tbuckley/cabot-search huggingface dataset:
Nitroglycerin for Angina Pectoris-Reply
Authors: Oglesby Paul
Journal: JAMA (1978)

I like the comments by Dr Herbert Copelan. My recommendation regarding a renewal of the supply of nitroglycerin every six months was an approximation of what is ideal; as he indicates, this might be too late if the drug is low in potency when purchased. As to the headache, again I agree that the response is variable, but it is useful. Sublingual burning is not always noted by patients.
Patterns of Ventricular Activity During Catheter Defibrillation
Authors: MORTON M. MOWER, M. MIROWSKI, JOSEPH F. SPEAR, E. NEIL MOORE
Journal: Circulation (1974)

In order to clarify the mechanism of ventricular catheter defibrillation in which the electrode distribution and the low energy requirements make a simultaneous depolarization of the entire myocardium unlikely, the electrocardiograms recorded during 120 catheter fibrillation-defibrillation episodes in 39 dogs were analyzed. Three distinct, equally distributed defibrillation patterns were observed: 1) immediate resumption of a coordinated rhythm, thought to reflect complete depolarization of the myocardium; 2) increasing coarsening of the fibrillation waveforms interpreted as progressive reduction in the number of fibrillating fibers with reversion when a critical mass of myocardium with synchronized activity is reached, and 3) production of more coordinated "flutter-like" ventricular complexes probably representing a rhythm distinct from fibrillation and convertible to sinus rhythm by a second subthreshold shock. These observations suggest that total depolarization of the entire myocardium is not a prerequisite for ventricular defibrillation.
Whole-genome sequencing to control antimicrobial resistance
Authors: Claudio U. Köser, Matthew J. Ellington, Sharon J. Peacock
Journal: Trends in Genetics (2014)

Following recent improvements in sequencing technologies, whole-genome sequencing (WGS) is positioned to become an essential tool in the control of antibiotic resistance, a major threat in modern healthcare. WGS has already found numerous applications in this area, ranging from the development of novel antibiotics and diagnostic tests through to antibiotic stewardship of currently available drugs via surveillance and the elucidation of the factors that allow the emergence and persistence of resistance. Numerous proof-of-principle studies have also highlighted the value of WGS as a tool for day-to-day infection control and, for some pathogens, as a primary diagnostic tool to detect antibiotic resistance. However, appropriate data analysis platforms will need to be developed before routine WGS can be introduced on a large scale.
Perioral pustular eruption caused by Candida albicans
Authors: FLEMMING BRANDRUP, GUNHILD LANGE WANTZIN, KRISTIAN THOMSEN
Journal: British Journal of Dermatology (1981)

A 22‐year‐old female and a 60‐year‐old male suddenly developed perioral erythematous infiltration with multiple papular and pustular lesions similar to acne conglobata. Many colonies of Candida albicans were cultured from pustules prior to systemic treatment with antibiotics and topical anticandidal treatment. After healing of the lesions with some scarring, Candida albicans could not be cultured.
Technology Assessment for New Oncology Drugs
Authors: Bengt Jönsson
Journal: Clinical Cancer Research (2013)

Abstract Health technology assessment (HTA) has become the key health policy instrument for managing the introduction and use of new oncology drugs in Europe. While the methodology of technology assessment, including calculations of cost-effectiveness, is applicable in principle also to oncology, the implementation in practice has its specific problems and consequences. Most of them are linked to the specific need to do the assessment early in the development, with limited data on outcome in clinical practice. Technology assessments ask for estimates of gains in mean survival, whereas trials are powered to study differences in progression-free or overall median survival. The development of targeted therapies and personalized cancer medicine offers opportunities but also increases the complexity of the assessment. Joint assessment of a diagnostic and a new treatment increases the number intervention strategies that must be considered, and thus the need for data. The translation from efficacy in trials to relative effectiveness in clinical practice must also be considered. The close link between pricing of new oncology drugs and their cost-effectiveness makes the use of technology assessment for policy decisions complicated for all stakeholders involved. But without an obvious alternative that is better, the likely future is that HTA will play an increasing role in informing policy decisions aimed at evidence-based cancer care. Clin Cancer Res; 19(1); 6–11. ©2013 AACR.
Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer’s disease
Authors: Elena Marcello, Claudia Saraceno, Stefano Musardo, Hugo Vara, Alerie Guzman de la Fuente, Silvia Pelucchi, Daniele Di Marino, Barbara Borroni, Anna Tramontano, Isabel Pérez-Otaño, Alessandro Padovani, Maurizio Giustetto, Fabrizio Gardoni, Monica Di Luca
Journal: Journal of Clinical Investigation (2013)

A disintegrin and metalloproteinase 10 (ADAM10), a disintegrin and metalloproteinase that resides in the postsynaptic densities (PSDs) of excitatory synapses, has previously been shown to limit β-amyloid peptide (Aβ) formation in Alzheimer's disease (AD). ADAM10 also plays a critical role in regulating functional membrane proteins at the synapse. Using human hippocampal homogenates, we found that ADAM10 removal from the plasma membrane was mediated by clathrin-dependent endocytosis. Additionally, we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. This domain was required for ADAM10 endocytosis and modulation of its plasma membrane levels. We found that the ADAM10/AP2 association was increased in the hippocampi of AD patients compared with healthy controls. Long-term potentiation (LTP) in hippocampal neuronal cultures induced ADAM10 endocytosis through AP2 association and decreased surface ADAM10 levels and activity. Conversely, long-term depression (LTD) promoted ADAM10 synaptic membrane insertion and stimulated its activity. ADAM10 interaction with the synapse-associated protein-97 (SAP97) was necessary for LTD-induced ADAM10 trafficking and required for LTD maintenance and LTD-induced changes in spine morphogenesis. These data identify and characterize a mechanism controlling ADAM10 localization and activity at excitatory synapses that is relevant to AD pathogenesis.
The Values of Psychotherapy
Authors: Steven S. Sharfstein
Journal: JAMA (1990)

"One may reasonably expect that at some time or other the conscience of the community will awake and admonish it that the poor man has just as much right to help for his mind as he now has for the surgeon's means for saving his life." (Freud<i>S. Lines of Ad-</i><i>vance in Psychoanalytic Therapy</i>. London, England: Hogarth; 1919;17:1953-1973, quoted page 85 in the "Values of Psychotherapy.") This book is an articulate, even passionate, defense of psychotherapy as a treatment that should be available to all in need. In it psychotherapy is defined in the broadest of terms as "the systematic use of a relationship between therapist and patient—as opposed to pharmacologic or social methods—to produce changes in cognition, feelings, and behavior." It is described as a treatment that not only brings symptomatic relief, but also allows the individual a much greater sense of experience, enhanced autonomy, and self-esteem. This
Binding of Pseudomonas cepacia to normal human intestinal mucin and respiratory mucin from patients with cystic fibrosis.
Authors: U S Sajjan, M Corey, M A Karmali, J F Forstner
Journal: Journal of Clinical Investigation (1992)

Although not as prevalent as Pseudomonas aeruginosa, Pseudomonas cepacia is another opportunistic pathogen which colonizes the lungs of at least some patients with cystic fibrosis. A subgroup of these patients exhibits the "cepacia syndrome", i.e., a rapid clinical deterioration and death within one year. To investigate potential early sites of bacterial attachment, we have measured the specific binding of P. cepacia isolates from cystic fibrosis (CF) sputa to both CF and non-CF mucins purified from respiratory and intestinal secretions, respectively. As shown in microtiter binding assays, clinical isolates from 19/22 patients were found to bind to both mucins, with the highest specific binding exhibited by isolates from eight patients, seven of whom later died with the cepacia syndrome. No differences were observed in the binding capacity of the two (CF versus non-CF) mucins. Binding was specific, saturable, and not influenced by tetramethylurea, a disruptor of hydrophobic associations. Individual sugars were ineffective as hapten inhibitors, as were several lectins. Mucins treated by reduction/alkylation or chloroform/methanol extraction showed enhanced bacterial binding, findings which were attributed to exposure of underlying binding sites. Deglycosylation procedures indicated that mucin receptors for P. cepacia include N-acetylglucosamine and N-acetylgalactosamine, probably linked together as part of core oligosaccharide structures. P. cepacia isolates also bound to buccal epithelial cells, and mucin partially inhibited the binding of those isolates of P. cepacia that also had the ability to bind to mucin. We speculate that specific binding of P. cepacia to secreted mucins may be an early step in the pathogenesis of the cepacia syndrome.
A good death?
Authors: A. Berger
Journal: BMJ (2003)

My father's death was all set to be the best a hospital could offer. He'd been virtually bed-bound in hospital for the past 10 months, and everyone who worked on his ward knew him and knew what was happening. Everyone agreed that he should not be resuscitated in the event of cardiorespiratory arrest, and eventually we asked that he should no longer be …
Delayed Diagnosis of Disease
Authors: Howard M. Spiro
Journal: JAMA (1985)

MANY methods to limit the costs of medical care are being scrutinized. Corporations are asking their employees to pay a larger portion of their "health care" bills; diagnosis-related groups have been introduced to limit the number of diagnostic studies and other related costs for each hospital illness. These and other external measures aim at financially restricting, "capping" is the word, what the physician can do. Why do physicians order so many tests; why do their patients so enthusiastically agree to them—when they do not demand them? Is it greed on the physician's part or fear or ignorance on the patient's? I do not think so. The new diagnostic and therapeutic techniques available in ever-increasing varieties to physicians since about 1970 make superb contributions to medical care and make the work of the clinician easier and much more precise. The problem lies not with the answers that the new technology provides,
Transendoscopic Doppler Ultrasound: Usefulness for Diagnosis and Treatment of Vascular Malformations
Authors: P. Rutgeerts, G. Vantrappen, F. D'Heygere, L. Broeckaert
Journal: Endoscopy (1988)

Vascular malformations of the GI tract can be treated by thermal methods, including the YAG laser. The diagnosis of these lesions is not always easy, and it is difficult to evaluate the completeness of therapy of these lesions. We investigated the value of Doppler ultrasound in this respect. The TVD-1 (Key Med) transendoscopic vascular detector using the 2.5 mm diameter probe emitting at 7 MHz, was used through standard endoscopes. Outputs were monitored through a loudspeaker, and imaged on an oscilloscope, or recorded on a mingograph. Diagnostic usefulness was studied in 64 vascular lesions, 36 in the colon and 28 in the upper GI tract in ten patients. A Doppler signal was detected in 75% of the lesions, including all lesions larger than 5 mm in diameter. Forty-five lesions in 13 patients were studied before and immediately after laser therapy. Three out of five patients in whom Doppler-positive lesions persisted after laser treatment rebled, as compared with 2 out of 8 patients with Doppler-negativity. Disappearance of the signal, however, may be transient, and is probably due to laser-induced edema. These results suggest that endoscopic Doppler ultrasound may have a role in the diagnosis and treatment of vascular anomalies of the GI tract, and should stimulate further research.
Scientists call for a boycott of Cell Press
Authors: J. Lenzer
Journal: BMJ (2003)

Two research scientists at the University of California at San Francisco have called for a boycott of Cell Press publications, saying the price for electronic access is exorbitant. Peter Walter and Keith Yamamoto, both professors at the University of California in San Francisco, have asked fellow scientists to stop submitting papers to Cell Press and to resign from the editorial boards of Cell Press, among other actions.

Cell Press, owned by Elsevier, publishes nine journals, including Cell and Neuron. Lynne Herndon, president and chief executive officer of Cell Press, said their pricing is reasonable as they estimate their charges at $1.50 (90p; €1.30) per journal per subscriber per year.

But the additional $90 …
Type 1 Diabetes — Does Suppressing T Cells Increase Insulin?
Authors: Åke Lernmark
Journal: New England Journal of Medicine (2005)

During the ominous prelude to the onset of type 1 diabetes, the pancreatic-islet beta cells become the targets of a specific autoimmune attack, which ultimately results in diabetes. Although major advances have led to an improved understanding of this disease, important gaps in knowledge must be bridged before insulin replacement is shelved forever. The report by Keymeulen et al.1 in this issue of the Journal is further testimony to how complicated it will be to find a treatment that is superior to insulin alone.The development of type 1 diabetes may be viewed as a two-step process. In the first . . .
LONGITUDINAL STRAIN INDEXED TO END-DIASTOLIC VOLUME CAN BETTER DISCRIMINATE ATHLETE'S HEART
Authors: Attila Kovács, Alexandra Assabiny, Bálint Lakatos, Astrid Apor, Andrea Nagy, Hajnalka Vágó, Attila Tóth, Bela Merkely
Journal: Journal of the American College of Cardiology (2014)
Abstract 2231: Development of bifunctional cross-linking agents to identify intermediate proteasomes.
Authors: Kimberly C. Carmony, Lalit Kumar Sharma, Kyung-Bo Kim
Journal: Cancer Research (2013)

Abstract Introduction: This research was conducted to develop bifunctional cross-linking agents that can be used to identify intermediate proteasomes. Two well-characterized proteasome subtypes, the constitutive proteasome and immunoproteasome, differ with respect to their distinct sets of catalytic subunits. Additionally, intermediate proteasome subtypes comprised of non-standard mixtures of catalytic subunits have more recently been discovered. These intermediate proteasomes differ from constitutive and immunoproteasomes in their proteolytic activity profiles, suggesting that they have unique cellular functions. In agreement with this, intermediate proteasomes in cancer cell lines were shown to play important roles in the production of several tumor antigens. However, largely due to limitations of methods currently available to distinguish between subtypes, the detailed functions of intermediate proteasomes remain poorly defined. Bifunctional agents capable of cross-linking two different catalytic subunits within a single proteasome complex will facilitate a simple approach to identify distinct proteasome subtypes present within cells. These compounds will serve as important chemical probes for investigating the functions of individual proteasome subtypes in cancer cells. Experimental Procedures: Bifunctional cross-linking agents were synthesized by coupling two broad-spectrum or subunit-selective proteasome inhibitors through hydrocarbon or polyethylene glycol linkers. Positions for derivatization of these inhibitors were selected based on computational modeling, and linker lengths were varied to increase cross-linking efficiency. The ability of the resulting compounds to cross-link two proteasome catalytic subunits in cancer cell lysates was assessed via western blotting. Competition assays with subunit-selective proteasome inhibitors were conducted to verify the identities of the cross-linked subunit pairs. Data Summary: The structures of the bifunctional cross-linking agents were confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy. Western blotting results revealed the ability of several of these bifunctional agents to cross-link two catalytic subunits within individual proteasome complexes, facilitating compositional analysis of distinct proteasome subtypes. Conclusions: We have successfully developed bifunctional agents capable of cross-linking two catalytic subunits within individual proteasome complexes. These compounds will be utilized in functional studies of intermediate proteasomes present within cancer cells. Citation Format: Kimberly C. Carmony, Lalit Kumar Sharma, Kyung-Bo Kim. Development of bifunctional cross-linking agents to identify intermediate proteasomes. [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 2231. doi:10.1158/1538-7445.AM2013-2231
Langerhans cell histiocytosis-clinicopathological reappraisal and human leucocyte antigen association
Authors: R.C. YU, A.C. CHU
Journal: British Journal of Dermatology (1996)

We have examined the clinicopathological correlates of 74 patients with histologically confirmed Langerhans cell histiocytosis. Factors that influenced disease outcome included, three or more organ/systems being involved, a disease onset before the age of 2 years, the involvement of certain vital organs/systems such as liver/spleen, bone marrow and lungs, and male gender. The total number of involved organs/systems was the single most important determinant of disease outcome. Mortality rate in patients with three or more organs/systems involved, was 26%, as compared with 0% in the group with one or two organs/systems involved (chi 2 = 11.2, P = 0.008). There were no familial cases in our series, but we looked for a possible immunogenetic association by tissue typing 46 Caucasian sufferers and comparing the results with 117 controls. We used normal peripheral blood lymphocytes in 39 cases, Epstein-Barr virus-transformed lymphoblastoid cell lines in 12 cases, and both peripheral blood and Epstein-Barr virus-transformed lymphocytes in five cases. The HLA-B7 antigen was significantly increased Langerhans cell histiocytosis patients (19 of 46 = 41.3%) compared with 19 of 117 (16.2%) in the control group chi 2 = 11.2, relative risk = 3.6, P value after correction = 0.013). Attempt to stratify the disease into single-system or multisystem disease did not result in any significant association.
GPs should not have routine role in authorising handguns Juniors issue guidance on "English clause" Minister says there are recruitment problems in general practice British doctors returning from abroad and specialist training Bradford GPs win out of hours award Senior hospital doctors complain about manpower "black hole" GPs' staff should have NHS pensions
Authors: L. Beecham
Journal: BMJ (1996)

In its evidence to the Cullen inquiry into the possession of handguns following the Dunblane massacre, the General Medical Services Committee says that the position of doctors as potential countersignatories of applications for shotgun and firearm certificates is unsatisfactory. The committee says that general practitioners should have no routine role in the process by which certificates are issued because of the lack of scientific evidence that such involvement would predict future violence. Doctors should be told when their patient has been issued with a certificate. Under the General Medical Council's guidance doctors are able to disclose information without consent if this would avert the risk of death or serious harm. The GMSC recommends that a confidential helpline should be set up at the Home Office, the Scottish Office, and the Welsh Office to allow doctors to disclose information about a perceived risk of violence through the use of firearms to a fellow professional.

# Juniors issue guidance on “English clause” {#article-title-2}

The Junior Doctors Committee has issued revised guidance on when the “English clause” can be invoked. The terms of service provide that after 31 December 1996 higher specialist trainees may continue to contract for duties in excess of a 72 hour maximum average per week (though not more than an average of 83 hours) “providing proper support staffing exists and providing the duties are not harmful either to the trainees or to patients.” The doctors must be willing to do the extra hours, which should benefit their training. It will be …
Abstract 1448: Novel ALK5 inhibitor as an anti-metastasis agent in both breast cancer cells <i>in vitro</i> and MMTV/cNeu transgenic mice <i>in vivo</i>
Authors: Chul-Yong Park, Bo M. Kang, In H. Kwon, So J. Moon, Jee Y. Son, Eun J. Yoon, Dae-Kee Kim, Yhun Y. Sheen
Journal: Cancer Research (2010)

Abstract We have synthesized novel ALK5 inhibitors and investigated their effects of on breast cancer cells as well as tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice. The treatment of ALK5 inhibitors into breast tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice inhibited lung metastasis compared to that of untreated animal. The level of ß-casein in the lung of the breast tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice were decreased by ALK5 inhibitor treatment. The levels of CXCR4, MMP2 and MMP9 were decreased in the lung and breast tumor of ALK5 inhibitors treated breast tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice. The action mechanisms of new ALK5 inhibitors were investigated in both breast cancer cells and breast cancer mice model. TGFß signaling, phosphorylated smad2/3 based from the western blot analysis in vitro and in vivo as well as confocal microscopic analysis in vitro was decreased by ALK5 inhibitors. And also, results from wound healing assay and invasion assay showed strong inhibition of TGFß action by new ALK5 inhibitors. This data strongly argue that ALK5 inhibitors have anti-metastasis effects via inhibiting ALK5 activity in vivo and in vitro. In order to gain further insight into the mechanism of ALK5 inhibitor, we have carried out experiment to examine the effects of ALK5 inhibitor in human breast cancer MDA-MB-231 cell. TGFß stimulated mesenchymal markers of epithelial mesenchymal transition (EMT), such as Snail, TWIST, N-cadherin and these were inhibited by ALK5 inhibitor concomitant treatment. Also, TGFß increased tumor invasion markers such as MMP2, and MMP9 which were inhibited by ALK5 inhibitor concomitant treatment. In addition, ALK5 inhibitors recover the level of E-cadherin, SnoN, Ski which were downregulated by TGFß treatment. In summary, ALK5 inhibitors have anti-metastatic effect on human breast cancer cells as well as tumor bearing MMTV/cNeu transgenic mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1448.