tbuckley/cabot-search huggingface dataset:
Potential withdrawal of bevacizumab for the treatment of breast cancer
Authors: A. Jones, P. Ellis
Journal: BMJ (2011)

Calls into question the approval of drugs based on surrogate outcomes

On 29 June the oncology drugs advisory committee of the US Food and Drug Administration (FDA) voted unanimously to recommend withdrawing approval of bevacizumab for the treatment of metastatic breast cancer. The panel concluded that bevacizumab (Avastin, Genentech) is neither effective nor safe for the treatment of breast cancer, and the Food and Drug Administration invited public comment on the decision until 28 July before issuing a final ruling. Why has this happened and what implications does it have for the approval and passage of other new cancer drugs into everyday practice?

The success of targeted treatments such as trastuzumab for HER2 positive breast cancer has given rise to the potential for personalised medicine. It is hoped that our understanding of cancer biology and the ability to develop highly specific drugs for molecular targets will generate targeted treatments for individual cancers that result in improved survival combined with less toxicity. Bevacizumab is a humanised monoclonal antibody that inhibits vascular endothelial growth factor A, which is important in stimulating neoangiogenesis in cancer. The efficacy and safety of this drug in patients with first line metastatic breast cancer were shown in a multicentre randomised trial (E2100), which randomised women with metastatic breast cancer to conventional chemotherapy (paclitaxel) alone or in combination with bevacizumab. …
The role of COX-2 in mediating the effect of PTEN on BMP9 induced osteogenic differentiation in mouse embryonic fibroblasts
Authors: Jun Huang, Shuang-Xue Yuan, Dong-Xu Wang, Qiu-Xiang Wu, Xing Wang, Chang-Jun Pi, Xiang Zou, Liang Chen, Liang-Jun Ying, Ke Wu, Jun-Qing Yang, Wen-Juan Sun, Zhong-Liang Deng, Bai-Cheng He
Journal: Biomaterials (2014)
Surgical Therapy for Coronary Artery Disease Among Patients With Combined Coronary Artery and Peripheral Vascular Disease
Authors: Charanjit S. Rihal, Kim A. Eagle, Mary C. Mickel, Eric D. Foster, George Sopko, Bernard J. Gersh
Journal: Circulation (1995)

Among patients with combined coronary artery and peripheral vascular disease, long-term benefits of surgical therapy compared with medical therapy for coronary artery disease are unknown.Using prospectively collected data from the Coronary Artery Surgery Study registry, we performed a retrospective cohort analysis of 1834 patients (mean age, 56 years; 20% women) with both coronary artery and peripheral vascular disease and evaluated their long-term outcomes. Of these patients, 986 received (nonrandomly) coronary artery bypass graft surgery, and 848 were treated medically. Perioperative mortality was 4.2% (2.9% in the absence of peripheral vascular disease; P = .02). In a mean follow-up period of 10.4 years, 1100 deaths occurred (80% due to cardiovascular causes). For the surgical group, 4-, 8-, 12-, and 16-year estimated probabilities of survival were 88%, 72%, 55%, and 41%, respectively, and 73%, 57%, 44%, and 34%, respectively, for the medical group (P < .0001). Multivariate analysis demonstrated that type of therapy was independently associated with survival (P = .0001; chi 2 = 15.34). Subgroup analysis suggested that benefits of surgical treatment on survival were limited to patients with three-vessel coronary artery disease and were inversely related to ejection fraction. Survival free of death or myocardial infarction was also significantly better among the surgical group. Type of therapy was significantly associated with occurrence of late events (P = .01; chi 2 = 6.55). Subgroup analysis again demonstrated that beneficial effects of surgery were limited to patients with three-vessel coronary artery disease and were inversely related to ejection fraction.Surgical treatment provides long-term benefit for certain subgroups of patients with combined coronary artery and peripheral arterial vascular disease.
Immunodeficiency in Female Sexual Partners of Men with the Acquired Immunodeficiency Syndrome
Authors: Carol Harris, Catherine Butkus Small, Robert S. Klein, Gerald H. Friedland, Bernice Moll, Eugene E. Emeson, Ilya Spigland, Neal H. Steigbigel
Journal: New England Journal of Medicine (1983)

Because the current outbreak of acquired immunodeficiency syndrome (AIDS) among previously healthy adults may be caused by a transmissible biologic agent, and because it may be preceded by immunologic abnormalities with or without a prodromal illness, we studied seven female sexual partners of male patients with the syndrome. The male patients were all drug abusers. One of the seven women was found to have the full-blown syndrome, a second had an illness consistent with the prodrome of AIDS (generalized lymphadenopathy, lymphopenia, and a decreased ratio of helper to suppressor T cells), and four others had generalized lymphadenopathy or lymphopenia, with or without a decreased ratio of helper to suppressor T cells. Only one woman had no abnormalities. These findings suggest that AIDS may be transmitted between heterosexual men and women.
In vitro tumor necrosis factor cytotoxicity in HEP G2 liver cells
Authors: Daniell B. Hill, Jack Schmidt, Steven I. Shedlofsky, Donald A. Cohen, Craig J. McClain
Journal: Hepatology (1995)

Tumor necrosis factor-alpha (TNF-alpha) is a mediator of liver injury. The objective of this study was to develop an in vitro model of TNF-mediated liver cell injury using the Hep G2 cell line. Hep G2 cells normally are insensitive to TNF cytotoxicity, but they were rendered susceptible, or sensitized, to TNF cytotoxicity by inhibitors of RNA and protein synthesis. The concentration of TNF required to kill 50% of Hep G2 cells sensitized with 0.8 mumol/L actinomycin D (Act D) was 35 pmol/L compared with 5 pmol/L for LM fibroblasts, a classic target cell used in TNF cytotoxicity bioassays. Similarly, TNF cytotoxicity occurred in Hep G2 cells sensitized with cycloheximide (CHX), and cytotoxicity to both inhibitors was dose dependent. Both protein and RNA synthesis were inhibited in Hep G2 cells by the concentrations of CHX and Act D associated with TNF cytotoxicity. Hep G2 cells pretreated with TNF alone and later exposed to normally toxic concentrations of TNF with DACT did not develop cytotoxicity. Thus, in vitro tolerance to TNF was induced. Cytotoxicity also was more severe at modestly increased temperatures (39 degrees C versus 37 degrees C), which may have clinical relevance to hepatic decompensation during febrile episodes. We suggest that the Hep G2 cell line sensitized by inhibiting RNA and protein synthesis is a useful in vitro model for evaluating mechanism(s) of TNF-mediated liver cell injury.
Changes in lifestyle reduce breast cancer risk, model shows
Authors: S. Mayor
Journal: BMJ (2011)

Changes in alcohol consumption, physical activity, and body mass index (BMI) reduce the absolute risk of breast cancer by a small but significant amount, a new modelling study has shown.

To estimate the risk of breast cancer the researchers used data from a case-control study of women in Italy (2569 cases and 2588 controls) conducted from 1991 to 1994, together with incidence and mortality data from registries.

They then used these figures to develop a model to predict the absolute risk of breast cancer on the basis of three modifiable risk factors: alcohol consumption, leisure time physical activity, and body mass index. They also included five non-modifiable risk factors: reproductive characteristics, education, occupation, family history, and biopsy history.

Their results showed that the lowest risk lifestyle profile—never drinking alcohol, exercising for at least two hours a week, and maintaining a BMI of <25 after the age …
Long-Term Postoperative Follow-Up in Surgery for Congenital Aortic Valvular Stenosis
Authors: NORMAN B. THOMSON, FRANK C. FISHER
Journal: Circulation (1965)

Twenty-three children with congenital aortic valvular stenosis have undergone operation prior to November 1964, without a hospital mortality. A 4-week-old infant who died at the induction of anesthesia is not included. There was one late death due to uncontrolled aortic regurgitation. The late death occurred at the time of the second operation for placement of aortic valve prosthesis in another institution. Thirteen of the 23 patients have an audible postoperative diastolic murmur. In two this murmur was present preoperatively. Eight of the 13 are considered to have mild aortic regurgitation, four moderate, and one severe. Of the 18 patients with competent valves or mild regurgitation, all have normal electrocardiograms. Ten of these 18 patients had electrocardiographic evidence of left ventricular hypertrophy before surgery. Four of the five patients with moderate or severe regurgitation have electrocardiographic evidence of left ventricular hypertrophy. These patients have all been followed from 3 to 5½ years. There is no evidence that the amount of regurgitation has either decreased or increased since surgery. The gradients measured at cardiac catheterization before operation range from 138 to 56 mm. Hg, with an average of 89 mm. Postoperatively, these gradients ranged from 45 to zero, with an average of 27. Pressures measured at the time of operation before and after valvulotomy agree favorably with the pressures measured at the time of cardiac catheterization before and after valvulotomy. The development of postoperative regurgitation was found to be related to the incision of a rudimentary raphe which made an anatomically bicuspid valve tricuspid. It is also related to the position of the patient in the series, the regurgitation occurring most frequently in the first half of the series. Comparison with another series with a high residual gradient, but a lower incidence of the severity of regurgitation, suggests that the optimal gradient reduction may be purchased at the expense of an unavoidable amount of aortic regurgitation. This aortic regurgitation, however, is not necessarily hemodynamically significant.
Hypermetabolism in Bilateral Basal Ganglia in Sydenham Chorea on F-18 FDG PET-CT
Authors: Linh Ho
Journal: Clinical Nuclear Medicine (2009)

This is an 11-year-old girl with newly diagnosed Sydenham chorea. The patient presented with mood change for 6 months, hearing voices for a few weeks, and dysarthria and abnormal movements for a few days before medical attention. She did not have any recent infections, pharyngitis, or strep throat. In addition, she had no significant medical history or family history, especially neurologic disease or movement disorders. On physical examination, she had continuous choreoathetosis of 4 extremities, more prominent on the right. Brain MRI was unremarkable. The PET-CT images demonstrate significantly and symmetrically increased activity in bilateral caudate and putamen, compatible with Sydenham chorea. This case illustrates the characteristic PET findings of rare Sydenham chorea.
Evidence-based, agreed-upon health priorities to remedy the tuberculosis patient's economic disaster
Authors: G. Sotgiu, V. Mauch, G. B. Migliori, A. Benedetti
Journal: European Respiratory Journal (2014)

New literature review of patient costs in tuberculosis reveals the financial burden of the disease http://ow.ly/vBGejRecently, numerous countries have suffered the impact of the worldwide financial crisis [1].Major economic problems have been faced by low and middle income countries; however, even some European Union nations (such as Greece, Spain and Italy) are experiencing the effects of the global crisis [2].Several experts have noted the limited economic resources focused by governments, and international governmental and non-governmental organisations on health systems: dramatic funding reductions for numerous acute and chronic diseases, inability to improve healthcare organisations, incapability to replace personnel leaving their jobs (e.g.migration to a richer country or retirement), and inability to transfer new diagnostic, therapeutic and preventive approaches to daily routine clinical and public health activities.The most relevant outcome of this scenario is the increased burden of some diseases (inaccurate diagnosis and/ or therapy and/or prevention) [3][4][5].The highest risk of a difficult-to-recover picture is associated with increased probability of transmission of infectious diseases.At this point in time it is crucial to develop a strategy of health priorities based on accurately evaluated epidemiological and financial burdens of the most important diseases.Tuberculosis (TB), one of the main global health priorities with about 9 million estimated new cases and 2 million deaths, together with HIV/AIDS and malaria, creates major economic problems in high burden countries and among affected communities [6].Several studies, as well as systematic reviews and metaanalyses, have been carried out on the healthcare burden of TB, including more severe forms of TB such as multidrug-resistant TB (MDR-TB) [7][8][9][10][11][12].The World Health Organization (WHO) and its partners are finalising the latest version of the new post-2015 TB control and elimination strategy, which will be discussed at the World Health Assembly in May 2014 [13,14].With the vision of leaving a TB-free world to future generations (zero deaths, diseases and TB-related suffering) and the goal of putting an end to the global TB epidemic, the new WHO strategy has ambitious targets for 2035 (fig.1): 1) a 95% reduction in TB deaths (compared with 2015); 2) a 90%
Advances Toward an Understanding of Brainstem Gliomas
Authors: Sarah S. Donaldson, Fred Laningham, Paul Graham Fisher
Journal: Journal of Clinical Oncology (2006)

The diagnosis of brainstem glioma was long considered a single entity. However, since the advent of magnetic resonance imaging in the late 1980s, neoplasms within this anatomic region are now recognized to include several tumors of varying behavior and natural history. More recent reports of brainstem tumors include diverse sites such as the cervicomedullary junction, pons, midbrain, or the tectum. Today, these tumors are broadly categorized as either diffuse intrinsic gliomas, most often in the pons, or the nondiffuse brainstem tumors originating at the tectum, focally in the midbrain, dorsal and exophytic to the brainstem, or within the cervicomedullary junction. Although we briefly discuss the nondiffuse tumors, we focus specifically on those diffuse brainstem tumors that regrettably still carry a bleak prognosis.
A NOTE ON THE "NAVEL BUTTON"
Authors: H. Merriman Steele
Journal: JAMA (1923)

To the Editor:  —The general belief of the layman that any protrusion in the umbilical region of a baby is a hernia, we know, of course, to be wrong. A real hernia is rare, and demands, generally, surgical intervention. It is probably well for the baby that parents do take notice of unnatural protrusions; by replacing and retaining, a real hernia may be prevented. My purpose, however, is to speak against the use of wedge-shaped buttons made in any of the numerous forms now common on the market. One needs to think only for a moment to realize that their use defeats the end for which they are intended. It is a simple fact in physics that if it is desired to keep an opening open, a wedge, for instance, inserted and retained will accomplish that end. Why is this reasoning not applicable to the use of a wedge-shaped button
Natural Resistance of Animals to Cancer
Authors: Peter A. Herbut
Journal: JAMA (1961)

THIS PAPER is concerned with an investigation of the innate mechanism of animals against cancer and an attempt to bring together the many theories regarding the causes of this disease. It has been clearly demonstrated that the guinea pig normally possesses in its serum a powerful tumor inhibitory principle (TIP) against a variety of transplantable tumors.<sup>1. 5. 6</sup>In attempting to isolate TIP we determined that it is not contained in erythrocytes or their products, that it is not a lipopolysaccharide, complement, or properdin, and that it is not extractable with dimethylformamide, acetone, or ether.<sup>5</sup>Contrarily, we demonstrated that it is heat stable, that it is extractable with methanol, that it can be separated off by ammonium sulfate fractionation, and that it is associated with the globulin fraction of the serum. Examining physiologic saline extracts and ammonium sulfate fractions of such extracts of guinea pig muscle, lung, spleen,
PROGRESS WITHOUT STATISTICS
Authors: H. M. C. LUYKX
Journal: JAMA (1949)

Among the functions of the Therapeutic Trials Committee is the encouragement of critical controlled clinical trials of new agents in the diagnosis, prevention and treatment of disease. Such trials must be pursued by recognized scientific methods, many of which involve the application of simple statistical procedures. Furthermore, data derived from such clinical trials frequently can best be assembled and presented with the aid of statistical technics. Hence, clinical investigators and readers of scientific journals should be familiar with the uses and limitations of the commonly used statistical methods and the interpretation which may safely be drawn from the results of the statistical treatment of data.  The Committee requested Dr. H. M. C. Luykx of New York University to prepare a general article on this subject. The Committee believes that the methodology of statistics is best left to the statistician but that the need for and interpretation of statistical procedures should
Abstract 4260: Sunitinib treatment induces Notch expression and activation in renal carcinoma cell lines
Authors: Fani Ziouti, Panagiota Touplikioti, Maria-Ekaterini Kontovini, Christina Vadeka, Loukas Kontovinis, Konstantinos Papazisis
Journal: Cancer Research (2011)

Abstract Introduction. Notch signaling is an evolutionary conserved pathway that plays a central role in stem cell biology, tumor formation, angiogenesis and cell fate decisions. Currently there is not any clear view as to whether Notch plays an oncogenic role in renal cell cancer (RCC). Notch-1 is activated after cytotoxic stimuli and may induce mTor pathway activation, leading to increased cell survival. We have investigated the role of Notch expression and activation in RCC cell lines in response to sunitinib treatment and the role of Notch in the activation of the mTor pathway. We elaborated three cell lines with a different VHL and PTEN mutation status: Caki-1 cells (VHL-wt, PTEN-wt), Caki-2 (VHL-mut, PTEN-wt) and 786-O (VHL-mut, PTEN-mut). Results: When Caki-1 and Caki-2 cells were exposed to sunitinib there was a marked upregulation in the expression of the Notch-1 mRNA and the target transcription factors RUNX1, RBPJ and HES1. The PI3K – mTor – S6K pathway was aslo upregulated. This upregulation was reversed when cells were pre-treated with a gamma-secretase inhibitor. However, both gamma secretase inhibitors and everolimus (an m-Tor inhibitor) had an antagonistic effect when combined with sunitinib (Combination Index &amp;gt;&amp;gt; 1.0). On the other hand, PTEN-mutant 786-O cells have a dysregulated mTor pathway and are more sensitive to inhinition of the m-Tor with everolimus. Sunitinib exposure did not result in further increase of the PI3K-mTor-S6K activation. Interestingly, combination of sunitinib with everolimus was synergistic in 786-O. Conclusions: VHL-wt and VHL-mutant RCC cells treated with sunitinib activate the Notch pathway. There are reports that Notch plays a tumor suppressor role in RCC and our results are on concert with that. Furthermore, Notch seems to regulate m-Tor pathway activation in cells with a wild-type PTEN. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4260. doi:10.1158/1538-7445.AM2011-4260
Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery
Authors: Ryan Hutfless, Radmila Kazanegra, Michael Madani, Meenakshi Awasthi Bhalla, Alisi Tulua-Tata, Amelia Chen, Paul Clopton, Cherimarie James, Albert Chiu, Alan S Maisel
Journal: Journal of the American College of Cardiology (2004)
Give and Take
Authors: Thomas E. Starzl
Journal: JAMA (1964)

This slender volume was prepared for lay consumption by the distinguished Moseley Professor of Surgery at Harvard. For this purpose, it is admirably suited, containing a colorfully written and informal account of those experiences in transplantation which have transpired at the Peter Bent Brigham Hospital, Boston, during the past 13 years. An idea of the intent, content, and style of the book can be obtained by perusal of the descriptive chapter titles and subtitles as captioned by the author: (1) "Grafts That Live and Breathe (The Central Problem)"; (2) "Individuality Arouses Antagonism (The Hostile Host)"; (3)"Tolerance, Natural and Acquired (Nature Permits the Impermissible)"; (4) "The Unbreached Barrier (Kidney Transplantation without Immuno-Suppression)"; (5) "Most Kidneys Are Paired, Most People Are Not (The Identical Twin Episode)"; (6) "Battering at the Barrier (Whole Body Irradiation As a Means of Immuno-Suppression)"; (7) Breaching the Barrier (Immuno-Suppression with Drugs)"; (8) "From the Laboratory to the
The cheaper drug, bevacizumab, should be referred to NICE
Authors: James P Raftery, Andrew Lotery
Journal: BMJ (2007)

We think that Chakravarthy and Lim could have said more about the pricing of ranibizumab and bevacizumab.1 Both drugs are owned by a single company, Roche/Genentech, which has no intention of licensing the cheaper. The US price of ranibizumab is $1950 or roughly £1000 per injection. Monthly injections would cost £12 000 per patient. Bevacizumab, which is licensed for cancer treatment, could cost as little as £17 per injection, as the dosages used for eyes are minute compared with cancer. In the US, off-licence bevacizumab is estimated …
Semi-continuous Left Atrial Pressure Measurements during Mitral Valvotomy
Authors: H. Baden
Journal: Thorax (1955)

Several authors have evaluated the immediate results of mitral valvotomies by comparing pressures in the left atrium before and after cutting or fracturing the commissures, but, as far as can be ascertained, few papers give detailed information about the merits of these pressure readings.In an earlier report from this hospital Pedersen and Tybjaerg Hansen (1953) published measure- ments from the left atrium in 15 cases.In 12 cases of valvotomy for mitral stenosis without significant regurgitation a decrease of pressure was recorded in every instance, averaging 11 mm.Hg (range 1-23 mm.Hg).In three cases of pure mitral incompetence, in which only exploration of the atrium was performed, an increase of pressure was re- corded in every instance.Lee, Ordway, and Gerbode (1954) measured left atrial pressure before and after valvotomy in 26 cases and compared the decrease of pressure with the clinical result assessed six weeks to 14 months after the operation.Three patients with an " excellent " result showed an average decrease of left atrial systolic pressure of 15.3 mm.Hg.The corresponding figures for 13 " good " and 11 " poor " results were 10.7 and 2.7 mm. Hg respectively.Thus the average figures seemed a good indicator of the clinical result, but the figures in their tables show so great a variation in each group that the pressure changes in the individual case would be a poor guide to the clinical result.Lev, Connolly, Kirklin, and Wood (1954) used a catheter inserted through the left superior pulmonary vein.In 21 cases the left atrial pressure was measured about 10 and two minutes before, and about two and 20 minutes after, valvotomy.