tbuckley/cabot-search huggingface dataset:
Management of faecal incontinence in adults
Authors: M. Ahmad, I. J. D. McCallum, M. Mercer-Jones
Journal: BMJ (2010)

#### Summary points

Faecal incontinence is the involuntary loss of stool or flatus. It is a distressing condition that can have a substantially negative effect on quality of life.1 2 According to a systematic review it may affect 11-15% of the population.3 The estimated cost of absorbent products (such as pads) is around £94m (€112m; $138m) per annum in the United Kingdom.4 Because faecal incontinence is a heterogeneous problem that ranges from minor faecal soiling to incapacitating urge or passive faecal incontinence and embarrassment may prevent patients from seeking help, estimates of prevalence may not be accurate. Incontinence is a common reason for admission to residential care even though in many cases simple measures are available in primary care that could enable people to remain at home. We review evidence on causes, diagnosis, and management of faecal incontinence in adults and summarise the findings of systematic reviews and guidelines where possible.

#### Sources and selection criteria

We searched PubMed, National Institute for Health and Clinical Excellence guidelines, Embase, and the Cochrane library using the search terms faecal/fecal incontinence. We retrieved potentially useful studies and critically evaluated them for inclusion.

An epidemiological survey showed a rising incidence with advancing age and the highest prevalence in elderly people in long term care, with no sex difference in adults aged over 40.5 The higher reported prevalence of faecal incontinence in younger women is probably the result of childbirth related injuries, and a prospective study showed that the greatest risk follows the first vaginal …
Miglitol suppresses the postprandial increase in interleukin 6 and enhances active glucagon-like peptide 1 secretion in viscerally obese subjects
Authors: Masayuki Arakawa, Chie Ebato, Tomoya Mita, Yoshio Fujitani, Tomoaki Shimizu, Hirotaka Watada, Ryuzo Kawamori, Takahisa Hirose
Journal: Metabolism (2008)
Expression of Recombination Activating Genes in Germinal Center B Cells: Involvement of Interleukin 7 (IL-7) and the IL-7 Receptor
Authors: Masaki Hikida, Yasunori Nakayama, Yumi Yamashita, Yoshio Kumazawa, Shin-Ichi Nishikawa, Hitoshi Ohmori
Journal: The Journal of Experimental Medicine (1998)

Mouse germinal center (GC) B cells have been shown to undergo secondary V(D)J (V, variable; D, diversity; J, joining) recombination (receptor editing) mediated by the reexpressed products of recombination activating gene (RAG)-1 and RAG-2. We show here that interleukin (IL)-7 as well as IL-4 was effective in inducing functional RAG products in mouse IgD+ B cells activated via CD40 in vitro. Blocking of the IL-7 receptor (IL-7R) by injecting an anti– IL-7R monoclonal antibody resulted in a marked suppression of the reexpression of RAG-2 and subsequent V(D)J recombination in the draining lymph node of immunized mice, whereas RAG-2 expression was not impaired in immunized IL-4–deficient mice. Further, these peripheral B cells activated in vitro or in vivo were found to express IL-7R. These findings indicate a novel role for IL-7 and IL-7R in inducing receptor editing in GC B cells.
Cholelithiasis in Persons Under 25 Years Old
Authors: Dennis B. Goodman
Journal: JAMA (1976)

Ninety-six of 683 patients undergoing cholecystectomy at the Naval Regional Medical Center, Long Beach, Calif, from 1967 to 1974 were between 7 and 25 years old. Although females predominated in ratio of 4:1, the sex incidence was equal when nulliparous females were compared with males. Signs and symptoms were nonspecific in 70%, leading to delay in proper diagnosis in 26%. Only two patients had an underlying blood dyscrasia. Oral cholecystography proved to be the most reliable diagnostic test. Moreover, the incidence of choledocholithiasis was 4.1%, approximately one third less than in older age groups.
Use of simple analgesics in rheumatoid arthritis.
Authors: T Gibson, B Clark
Journal: Annals of the Rheumatic Diseases (1985)

The usefulness of anti-inflammatory drugs in rheumatoid arthritis (RA) is beyond dispute. The role of simple analgesics is less clear and has been disputed. A survey of 21 rheumatologists indicated that a majority sometimes supplemented anti-inflammatory treatment of RA with simple analgesics. A random sample of 120 RA patients treated by the same doctors revealed that 47% ranked pain relief as the most desirable objective of their treatment and 54% were taking analgesics regularly. Of those receiving analgesics as well as non-steroidal anti-inflammatory drugs 48% considered the former to be the more effective preparations. Almost half the patients on analgesics were taking drugs without the knowledge of the rheumatologists, who may have underestimated their patients' desire for pain relief.
The argument for helmets.
Authors: C. Illingworth
Journal: BMJ (1992)

went to war over petroleum.Yet, ifin the 1960s, 1970s, and 1980s we have come to recognise the dangers of addiction to cigarettes, drugs, and alcohol and begun to seek to reduce their use, in the 1990s we must acknowledge the price, in deaths, disability, and environmental damage, of our global addiction to petrol.Cycle helmets do not improve safety but place responsibility for injury protection on the victim.As with smoking, the preferred public health policy would be to seek to remove the cause.
Myocardial Perforation by Ventriculoatrial-Shunt Tubing
Authors: Andrievs J. Dzenitis
Journal: JAMA (1965)

CERTAIN well-recognized complications not infrequently follow ventriculoatrial shunts, which are now regarded as the treatment of choice in infantile hydrocephalus.<sup>1-3</sup>Common causes necessitating removal or revision of the shunt are sepsis,<sup>4,5</sup>body growth, and mechanical separation or malfunction of the component parts.<sup>4,6,7</sup>The atrial tubing has been implicated in thromboemboli affecting the pulmonary circulation,<sup>5,6,8</sup>in cardiac arrhythmias,<sup>4</sup>in focal pericarditis, and in endocardial necrosis.<sup>6</sup> This is a report of a unique, well-documented complication of a ventriculoatrial shunt in which the distal silicone-rubber tubing perforated the wall of the right atrium, causing cerebrospinal fluid (CSF) accumulation in the pericardial sac. A similar case was cited by Anderson,<sup>1</sup>who successfully treated the patient with a single pericardial tap, but the etiology was never disclosed. Friedman and co-authors<sup>4</sup>refer to comparable experiences, but clinical information, treatment, eventual outcome, as well as possible mechanisms, are
An ethanol/ether soluble apoprotein from rat lung surfactant augments liposome uptake by isolated granular pneumocytes.
Authors: W D Claypool, D L Wang, A Chander, A B Fisher
Journal: Journal of Clinical Investigation (1984)

Ethanol/ether soluble apoproteins, comprising 17% of the total recovered surfactant-associated proteins, were isolated from rat lung surfactant and purified by silicic acid chromatography. The protein that eluted in 4:1 chloroform/methanol accounted for greater than 85% of protein in the ethanol/ether soluble fraction and was termed surfactant apoprotein Et (Apo Et). By sodium dodecyl sulfate polyacrylamide gel electrophoresis, this protein had an apparent molecular weight of approximately 10,500. Apo Et was evaluated for its effect on uptake of synthetic phospholipids in liposomal form by isolated granular pneumocytes (Type II alveolar epithelial cells) in primary culture. Liposomes were prepared to approximate the phospholipid composition of the alveolar surfactant, and uptake was measured by the accumulation of the radioactively labeled dipalmitoyl phosphatidyl choline fraction. The uptake of liposomal phosphatidylcholine by cells incubated for 2 h with Apo Et was increased by 61% over control. Most of the cell-associated phospholipid uptake was resistant to treatment with trypsin, suggesting an increased internalization of liposomal material in the presence of Apo Et. The effect of Apo Et on uptake was concentration and time dependent and was not associated with cell damage, phospholipase activity, or detergent properties of the protein. Apo Et had no significant effect on phosphatidylcholine uptake by granular pneumocytes maintained for 7 d in primary culture. Apo Et augmented the uptake of phospholipids by alveolar macrophages although total uptake by these cells was less than that observed with granular pneumocytes. Because Apo Et increases the rate of uptake of surfactant phospholipids by alveolar cells (granular pneumocytes and alveolar macrophages), this protein may represent a physiologically important regulator for clearance of lung surfactant phospholipids.
Direct activation of CD8+ cytotoxic T lymphocytes by dendritic cells.
Authors: K Inaba, J W Young, R M Steinman
Journal: The Journal of Experimental Medicine (1987)

Recent experiments (11-13) have shown that antigen-specific, CD8+, CD4- T lymphocytes can be induced to proliferate and become killer cells in the absence of a second population of "helper" CD8-, CD4+ cells. We have studied early events in the activation of CD4+ and CD8+ T cell subsets in the primary mixed leukocyte reaction. Dendritic cells are a major if not essential accessory cell for the activation of both subpopulations. Antigen-bearing macrophages fail to stimulate unprimed CD8+ cells, but act as targets for the sensitized cytolytic lymphocytes that are induced by dendritic cells. The initial proliferative response is comparable for CD4+ and CD8+ lymphocyte subsets. For both subpopulations, dendritic cells efficiently cluster the responding lymphocytes on the first day and induce the release of IL-2. The data indicate that CD4+ and CD8+ lymphocytes can be activated by a similar mechanism, and illustrate the special role of dendritic cells in the sensitization stage of cell-mediated immunity.
Concurrent Scarlet Fever and Measles in Children
Authors: E. A. Dent
Journal: BMJ (1902)

two colonies of B. coli on one of the slope agar tubes, no other organism was found.Pericardiunm.-There were evidences of a slight plastic pericarditis, a few flakes of fibrin being adherent to the heart muscle.This condition was not diagnosed during life, and it was entirely owing to the restric- tions placed on the necropsy by the parents that none of the fi aid could be properly collected and examined.It is, however, quite permissible to reason that in all probability the condition was pneumonic in origin.Heart.-The right cavity was in a state of slight dilatation, and other- wise the whole organ was perfectly healthy.The valves were absolutely sound, and there was no evidence whatever of any existent endocarditis; and it is, further, a significant fact that no infarcts of any kind were met with in any of the internal organs examined.Elbow-joint.-Nosign of inflammation, swelling, or other abnormality was visible.However, I aspirated the joint with a sterile needle, and withdrew a few drops of practically clear fluid containing a small number of floating flocculi.Coverslips made direct from the fluid presented a few capsulated Gram-staining hastate cocci, but cultures both in blood broth and on blood agar remained sterile.I have, however, no doubt in my mind that the organisms were no other than genuine pneumococci.Middle Ear.-During the child's stay in the hospital no discharge or ear trouble ever manifeited itself.At the necropsy.however I introduced in the middle ear on each side a sterile pipette, but entirely failed to withdrawn even one drop of fluid.
Reply form Authors re: Bertrand Tombal. Continuous Improvement Versus Innovation: The Case for Sipuleucel-T. Eur Urol 2012;61:648–9
Authors: Guru Sonpavde, Giuseppe Di Lorenzo, Celestia S. Higano, Philip W. Kantoff, Ravi A. Madan, Neal D. Shore
Journal: European Urology (2011)
Abstract A44: Proprotein convertase furin in rhabdomyosarcoma progression: A potential target for pediatric sarcomas therapy?
Authors: Patricia Jaaks, Valentina D'Alessandro, Beat W. Schäfer, Michele Bernasconi
Journal: Cancer Research (2014)

Abstract To improve therapies for embryonal pediatric tumors such as rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, we have selected, by in vivo phage display, for peptides that bind to RMS with high specificity. We have shown that coupling of doxorubicin to RMS-P3, our lead RMS-targeting peptide, increases its therapeutic impact in a xenograft mouse model for RMS. We have identified furin as potential target for RMS binding peptide RMS-P3. Furin is a member of the proprotein convertases (PC), a family of ten serine proteases, which convert inactive proproteins into their active form. We have found consistent expression of furin in a panel of RMS cell lines and in RMS biopsies at the mRNA level. To elucidate the contribution of furin to RMS growth we have generated a panel of RMS cell lines either overexpressing furin, or a specific intrinsic PC inhibitor called α1-PDX, as well as RMS cell lines were expression of furin has been stably reduced by shRNA. These cells have been tested for their growth, migration and invasion potential in vitro as well as for their growth in vivo as subcutaneous xenografts. The results suggest a direct correlation between furin activity and RMS cells migration and invasive properties in vitro as well as RMS tumor growth in vivo. Interestingly, alveolar RMS cells display a higher furin activity compared to embryonal RMS cells. Alveolar RMS cells growth in vivo cannot be further enhanced by furin overexpression, in contrast to embryonal RMS cells, suggesting a causal link between high furin activity and alveolar RMS malignant phenotype. Among the known furin substrates, which are processed and activated by furin, and involved in tumor growth, migration and invasion, we found a direct correlation between furin activity and IGFR1 activation. Our results suggest that furin plays a relevant role in RMS progression through enhanced activation of the IGF1R pathway, among others, and that it might represent a viable target for therapeutic intervention in RMS. This warrants further studies in the development of novel therapeutic approaches for RMS based both on specific inhibition of its activity and on targeted drug delivery by furin targeting peptides. Citation Format: Patricia Jaaks, Valentina D'Alessandro, Beat W. Schäfer, Michele Bernasconi.{Authors}. Proprotein convertase furin in rhabdomyosarcoma progression: A potential target for pediatric sarcomas therapy? [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A44.
Limits of anonymisation in NHS data systems
Authors: I. Brown, L. Brown, D. Korff
Journal: BMJ (2011)

Smyth discusses the recent report from the Academy of Medical Sciences on research regulation.1 2 The expert group’s reliance on anonymity to protect participants in research was based on assumptions about key NHS patient data systems that may no longer be justified in an era of ubiquitous data generation and sharing. The report also pays insufficient attention to patient autonomy. Patients are not currently being adequately informed about possible secondary uses of their medical …
Payment of financial incentives to GPs may invalidate informed consent process
Authors: C. Ferguson
Journal: BMJ (1998)

Editor—The fraud committed by Dr John Anderton1 was not academic fraud, as in other recent cases, but financial fraud inspired by the large payments now made by drug companies to doctors to enter patients in trials. Within hospital departments this income is usually put into research funds, but in general practice the doctor is often personally remunerated. This is now sufficiently lucrative that some general practitioners have reduced their clinical work and set …
Sodium and Potassium Sensitivity of Calcium Uptake and Calcium Binding by Dog Cardiac Microsomes
Authors: ARNOLD M. KATZ, DORIS I. REPKE
Journal: Circulation Research (1967)

Concentrations of KCl and NaCl below 1.0 M increased Ca uptake (in the presence of oxalate) by dog cardiac microsomes purified on sucrose density gradients; higher concentrations of these salts decreased Ca uptake. At lower microsome concentrations, where calcium uptake was maximal, replacement of KCl by equimolar amounts of NaCl decreased both the rate and extent of Ca uptake. The uptake of Ca in mixtures of NaCl and KCl was that expected from the presence of each cation alone, and bore no obvious relationship to the (Na + + K + )-activated ATPase associated with sodium transport. Ca binding (in the absence of oxalate) was increased by concentrations of NaCl and KCl up to approximately 0.12 M when the reaction mixture contained 5 mM ATP; higher concentrations of the alkali-metal salts reduced Ca binding. A similar dual action of Na + and K + on Ca binding was seen in the absence of ATP, but Ca binding was maximal at approximately 0.01 M KCl. The reduced Ca binding at high concentrations of KCl in the presence of ATP showed some characteristics suggesting competition between K + and Ca 2+ for a single binding site, but double reciprocal plots of the data did not meet the strict criteria for a classical competitive reaction. Thus, while these microsomal membranes show some of the properties of an ion exchanger, these interactions are more complex, in that, at low ionic strengths, Ca binding is facilitated by addition of alkali-metal salts. Ca binding was not altered by replacing K + with Na + , and specific competition between Na + and Ca 2+ was not seen in deoxycholate-treated or sonicated microsomes. Thus, the site for the proposed Na + -Ca 2+ competition that controls myocardial contractility has not been found.
HCV animal models and liver disease
Authors: Koen Vercauteren, Ype P. de Jong, Philip Meuleman
Journal: Journal of Hepatology (2014)

The development and evaluation of effective therapies and vaccines for the hepatitis C virus (HCV) and the study of its interactions with the mammalian host have been hindered for a long time by the absence of suitable small animal models. Due to the narrow host tropism of HCV, the development of mice that can be robustly engrafted with human hepatocytes was a major breakthrough since they recapitulate the complete HCV life cycle. This model has been useful to investigate many aspects of the HCV life cycle, including antiviral interventions. However, studies of cellular immunity, immunopathogenesis and resulting liver diseases have been hampered by the lack of a small animal model with a functional immune system. In this review, we summarize the evolution of in vivo models for the study of HCV.
Cardiac Troponin I Is Modified in the Myocardium of Bypass Patients
Authors: J. L. McDonough, R. Labugger, W. Pickett, M. Y. Tse, S. MacKenzie, S. C. Pang, D. Atar, G. Ropchan, J. E. Van Eyk
Journal: Circulation (2001)

Background —Selective proteolysis of cardiac troponin I (cTnI) is a proposed mechanism of contractile dysfunction in stunned myocardium, and the presence of cTnI degradation products in serum may reflect the functional state of the remaining viable myocardium. However, recent swine and canine studies have not demonstrated stunning-dependent cTnI degradation. Methods and Results —To address the universality of cTnI modification, myocardial biopsy samples were obtained from coronary artery bypass patients (n=37) before and 10 minutes after removal of cross-clamp. Analysis of biopsy samples for cTnI by Western blotting revealed a spectrum of modified cTnI products in myocardium both before and after cross-clamp, including degradation products (7 products resulting from differential N- and C-terminal processing) and covalent complexes (3 products). In particular, a 22-kDa cTnI degradation product with C-terminal proteolysis was identified, which may represent an initial ischemia-dependent cTnI modification, similar to cTnI 1–193 observed in stunned rat myocardium. Although no systematic change in amount of modified cTnI was observed, subgroups of patients displayed an increase (n=10, 85±5% of cTnI remaining intact before cross-clamp versus 75±5% after) or a decrease (n=12, 67±5% before versus 78±5% after). Electron microscopy demonstrated normal ultrastructure in biopsy samples, which suggests no necrosis was present. In addition, cTnI modification products were observed in serum through a modified SDS-PAGE methodology. Conclusions —cTnI modification, in particular proteolysis, occurs in myocardium of bypass patients and may play a key role in stunning in some bypass patients.
Feasibility and Acute Efficacy of Radiofrequency Ablation of Cavotricuspid Isthmus–Dependent Atrial Flutter Guided by Real-Time 3D TEE
Authors: François Regoli, Francesco F. Faletra, Gaetano Nucifora, Elena Pasotti, Tiziano Moccetti, Catherine Klersy, Angelo Auricchio
Journal: JACC. Cardiovascular imaging (2011)
Review of Timothy E. Quill and Margaret P. Battin (eds.),<i>Physician-Assisted Dying: The Case for Palliative Care &amp; Patient Care</i><sup>1</sup>and Kathleen Foley and Herbert Hendin (eds.),<i>The Case Against Assisted Suicide: For the Right to End-of-Life Care</i>.<sup>2</sup>
Authors: C. Wayne Mayhall
Journal: The American Journal of Bioethics (2007)

Is it metaphysical conceit for those of us who argue for or against physician-assisted suicide to assume, simply because we apply uncompromising scholarly standards to researching the case, we have...
Abstract 4238: BROMO<i>scan</i> - a high throughput, quantitative ligand binding platform identifies best-in-class bromodomain inhibitors from a screen of mature compounds targeting other protein classes.
Authors: Elizabeth Quinn, Lisa Wodicka, Pietro Ciceri, Gabriel Pallares, Elyssa Pickle, Adam Torrey, Mark Floyd, Jeremy Hunt, Daniel Treiber
Journal: Cancer Research (2013)

Abstract Post-translationally appended acetyllysine marks on histone tails are key regulatory features of the epigenetic code. Bromodomains are “readers” of this specific lysine acetylation code, playing an important role in chromatin remodeling and regulation of gene expression. Bromodomains have emerged as an important new druggable target class in small-molecule inhibitor drug discovery, and several bromodomain-containing proteins have been associated with disease. There are 57 bromodomains contained in 41 different proteins; however, few small molecule bromodomain inhibitors have been reported. One primary factor limiting the discovery of new inhibitors is the absence of a comprehensive biochemical bromodomain screening platform. Here we describe the application of DiscoveRx Corporation's proven ligand binding assay technology (KINOMEscan) to the development of quantitative ligand binding assays for human bromodomains (BROMOscan). We have developed a carefully validated assay panel that covers &amp;gt;30 percent of the human bromodomain family, and this panel is suitable for HTS, selectivity profiling, and quantitative affinity (Kd) assessment. We have used this panel internally to identify novel bromodomain inhibitors and, remarkably, have demonstrated that known, mature inhibitors thought to be selective for targets from other protein families have best in class affinity for bromodomains as well. These data shall be presented, as will a description of the BROMOscan panel replete with extensive assay validation data. Citation Format: Elizabeth Quinn, Lisa Wodicka, Pietro Ciceri, Gabriel Pallares, Elyssa Pickle, Adam Torrey, Mark Floyd, Jeremy Hunt, Daniel Treiber. BROMOscan - a high throughput, quantitative ligand binding platform identifies best-in-class bromodomain inhibitors from a screen of mature compounds targeting other protein classes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4238. doi:10.1158/1538-7445.AM2013-4238