoma and spoke English. Of the 99 long-term survivors who had no recurrent malignancy, 94 completed 5-year follow-up.Physical limitations, return to work, depression, and distress related to treatment or disease were evaluated before transplantation, at 90 days, and at 1, 3, and 5 years after HCT.Physical recovery occurred earlier than psychological or work recovery. Only 21 patients (19%) recovered on all outcomes at 1 year. The proportion without major limitations increased to 63% (n = 57) by 5 years. Among survivors without recurrent malignancy, 84% (n = 74) returned to full-time work by 5 years. Patients with slower physical recovery had higher medical risk and were more depressed before HCT (P< or =.001). Patients with chronic graft-vs-host disease (P =.01), with less social support before HCT (P =.001), and women (P<.001) were more depressed after transplantation. Transplant-related distress was slower to recover for allogeneic transplant recipients and those with less social support before HCT (P< or =.01). Patients who had more experience with cancer treatment before beginning HCT had more rapid recovery from depression (P =.04) and treatment-related distress (P =.009).Full recovery after HCT is a 3- to 5-year process. Recovery might be accelerated by more effective interventions to increase work-related capabilities, improve social support, and manage depression.
847 PHASE II STUDY OF THE MITOCHONDRIAL ANTIOXIDANT MITOQUINONE FOR HEPATITIS C
Authors: E.J. Gane, D.W. Orr, F. Weilert, G.F. Keogh, M. Gibson, M.P. Murphy, R.A. Smith, M.M. Lockhart, C.M. Frampton, K.M. Taylor
Journal: Journal of Hepatology (2008)
Abstract P5-19-01: Targeting the HER3-phosphatidyl inositol-3 kinase pathway in breast cancers
Authors: RS Cook, MM Morrison, CL Arteaga, CM Perou
Journal: Cancer Research (2012)

Abstract Background: Using a mouse model of HER3 ablation in the mammary epithelium, we previously showed that HER3 is required for the genesis of transgenic HER2-overexpressing breast cancers. However, increasing evidence suggests that transgenic models of HER2 overexpression result in luminal B-like mammary tumors, which resemble human breast tumors that express estrogen receptor (ER) but are often not responsive to endocrine therapy. Furthermore, we found that HER3 is required in the untransformed mouse mammary epithelium for differentiation and survival of luminal cells, but not basal cells. Herein we report that HER3 drives growth and survival of luminal breast cancers in a manner that parallels its role in maintaining the untransformed luminal epithelium in the breast. Results: Expression profiling of a large human breast cancer dataset demonstrated that HER3 expression was highest in Luminal breast cancers as compared to different molecular subtypes of breast cancers, including HER2-enriched, claudin-low, and basal-like breast cancers. In luminal breast cancer cell lines MCF7, ZR75-1, and MDA-MB-361, HER3 targeting using siRNA or a monoclonal antibody against HER3 decreased Akt, S6, and Erk1/2 phosphorylation, cell growth and cell survival under conditions of estrogen deprivation. Luminal breast tumor xenografts treated with U3-1287, a humanized monoclonal anti-ErbB3 antibody, or EZN-3920, an anti-sense oligonucleotide against ErbB3, decreased tumor growth and phosphatidyl inositol-3 kinase (PI3K)/mTOR signaling in vivo. Interestingly, luminal breast tumor xenografts responded to the ER inhibitor fulvestrant with increased HER3 expression and phosphorylation, and with increased PI3K/mTOR signaling as shown by enhanced S6 phosphorylation. Fulvestrant-mediated upregulation of HER3 was also seen in matched clinical breast tumor specimens harvested before treatment and after 21 days of fulvestrant treatment. AMG-888 blocked fulvestrant-induced HER3 and phospho-S6 upregulation in vivo, resulting in regression of luminal breast tumor xenografts. Conclusions: These data suggest that HER3 targeting may improve the outcome of luminal breast cancers treated with endocrine therapy, and are consistent with our findings that a HER3-dependent expression signature positively correlates with relapse in tamoxifen-treated patients. Taken together, these results define a novel role for HER3 in luminal breast cancer cells, and support future investigations into therapeutic strategies to target HER3 in luminal breast cancers. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-19-01.
Paul McIntosh Orgill Massey
Authors: D. B. Eccleston
Journal: BMJ (2010)

Where does one begin to describe this extraordinary man? Paul McIntosh Orgill Massey qualified in medicine from St John’s College, Cambridge, during which he rowed in the University Boat Race on two occasions and won a silver medal for Great Britain at the 1948 London Olympics at the age of 18. His Olympic connection continued when he was appointed medical officer to the British Olympic team for both the Tokyo …
Is Colchicine Effective Therapy for Cirrhosis?
Authors: James L. Boyer, David F. Ransohoff
Journal: New England Journal of Medicine (1988)

Cirrhosis of the liver is a leading cause of death in the United States and a major worldwide health problem.1 The World Health Organization has estimated that the annual death rate from cirrhosis in some nations is as high as 40 persons per 100,000 population.2 Most cases result from chronic viral infection or the excessive use of alcohol, although toxins, drug reactions, immunologic diseases, and certain rare genetic disorders all contribute. Once the complications of cirrhosis develop (ascites, progressive jaundice, encephalopathy, and hemorrhage from esophageal varices), overall survival rates decline rapidly and are usually below 20 percent within five years. . . .
Ethical and Policy Issues in the Procurement of Cadaver Organs for Transplantation
Authors: Arthur L. Caplan
Journal: New England Journal of Medicine (1984)

IN the past few years there has been a dramatic rise in the demand for organs for transplantation. Advances in surgical techniques, tissue typing, and the development of powerful immunosuppressive drugs, such as cyclosporine, has made it possible to transplant both a larger number and an increasing variety of organs. Among organs and tissues currently being transplanted from cadavers are kidneys, hearts, lungs, livers, bone marrow, skin, corneas, and pancreases.Although some of these procedures are still experimental, graft and recipient survival rates for transplantations have shown steady improvement during the past decade.1 , 2 Many centers report five-year graft survival rates . . .
In-use Evaluation of Safety to Skin of Enzyme-Containing Washing Products
Authors: R. M. Bolam, R. Hepworth, L. T. Bowerman
Journal: BMJ (1971)

The effect on the skin of housewives of using a washing product in the home for all cleaning purposes under conditions of maximal exposure has been studied. Tests conducted on over 4,000 housewives showed that detergents containing proteolytic enzymes had no greater effect on the skin than conventional detergents, even when the hand skin condition was initially poor. The same was true in a further test on 130 housewives with "dishpan" hands. No adverse reactions attributable specifically to the enzyme products were seen. No eruptions from contact with clothes washed in enzyme products were reported from any of the families involved in these tests.