tbuckley/cabot-search huggingface dataset:
Randomized Phase Ib/II Trial of Rilotumumab or Ganitumab with Panitumumab versus Panitumumab Alone in Patients with Wild-type <i>KRAS</i> Metastatic Colorectal Cancer
Authors: Eric Van Cutsem, Cathy Eng, Elzbieta Nowara, Anna Świeboda-Sadlej, Niall C. Tebbutt, Edith Mitchell, Irina Davidenko, Joe Stephenson, Elena Elez, Hans Prenen, Hongjie Deng, Rui Tang, Ian McCaffery, Kelly S. Oliner, Lisa Chen, Jennifer Gansert, Elwyn Loh, Dominic Smethurst, Josep Tabernero
Journal: Clinical Cancer Research (2014)

Panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody (mAb), has demonstrated efficacy in patients with wild-type KRAS metastatic colorectal cancer (mCRC). Rilotumumab and ganitumab are investigational, fully human mAbs against hepatocyte growth factor (HGF)/scatter factor and IGF1R, respectively. Here we evaluate combining rilotumumab or ganitumab with panitumumab in previously treated patients with wild-type KRAS mCRC.Part 1 was a phase Ib dose-finding study of panitumumab plus rilotumumab. The primary endpoint was the incidence of dose-limiting toxicities (DLT). Part 2 was a randomized phase II trial of panitumumab in combination with rilotumumab, ganitumab, or placebo. The primary endpoint was objective response rate (ORR); safety, progression-free survival (PFS), and overall survival (OS) were secondary endpoints. Archival tissue specimens were collected for exploratory correlative work.In part 1, no DLTs were reported. A recommended phase II dose of 10 mg/kg rilotumumab was selected. In part 2, for the panitumumab plus rilotumumab (n = 48), panitumumab plus ganitumab (n = 46), and panitumumab plus placebo arms (n = 48), the ORRs were 31%, 22%, and 21%, respectively. The median PFS was 5.2, 5.3, and 3.7 months and median OS 13.8, 10.6, and 11.6 months, respectively. Adverse events were tolerable. Exploratory biomarker analyses, including MET and IGF-related protein expression, failed to indicate conclusive predictive evidence on efficacy endpoints.Panitumumab plus rilotumumab met the prespecified criterion for improvement in ORR whereas ganitumab did not. This is the first study to suggest a benefit for combining an HGF inhibitor (rilotumumab) with panitumumab in previously treated patients with wild-type KRAS mCRC.
4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial
Authors: Peter J Hoskin, Amy A Kirkwood, Bilyana Popova, Paul Smith, Martin Robinson, Eve Gallop-Evans, Stewart Coltart, Timothy Illidge, Krishnaswamy Madhavan, Caroline Brammer, Patricia Diez, Andrew Jack, Isabel Syndikus
Journal: The Lancet Oncology (2014)
Japan to test 1m cattle after discovery of first case of BSE
Authors: Joe Lamar
Journal: BMJ (2001)

The Japanese government has announced that it will test 1 million cattle for bovine spongiform encephalopathy (BSE) after the discovery of Asia's first case of mad cow disease. The cows will be tested after they have been slaughtered for meat.

The mass testing, along with a ban on meat and bone feed and the start of new research into Creutzfeldt-Jakob disease, are designed to allay consumer concerns, which have been heightened by a blundered …
Regulatory and Judicial Oversight of Nonprofit Hospitals
Authors: David M. Studdert, Michelle M. Mello, Christopher M. Jedrey, Troyen A. Brennan
Journal: New England Journal of Medicine (2007)

Nonprofit hospitals agree to operate for charitable purposes in exchange for exemption from taxes. As financial pressures facing hospitals have intensified, the business decisions of nonprofit hospitals are being challenged by the Internal Revenue Service, state attorneys general, and patients. Uninsured patients have joined class-action lawsuits arguing that nonprofit hospitals are abandoning their charitable missions and accusing them of overcharging uninsured patients and of using aggressive debt-collection measures when uninsured patients cannot pay their bills.
A Balloon Tipped Catheter for Obtaining His Bundle Electrograms Without Fluoroscopy
Authors: STEVEN G. MEISTER, VIDYA S. BANKA, KUL D. CHADDA, RICHARD H. HELFANT
Journal: Circulation (1974)

A technique for recording His bundle activity in man without fluoroscopic guidance is described. Balloon tipped tri- or tetrapolar catheters were designed with pacing electrodes located at the catheter tip, and two fine sensing electrodes 4 and 5 cm behind it. The catheter tip was preformed into a "J" curve. Following percutaneous transfemoral insertion, the catheter is floated to the right ventricle under electrocardiographic control. This tip configuration and the transfemoral route of insertion typically directs the catheter into an inverted "J" position with its tip in or near the right ventricular apex. Subsequent catheter withdrawal carries the sensing electrodes through the superior portion of the tricuspid valve and permits recording from the His bundle. With this technique His bundle recordings were possible in 23 of 24 patients. Re-advancement into the right ventricular apex permits stable temporary pacing.
Preparedness for humanitarian crises needs to be improved
Authors: Altaf Musani, Irshad Shaikh
Journal: BMJ (2006)

An estimated 4.1 billion people were affected by natural disasters, including earthquakes, floods, landslides, and drought, during 1984-2003.1 Over 160 countries experienced such disasters in 2004, and these, together with industrial incidents such as chemical spills, resulted in over 350 000 deaths.2 One of the most common human generated disasters, however, is conflict.3 In the past decade there have been over 38 major conflicts globally, with 70% of the victims being civilians. The percentage of civilians killed and injured in conflict has been increasing, and is currently around 90%.4

In the World Health Organization's Eastern Mediterranean region, Afghanistan, Iraq, Lebanon, the Occupied Palestinian Territory, Somalia, and Sudan are currently struggling to deal with prolonged conflicts. The United Nations emergency relief coordinator, Jan Egeland, described the conflicts in Somalia, Sudan, and the Occupied Palestinian Territory as the three most challenging current humanitarian situations (box).5 They have affected 10 million people, of whom 6.5 million have been displaced from their homes and around 200 000 have died.6 The long history of ethnic, religious, and geographic tensions in these areas make it unlikely that the health and humanitarian problems are going to decrease.

Poor and marginalised members of society are most often exposed to disasters and least capable of coping when they occur.7 The infrastructure of cities such as Karachi, Lahore, Cairo, Tehran, Sanaa, Kabul, Mogadishu, Hargeisa, Khartoum, and Baghdad can no longer cope with the growing populations. Hundreds of thousands of people live in slums or low income housing. These homes are relatively unsafe because they are of poor structural quality or in high risk locations, which is likely to compound future emergencies.

In 2001 WHO set up a dedicated emergency and humanitarian action unit in Cairo to provide technical and public health expertise and …
Somatic mosaicism in plants with special reference to somatic crossing over
Authors: Baldev K. Vig
Journal: Environmental Health Perspectives (1978)

Plant systems in use for the detection of environmental mutagens appear capable of detecting all types of genetic effects which can be studied in animals. The study of somatic mosaicism, however, is better developed in plants than in higher animals. A case is presented here which shows the ability of plant systems in analyzing a host of genetic end points, including chromosome aberrations like deletions, somatic crossing over, numerical inequality, gene conversion, paramutations and point mutations. The systems in general use utilize certain varieties of Tradescantia, Glycine max, Nicotiana tabacum, Antirrhinum majus, Petunia hybrida, and Arabidopsis thaliana. Heterozygous plants or their homozygous counterparts with gene markers affecting chlorophyll development or anthocyanin in floral parts are exploited in these studies. Mutagens produce different frequencies of different types of spots typical of the mode of action of the agent. Analysis of these parameters may be used to predict, at least qualitatively, the kind of genetic damage that might be produced in man. Besides, one can test the validity of interpretation by traditional progeny tests of plants raised from tissue culture from sectors as in Nicotiana and/or by precursor analysis as done in Antirrhinum. The study of mosaicism in plants offers quite inexpensive, rapid, and reliable tests of mutagenicity at least as a preliminary eukaryotic test system.
Haemophilus influenzae apparently resistant to trimethoprim.
Authors: S R Bushby
Journal: BMJ (1973)

this effect is unknown and findings are the opposite to those on serum corticosteroids in immobilized patients, which are significantly raised.2There may be either reduced testicular response to gonadotrophins or decreased hypothalamus-pituitary gland activity.It would seem that both extremes of physical activity have significant effects on serum androgens in men.-We are, etc.,
A Unique Co-culture Model for Fundamental and Applied Studies of Human Fetoplacental Steroidogenesis and Interference by Environmental Chemicals
Authors: Andrée-Anne Hudon Thibeault, Kathy Deroy, Cathy Vaillancourt, J. Thomas Sanderson
Journal: Environmental Health Perspectives (2014)

Background: Experimental tools for studying the complex steroidogenic interactions that occur between placenta and fetus during human pregnancy are extremely limited.Objectives: We aimed to develop a co-culture model to study steroidogenesis by the human fetoplacental unit and its disruption by exposure to environmental contaminants.Methods: We cultured BeWo human choriocarcinoma cells, representing the villous cytotrophoblast, and H295R human adrenocortical carcinoma cells, representing the fetal unit, in a carefully adapted co-culture medium. We placed H295R cells in 24-well plates and BeWo cells on transwell inserts with or without pesticide treatment (atrazine or prochloraz) and assessed CYP19 activity and hormonal production after 24 hr of co-culture.Results: The co-culture exhibited the steroidogenic profile of the fetoplacental unit, allowing a synergistic production of estradiol and estriol (but not of estrone) of 133.3 ± 11.3 pg/mL and 440.8 ± 44.0 pg/mL, respectively. Atrazine and prochloraz had cell-type specific effects on CYP19 activity and estrogen production in co-culture. Atrazine induced CYP19 activity and estrogen production in H295R cells only, but did not affect overall estrogen production in co-culture, whereas prochloraz inhibited CYP19 activity exclusively in BeWo cells and reduced estrogen production in co-culture by almost 90%. In contrast, prochloraz did not affect estradiol or estrone production in BeWo cells in monoculture. These differential effects underline the relevance of our co-culture approach to model fetoplacental steroidogenesis.Conclusions: The co-culture of H295R and BeWo cells creates a unique in vitro model to reproduce the steroidogenic cooperation between fetus and placenta during pregnancy and can be used to study the endocrine-disrupting effects of environmental chemicals.Citation: Hudon Thibeault AA, Deroy K, Vaillancourt C, Sanderson JT. 2014. A unique co-culture model for fundamental and applied studies of human fetoplacental steroidogenesis and interference by environmental chemicals. Environ Health Perspect 122:371–377; http://dx.doi.org/10.1289/ehp.1307518
A STUDY OF THE ANTIFIBRINOLYSIN ACTIVITY IN HUMAN PLASMAS DURING PATHOLOGICAL STATES 1
Authors: M. Mason Guest, Byrne M. Daly, Arnold G. Ware, Walter H. Seegers
Journal: Journal of Clinical Investigation (1948)

Utilizing the methods described in the preceding report (1), a study of the antifibrinolysin ac- tivity in plasmas from patients of Receiving and Harper Hospitals in the City of Detroit has been initiated.The antifibrinolysin in human plasma which was assayed inactivates bovine fibrinolysin.The results indicate that there is a tendency for the antifibrinolysin activity to be increased in a number of different diseases.The conditions studied include: pneumonias, coronary thrombo- sis, pernicious anemia, secondary anemia, cir- rhosis of the liver, intestinal obstructions and acute bacterial endocarditis.Other pathologies may also result in an increased plasma anti- fibrinolysin activity, although no increase was found in patients convalescing from fractures.EXPERIMENTAL
Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge in cats.
Authors: P A Padrid, P Cozzi, A R Leff
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We determined the effect of cyclosporine A (CSA) on airway reactivity and remodeling after chronic antigen challenge in Ascaris suum (AA)-sensitized cats. CSA efficacy was demonstrated by inhibition of interleukin-2 (IL-2) production from phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear (PBMN) cells. Twenty-four hours after the first AA exposure, cats not receiving cyclosporine (CsA-) demonstrated airway hyperresponsiveness (AHR) to acetycholine (approximately 1.0 log increase in PD200 versus baseline; p < 0.01), and a 13-fold increase in eosinophils in bronchoalveolar lavage fluid (BALF) (p < 0.01). AHR persisted (approximately 1.5 log increase in PD200 p < 0.001 versus baseline), and BALF eosinophilia was unchanged in CsA-cats 72 h after final AA challenge. The percent of normodense BALF eosinophils also decreased substantially in CsA-cats (p < 0.05). Necropsy specimens from CsA-cats demonstrated: (1) increased smooth-muscle thickness; (2) goblet cell and submucosal gland hypertrophy and hyperplasia; and (3) epithelial erosion with eosinophilic infiltration. There was no significant change in AHR, BALF, eosinophilia, or histology after chronic AA challenge in Csa-treated cats. These data suggest that CsA inhibits products of immune cells necessary for the development of AHR, airway inflammation, and airway wall remodeling caused by immune-sensitization in this model of atopic asthma.
Long term propranolol treatment and changes in body weight after myocardial infarction.
Authors: S Rossner, C L Taylor, R P Byington, C D Furberg
Journal: BMJ (1990)

OBJECTIVE--To determine the effect of long term propranolol treatment on body weight. DESIGN--Retrospective analysis of data from a placebo controlled randomised double blind clinical trial (the beta blocker heart attack trial). PATIENTS--3837 Men and women randomised 5-21 days after an acute myocardial infarction to treatment with placebo or propranolol for up to 40 months. Patients were followed up at annual visits. MAIN OUTCOME MEASURE--Changes in body weight. RESULTS--At the first annual visit patients treated with propranolol had gained more weight than those given placebo (mean weight gain 2.3 kg v 1.2 kg respectively, mean difference 1.2 kg (95% confidence interval 0.9 to 1.5]. These group differences remained at the second and third annual visits. The difference in weight gain could not be explained by discrepancies in the use of diuretics or in physical activity and was similar in patients of both sexes and of all ages. CONCLUSION--Long term beta blockade results in a sustained weight gain.
Overview: Progression-Free Survival as an Endpoint in Clinical Trials with Solid Tumors
Authors: Ronald L. Korn, John J. Crowley
Journal: Clinical Cancer Research (2013)

Abstract Progression-free survival (PFS) is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors for both practical and clinical considerations. Although in its simplest form, PFS is the time from randomization to a predefined endpoint, there are many factors that can influence the exact moment of when disease progression is recorded. In this overview, we review the circumstances that can devalue the use of PFS as a primary endpoint and attempt to provide a pathway for a future desired state when PFS will become not just a secondary alternative to overall survival but rather an endpoint of choice. Clin Cancer Res; 19(10); 2607–12. ©2013 AACR.
Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis.
Authors: T Takeuchi, K Amano, H Sekine, J Koide, T Abe
Journal: Journal of Clinical Investigation (1993)

Upregulation of integrin adhesive receptors has been implicated in various pathological conditions. We examined expression and function of integrin adhesive receptors on peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE), particularly those with the complication of vasculitis, and found that VLA-4 and LFA-1 expression was increased in SLE patients with vasculitis, while LFA-1 but not VLA-4 expression was increased in those without vasculitis. These results suggested a role of VLA-4 in the pathogenesis of vasculitis in SLE. Functional studies further demonstrated that adhesion to cytokine-activated human umbilical cord vein endothelial cells and to the CS-1 alternatively spliced domain of fibronectin was significantly increased in SLE patients with vasculitis. Analysis of the functional epitopes on the alpha 4 chain demonstrated that antigen densities of all the functional epitopes were increased in those with vasculitis, indicating that the increased expression of VLA-4 resulted from the increased number of VLA-4 molecules, and was not secondary to an increase in one particular functional epitope. Immunoprecipitation studies further support these results. Interestingly, high molecular weight bands associated with VLA-4 were observed in about half of the SLE patients with vasculitis. These results introduce a possibility that upregulation of integrin adhesive receptors has a potential role in the pathogenesis of vasculitis in SLE.
Sister Kenny: The Woman Who Challenged the Doctors
Authors: Marjorie C. Meehan
Journal: JAMA (1976)

A nurse who, from 1943 to 1951, consistently ranked just after Eleanor Roosevelt as the woman most admired by American women, was at the same time a source of controversy in the medical establishment. Today, her name is seldom mentioned, the emotions she aroused have subsided, and a relatively unbiased biography and evaluation is possible. Victor Cohn has written a fascinating report of this unusual woman. Elizabeth Kenny, born and brought up in rural Australia, probably had no more than six years of formal schooling and no regular nurse's training. After assisting in a small hospital, she set up as a self-appointed nurse in the bush. She worked hard, demanded no regular fees, and consulted with doctors. In 1911 she saw her first poliomyelitis cases. When she telegraphed the symptoms to her favorite doctor, he replied, "Infantile paralysis. No known treatment. Do the best you can with the symptoms presenting
Measuring and knowing. The trouble with cholesterol and decision making
Authors: J. T. Gwynne
Journal: JAMA (1991)

The evidence that lowering serum low-density lipoprotein (LDL) cholesterol levels prevents both primary and recurrent myocardial infarction now seems overwhelming. Two major primary prospective intervention trials, the Lipid Research Primary Prevention Trial 1,2 and the Helsinki Heart Study, 3,4 have shown that lowering total and LDL cholesterol levels will decrease the incidence of fatal and nonfatal myocardial infarctions in high-risk middle age men. The outcome of these trials is quantitatively consistent with less-definitive primary prevention trials employing diet alone and is consistent with the degree of benefit predicted by observational epidemiologic studies relating total cholesterol to coronary artery disease risk. 2,5 Treatment with nicotinic acid as part of the Coronary Drug Project, a secondary prevention trial in middle-aged men, not only decreased the incidence of nonfatal reinfarction 6 but also appeared to have decreased mortality at the 15-year follow-up. 7 The results of recent pharmacologic
The thrifty genotype and non-insulin dependent diabetes.
Authors: R Fox
Journal: BMJ (1993)

An audit of the outcome of these periodic procedures from Germanaud's study would help in decisions regarding starting, continuing, or stopping periodic tuberculin testing or chest x ray examinations, or both, for hospital employees.Evaluation of the British data from occupational health departments in the health service has shown that routine annual chest x ray examination for this group of workers is not justified.4
Measurement of Left Ventricular Diameter In the Dog by Cardiac Catheterization
Authors: RICHARD A. CARLETON, JAMES G. CLARK
Journal: Circulation Research (1968)

A cylindrical ultrasonic transducer on a catheter tip lodged in the cleft between the free wall of the right ventricle and the interventricular septum provides an easily measured echo from the posteroinferior left ventricular epicardial surface. The sonic path represents a diameter of the left ventricle at approximately its largest cross-sectional area. Experiments in six dogs demonstrated that measurements by ultrasound agree within ±6% with simultaneous radiographic measurements of left ventricular diameter. Procedures designed to alter left ventricular volume were employed in 14 dogs to clarify the physiologic meaningfulness of the left ventricular diameter measured by ultrasound. Both end-diastolic and end-systolic diameter increased with anoxia, with sudden injections of saline into the left ventricle, after propranolol, and after inflation of a balloon in the thoracic aorta. These diameters decreased with isoproterenol, with increased heart rate, and after inflation of a balloon in the inferior vena cava. The present technique provides accurate and physiologically meaningful estimates of left ventricular diameter. Ventricular diameter measurements obtained during cardiac catheterization should permit assessment of ventricular distensibility and of ventricular function.
"SHAM RAGE" IN MAN
Authors: HERMAN WORTIS, WILLIAM S. MAURER
Journal: American Journal of Psychiatry (1942)

1. The literature relative to "sham rage" is reviewed. 2. Two cases of "sham rage" in human beings are presented; one following insulin hypoglycemia, the other following carbon monoxide poisoning. In both cases, the involvement of higher centers is stressed, and the resultant "sham rage" is believed to be the result of uninhibited hypothalamic discharge. 3. The expression of emotion does not necessarily mean that the individual is experiencing that emotion. 4. There seems to be no reason for accepting the idea that the hypothalamus is the "emotional center" of the body. Affects and emotions are highly complicated psychosomatic processes, which require among other things a functioning cerebral cortex.
Pharmacokinetic study and metabolite identification of the bidesmosidic triterpenoid saponin BTS-1 in rat plasma
Authors: Jianguang Luo, Chan Zhou, Wei Zhang, Lingyi Kong
Journal: Acta Pharmaceutica Sinica B (2013)

Assays based on high-performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC–MSn) have been developed and validated for the determination and metabolite identification of the bidesmosidic triterpenoid saponin, BTS-1 (3-O-β-d-galactopyranosyl-(1→2)-[β-d-xylopyranosyl-(1→3)]-β-d-glucuronopyranosyl gypsogenin 28-O-α-l-arabinopyranosyl-(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-β-d-fucopyranoside), in rat plasma. The assay was successfully applied to a pharmacokinetic study in rats given a single oral dose of BTS-1 (400 mg/kg). The results indicated that the compound was rapidly absorbed (Tmax=1.28±0.29 h, Cmax=37.4±5.6 µg/mL) and slowly eliminated (t1/2=13.2±6.6 h). In addition, secondary glycosides and aglycones of BTS-1 were detected and identified. Since these metabolites are known to be active α-glucosidase inhibitors, they probably play an important role in mediating the pharmacological effects of the saponin.