tbuckley/cabot-search huggingface dataset:
Abstract 4573: A novel bispecific Fap-Dr5 antibody inducing potent and tumor-specific death receptor 5 (Dr5) activation by fibroblast activation protein (Fap)-dependent crosslinking
Authors: Katharina Wartha, Barbara Weiser, Thomas Friess, Meher Majety, Valeria Runza, Frank Herting, Thomas Weber, Werner Scheuer, Suzana Vega Harring, Hadassah Sade, Huifeng Niu, Peter Bruenker
Journal: Cancer Research (2014)

Abstract Background: Activation of the extrinsic apoptosis pathway in tumor cells through agonistic death receptor 5 (DR5) antibodies has been evaluated in the clinic with limited success so far. In this context, several reports show that DR5 activation is strongly dependent on receptor hyperclustering on the cell surface. Therefore a therapeutic principle that induces DR5 hyperclustering specifically at the tumor site may provide superior efficacy, potency and safety compared to conventional DR5 agonistic antibodies. Fibroblast activation protein (FAP) is a marker for activated fibroblasts and abundantly expressed in cancer associated fibroblasts of various epithelial tumor indications and as a tumor antigen on tumors of mesenchymal origin. Due to its relative absence from normal tissues, FAP can be used as a tumor targeting antigen. Here, we are using the broad expression of FAP in tumor stroma for crosslinking of DR5 by a bispecific antibody. Aim: In order to achieve superior tumor targeting and tumor located DR5 hyperclustering we have generated a bispecific antibody, RG7386, comprised of an agonistic DR5 binder and a FAP targeting moiety. Results: RG7386 shows potent and selective binding to FAP and DR5 and can simultaneously bind to both targets. In in vitro co-culture assays, using human DLD-1 colon cancer cells and FAP expressing fibroblasts, RG7386 induces potent, FAP dependent DR5 hyperclustering and apoptosis induction in DR5 positive tumor cells (IC50: 0.05 nM). In preclinical in vivo models with co-injection of DLD-1 tumor cells and fibroblasts as well as patient-derived colorectal cancer models, RG7386 shows FAP dependent efficacy and apoptosis induction superior to conventional DR5 antibodies. Furthermore the superior induction of apoptosis could be confirmed by in vivo and ex vivo analysis of cleaved Caspase-3 with imaging, Luminex and histopathology. Conclusion: RG7386 is a promising novel therapeutic entity for the treatment of solid tumors with FAP positive tumor stroma inducing DR5 activation by FAP dependent DR5 hypercrosslinking which results in potent anti-tumor activity. Citation Format: Katharina Wartha, Barbara Weiser, Thomas Friess, Meher Majety, Valeria Runza, Frank Herting, Thomas Weber, Werner Scheuer, Suzana Vega Harring, Hadassah Sade, Huifeng Niu, Peter Bruenker. A novel bispecific Fap-Dr5 antibody inducing potent and tumor-specific death receptor 5 (Dr5) activation by fibroblast activation protein (Fap)-dependent crosslinking. [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 4573. doi:10.1158/1538-7445.AM2014-4573
Furosemide Abuse Without Apparent Adverse Effect
Authors: Elliot J. Howard
Journal: JAMA (1976)

To the Editor.—  A 36-year-old woman, physically healthy but with a neurotic compulsion to lose weight, surreptitiously obtains and takes furosemide (Lasix) in doses of 1,200 to 1,600 mg daily for periods of several weeks. She has done this regularly over the past three years. The patient has submitted to regular examinations and blood and urine studies and admits to gross neurotic behavior, but is unable to discontinue use of the drug. All sorts of attempts to stop her have been futile.  There is no evidence of renal dysfunction or major clinical malady other than a general fatigue or malaise. Occasionally the potassium and chloride levels have fallen below normal, and carbon dioxide levels rise above the normal, but they are easily corrected in the hospital. Glucose and uric acid levels are occasionally elevated, but more often are normal. The calcium content has not been altered. The blood urea nitrogen
Medical Usage and Abusage: "Prevalence" and "Incidence"
Authors: GARY D. FRIEDMAN
Journal: Annals of Internal Medicine (1976)

In view of the frequent misuse of the term "incidence," the concepts of incidence, prevalence, and period prevalence are defined and illustrated. The importance of restricting "incidence" to the rate of development of new events in a population or a group of patients, per unit of time, is stressed. Clearly distinguishing incidence from prevalence or simple proportion can help both in the understanding and the communication of findings in patient groups.
Changes in Plasma Levels of 17-Hydroxycorticosteroids During the Intravenous Administration of ACTH. I. A Test Of Adrenocortical Capacity in the Human1
Authors: Kristen Eik-Nes, Avery A. Sandberg, Don H. Nelson, Frank H. Tyler, Leo T. Samuels
Journal: Journal of Clinical Investigation (1954)

The recognition of the important role played by the adrenal cortex in normal physiology and its significance in withstanding "stressful situations" has led to the development of many tests to meas- ure its functional state and capacity in the human.Most of these tests rely on measurements of phe- nomena which are dependent on the effect of adrenocortical secretions on some special meta- bolic process, and do not involve the direct measurement of adrenocortical steroids.The frequent discrepancies between the clinical picture and these indirect tests indicate that they are not always re- liable indices of adrenal function.Recently, Thorn, Goetz, Streeten, Dingman, and Arons (1) have devised a test for the quantitative estimation of adrenal function based on the deter- mination of butanol-soluble 17,21-dihydroxy-20ketosteroids in the urine.Adrenal capacity is esti- mated by the increase in urinary excretion of these compounds after intravenous administra- tion of adrenocorticotrophic hormone (ACTH).While this technique is a considerable improve- ment over the indirect methods, measurements based on the urine have several disadvantages.If adrenal function or capacity must be determined
Spontaneous gas gangrene in malignant lymphoma: An underreported complication?
Authors: Julio García‐Suárez, Dunia de Miguel, Isabel Krsnik, Mohammed Barr‐Alí, Nuria Hernanz, Carmen Burgaleta
Journal: American Journal of Hematology (2002)

Abstract We report a case of spontaneous gas gangrene (SGG), the most rapidly progressive form of clostridial infection, in a patient with non‐Hodgkin's lymphoma (NHL). We review the literature and examine the association between these two entities. A 43‐year‐old man with NHL developed fatal C. perfringens ‐associated SGG and massive hemolysis during induction chemotherapy. Although patients with NHL usually have several risk factors of SGG, such as bowel involvement or neutropenia, only two cases have been described previously in detail. Common features of all reports are a delayed diagnosis and a fatal outcome. Awareness of this condition should result in prompt antibiotic therapy at the onset of typical presenting symptoms in any lymphoma patient, especially if risk factors are present. Am. J. Hematol. 70:145–148, 2002.© 2002 Wiley‐Liss, Inc.
A study of acute respiratory disease in families exposed to different levels of Air pollution in the Great Salt Lake basin, Utah, 1971-1972 and 1972-1973.
Authors: G J Love, S P Lan, C M Shy
Journal: Environmental Health Perspectives (1982)

The reported incidence of acute respiratory illness in families exposed to different concentrations of air pollution was studied during two consecutive school years. The purpose of the study was to determine the effect of increased exposure to sulfur dioxide and suspended particulate matter. In each of four study communities, the mothers of approximately 250 white families were contacted biweekly to obtain information regarding the occurrence of respiratory symptoms in each family member. Annual mean ambient sulfur dioxide concentrations in one community for the three years included in the study (1971-1973) were well above the current air quality standard of 80 micrograms/m3, while in the other three communities the annual sulfur dioxide concentrations were much lower (usually less than 40 micrograms/m3). Suspended particulate matter concentrations in high sulfur dioxide community were close to the limit designated by the annual standard (75 micrograms/m3) but actual exposures in the four communities probably were not excessive. Regression analyses of the data collected showed inconsistent associations between illness rates and educational attainment of the head of household, crowding in the home, bronchitis in parents or smoking of parents. However, once the effects of these factors were removed the adjusted rates showed little association with community of residence. It was concluded that the higher concentrations of sulfur dioxide in the Utah atmosphere could not be the cause of increases in acute respiratory illness in the exposed populations.
CHARACTER IN YOUNG DELINQUENTS: AN APPROACH FROM THE CRIMINAL GANG ASPECT
Authors: H. T. P. Young
Journal: BMJ (1933)

CRIMINALsignificance of group membership.Experience also shows, GANG ASPECT * however, that, as a result of treatment, where the greater BY rigidity of the rules and conventions of a small group has been found to be particularly suited to the lad's attaiin-H.T. P
Osteoarthritis of weight bearing joints of lower limbs in former elite male athletes
Authors: U M Kujala, J Kaprio, S Sarno
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b> : To compare the cumulative 21 year incidence of admission to hospital for osteoarthritis of the hip, knee, and ankle in former elite athletes and control subjects. <b>Design</b> : National population based study. <b>Setting</b> : Finland. <b>Subjects</b> : 2049 male athletes who had represented Finland in international events during 1920-65 and 1403 controls who had been classified healthy at the age of 20. <b>Main outcome measures</b> : Hospital admissions for osteoarthritis of the hip, knee, and ankle joints identified from the national hospital discharge registry between 1970 and 1990. <b>Results</b> : Athletes doing endurance sports, mixed sports, and power sports all had higher incidences of admission to hospital for osteoarthritis than controls. Age adjusted odds ratios compared with controls were 1.73 (95% confidence interval 0.99 to 3.01, P = 0.063) in endurance, 1.90 (1.24 to 2.92, P = 0.003) in mixed sports athletes, and 2.17 (1.41 to 3.32, P = 0.0003) in power sports athletes. The mean age at first admission to hospital was higher in endurance athletes (70.6) than in other groups (58.2 in mixed sports, 61.9 in power sports, and 61.2 in controls). Among the 2046 respondents to a questionnaire in 1985, the odds ratios for admission to hospital were similar in all three groups after adjusting for age, occupation, and body mass index at 20 (2.37, 2.42, 2.68). <b>Conclusions</b> : Athletes from all types of competitive sports are at slightly increased risk of requiring hospital care because of osteoarthritis of the hip, knee, or ankle. Mixed sports and power sports lead to increased admissions for premature osteoarthritis, but in endurance athletes the admissions are at an older age.
No relationship between gastric pH, small bowel bacterial colonisation, and diarrhoea in HIV-1 infected patients
Authors: C M Wilcox, K B Waites, P D Smith
Journal: Gut (1999)

Conclusive studies of small bowel bacterial overgrowth in patients with HIV-1 infection are limited. The relation was therefore determined between the quantity and species of bacteria in the proximal small intestine of HIV-1 infected patients and the presence of diarrhoea, gastric acidity, severity of immune deficiency, and clinical outcome.Bacteria in the duodenal fluids obtained endoscopically from 32 HIV-1 infected patients, 21 of whom had diarrhoea, and seven control subjects without HIV-1 risk factors were quantified and speciated. Gastric pH was determined at the time of endoscopy. Clinical follow up was performed to assess outcome.Oropharyngeal Gram positive cocci were present in fluids from 28 patients (88%). Gram negative aerobic or facultatively anaerobic bacteria were present in fluids from 12 patients (38%), and strict anaerobes were detected in six patients (19%), but for both groups colony counts infrequently exceeded 10(4) colony forming units/ml. The number and species of bacteria did not correlate with the presence of diarrhoea, gastric pH, or CD4 lymphocyte count.Small bowel bacterial overgrowth is not common in HIV-1 infected patients, regardless of the presence of diarrhoea, and is not associated with hypochlorhydria
An influential doctor: Doctors should be walking question marks
Authors: I. D Conacher
Journal: BMJ (1997)

He is dead now. He looked close to it the few times I saw him 30 years ago. A small, wizened man, rendered kyphotic with age. Besuited, but dapper and with spit and polish black shoes, overlarge for his diminutive frame, he conducted his ward rounds slowly and methodically. He was a consultant in a small hospital, and there was just him, the ward sister, a houseman, and me, the medical student. And yet if I had to put …
Adherence to medication according to sex and age in the CHARM programme
Authors: Bradi B. Granger, Inger Ekman, Christopher B. Granger, Jan Ostergren, Bertil Olofsson, Eric Michelson, John J.V. McMurray, Salim Yusuf, Marc A. Pfeffer, Karl Swedberg
Journal: European Journal of Heart Failure (2009)
Points from Letters: Onycholysis and Enzyme Detergents
Authors: H. R. Vickers
Journal: BMJ (1971)

dialysate,l is recommended routinely for all chronically dialysed patients.It is suggested that the patient under this treatment can not only substitute iron, folate, and amino-acid losses from the remaining blood into the dialyser, blood sampling for analysis, and to the dialysate, but also effectively utilize these elements incorporated in the diet, according to his real needs.-Weare, etc.,
NADPH Oxidases in Johnson Grass Extract (JGE) Induce Intracellular ROS (iROS) in Bronchial Epithelial Cells
Authors: D.R. Redding, M.C. Saavedra, J.G. Patel, N. Dharajiya, I. Boldogh, S. Sur
Journal: Journal of Allergy and Clinical Immunology (2007)
Radiation Therapy for Skin Cancer. Armand B.Cognetta, William M.Mendenhall, eds. New York, NY: Springer, 2013; 251 pp. ISBN: 978-1-4614-6985-8. Price £100·50.
Authors: C. Pembroke
Journal: British Journal of Dermatology (2014)

Journal Article Radiation Therapy for Skin Cancer. Armand B. Cognetta, William M. Mendenhall, eds. New York, NY: Springer, 2013; 251 pp. ISBN: 978‐1‐4614‐6985‐8. Price £100·50. Get access C. Pembroke C. Pembroke Velindre Cancer Centre Velindre Road Whitchurch Cardiff CF14 2TL U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 6, 1 December 2014, Page 1607, https://doi.org/10.1111/bjd.13331 Published: 01 December 2014
Hypotrichosis associated with capillary malformation-arteriovenous malformation syndrome
Authors: A. Martín-Santiago, N. Knöpfel, J. del Pozo, J. Escalas, B. Bartolomé, V. Janer, M. Pascual, C. Nieto, J.A. Hervás
Journal: British Journal of Dermatology (2014)

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is associated with multifocal small CMs and a high risk for high-flow lesions. It is an autosomal dominant disorder, caused by RASA1 gene mutations. Recently, two novel clinical features have been identified: numerous small pale halos with central punctate red spots, and naevus anemicus.To identify the prevalence of the new clinical manifestations in our patients with CM-AVM. The secondary objective was to investigate the presence of other skin lesions.We retrospectively searched the picture database of our department for cases with a clinical diagnosis of CM-AVM, based on the identification of multiple cutaneous CMs and a negative history of epistaxis. We prospectively conducted a clinical and dermoscopic skin examination in all of these patients.Seven patients with multiple CMs were found, and only in one case was a cutaneous AVM present. Five patients had red punctate spots surrounded by pale halos on the upper limbs. Two adult patients also showed multiple telangiectasias on the neck and upper trunk. Naevus anemicus was not detected in any patient. A partial or total absence of vellous hair on the surface of CMs was observed in all patients.Red punctate spots with pale halos or small telangiectasias are frequent findings in CM-AVM syndrome. Hypotrichosis on the CMs suggests that RASA1 gene mutations could be involved in the hair follicle proliferation and cell cycle.
The Safety of Aspartame-Reply
Authors: William M. Pardridge
Journal: JAMA (1987)

<h3>In Reply.—</h3> Drs Levy and Waisbren abandon the linear relationship between the IQ of offspring and maternal plasma phenylalanine concentration that they previously reported<sup>1</sup>; this relationship was significant (<i>r</i>= -.82;<i>P</i>&lt;.001). However, other authors<sup>2</sup>have analyzed these data by linear regression to demonstrate the 10.5-point drop in IQ of the baby for each 250-μmol/L increment in maternal blood phenylalanine level. The issue of whether these data demonstrate that the deleterious effects on brain function caused by hyperphenylalaninemia follow a linear or threshold pattern is as yet unsettled. The fundamental question is whether plasma concentrations on the order of 200 μmol/L have harmful effects on the human central nervous system. This is important now because normal people may achieve this concentration of blood phenylalanine through excessive ingestion of aspartame. Drs Levy and Waisbren indicate that the intake of 10 mg/kg of aspartame products represents "ingestion of large amounts
<b> Altered Expression of ADAMs ( <i>A D</i> isintegrin <i>A</i> nd <i>M</i> etalloproteinase) in Fibrillating Human Atria </b>
Authors: Marco Arndt, Uwe Lendeckel, Christoph Röcken, Karen Nepple, Carmen Wolke, Antje Spiess, Christof Huth, Siegfried Ansorge, Helmut U. Klein, Andreas Goette
Journal: Circulation (2002)

Background — ADAMs ( A D isintegrin A nd M etalloproteinase) are ectoproteases that have recently been reported to be expressed in cardiac tissue. Although they are known to regulate cell-cell and cell-matrix interactions, their pathophysiological role in various cardiac diseases is unclear. The purpose of the present study was to determine whether structural remodeling of the atria during atrial fibrillation (AF) is associated with altered ADAM expression. Methods and Results — Atrial tissue samples of 30 patients undergoing open-heart surgery were examined. Fifteen patients had persistent AF (≥6 months), and the remaining 15 patients had no history of AF. ADAM9, ADAM10, and ADAM15 expression was analyzed quantitatively at the mRNA and protein levels. ADAM expression was localized by immunohistochemistry. ADAM expression was correlated with amounts of integrins β 1 and β 3 . The amount of ADAM10 protein more than doubled during AF (82±15 versus 36±8 U; P &lt;0.01). Amounts of ADAM15 protein (102±12 versus 40±6 U; P &lt;0.01) and mRNA (24.0±5.6 versus 10.5±2.5 U; P &lt;0.05) increased significantly during AF compared with sinus rhythm. ADAM9 protein was not detected in any sample. ADAM/integrin ratios showed an increase of 4- to 6-fold ( P &lt;0.05) in patients with AF who had significantly dilated atria (4.94±0.6 versus 4.3±0.7 cm; P &lt;0.05). ADAM/integrin ratios correlated with atrial diameter. Conclusions — AF is associated with an increase in the expression of ADAM10 and ADAM15. Enhanced ADAM-dependent disintegrin and metalloproteinase activity may be a molecular mechanism that contributes to the dilation of fibrillating human atria.
Surgery of violence. VI. Gunshot wounds of the limbs.
Authors: R H Livingstone, R I Wilson
Journal: BMJ (1975)

Finally, there are hospitals such as the Henderson in Sutton, Surrey, which specialize in the treatment of people with per- sonality disorders who can be either offenders or non-offenders.The principles and philosophy of the therapeutic community obtain.The administration is permissive.Decision making is shared between staff and patients with a view to making the latter assume some responsibility for shaping the world around them.Some measure of success is claimed.The least that can be said for these hospitals is that they are prepared to go on trying.Freud, or whoever it was, claimed to be able to cure the abnormal "normal" man.Would that he had left us some clue to how to cure the normal "abnormal" man.
Institute of Medicine, Congress Seek Solutions to FDA's Safety Woes Through Reform, Funding
Authors: Joel B. Finkelstein
Journal: JNCI Journal of the National Cancer Institute (2007)

An Institute of Medicine report has identified gaping holes in the ability of the U.S. Food and Drug Administration to ensure the safety of new drugs, but experts say the proposals don’t solve possibly the biggest obstacle to safer drugs: inadequate funding. The IOM’s Committee on the Assessment of the U.S. Drug Safety System released their preliminary fi ndings in September, after a series of public meetings held over 15 months. The report contains recommendations for reforming the center within FDA that is responsible primarily for both drug approval and postmarketing safety monitoring. “Underlying our 25 recommendations is the fundamental view that the interests of the public are best served when safety and effi cacy are considered together. However, factors including, but not limited to, the current organizational culture of the Center for Drug Evaluation and Research (CDER), combined with severe resource constraints and a problematic funding mechanism, have impeded the development of a system that optimally integrates the safety and effi cacy assessments along a drug’s life cycle, particularly with regard to safety issues arising postmarketing,” the committee states in the report. Another factor is a lack of consistent leadership at the top of the agency, ac cording to the committee’s chair, Sheila Burke, R.N. “The committee believes that turnover and instability in the commissioner’s offi ce leave the agency without effective leadership or the potential to emphasize safety as having high priority in the work of the agency,” she testifi ed before the Senate Health, Education, Labor, and Pension Committee in November. The Senate re cently confi rmed former National Cancer Institute chief Andrew von Eschenbach, M.D., as FDA’s permanent director. He has been acting head of the agency since September 2005 when Lester Crawford, D.V.M., stepped down 2 months after being confi rmed. “Without stable leadership strongly and visibly committed to drug safety, all other efforts to improve the effectiveness of the agency or position it effectively for the future will be seriously, if not fatally, compromised,” she continued. The report recommends that the center
Structure and functional interaction of the extracellular domain of human GABAB receptor GBR2
Authors: Yong Geng, Dazhi Xiong, Lidia Mosyak, David L Malito, Julie Kniazeff, Yan Chen, Svetlana Burmakina, Matthias Quick, Martin Bush, Jonathan A Javitch, Jean-Philippe Pin, Qing R Fan
Journal: Nature Neuroscience (2012)