tbuckley/cabot-search huggingface dataset:
Ribavirin for Chronic Hepatitis E Virus Infection in Transplant Recipients
Authors: Nassim Kamar, Jacques Izopet, Simona Tripon, Michael Bismuth, Sophie Hillaire, Jérôme Dumortier, Sylvie Radenne, Audrey Coilly, Valérie Garrigue, Louis D'Alteroche, Matthias Buchler, Lionel Couzi, Pascal Lebray, Sebastien Dharancy, Anne Minello, Maryvonne Hourmant, Anne-Marie Roque-Afonso, Florence Abravanel, Stanislas Pol, Lionel Rostaing, Vincent Mallet
Journal: New England Journal of Medicine (2014)

There is no established therapy for hepatitis E virus (HEV) infection. The aim of this retrospective, multicenter case series was to assess the effects of ribavirin as monotherapy for solid-organ transplant recipients with prolonged HEV viremia.
Studies on the Production of Intravascular Thrombi and Their Treatment with Fibrinolysin
Authors: A. H. FREIMAN, N. U. BANG, E. E. CLIFFTON
Journal: Circulation Research (1960)

In 22 dogs, the effect of fibrinolysin therapy of fresh intravascular clots was evaluated by serial angiograms and autopsies. The average time required for dissolution of such clots, when treated by systemic plasmin, was 4 hours and 45 minutes, while the average time necessary for lysis with local fibrinolytic therapy was 2 hours 10 minutes. Treatment of fresh venous and arterial clots did not disclose any significant difference in susceptibility to lysis. In 21 dogs, the effect of age of the clot on the effectiveness of plasmin therapy was studied in clots formed with serum and morrhuate. Clots treated within 4 days of formation were susceptible to dissolution, although clots treated after 3 days did not uniformly undergo complete lysis. The serum-induced clots were more amenable to fibrinolytic therapy than were those formed with morrhuate.
Surgeon Volume vs Hospital Volume: Which Matters More?
Authors: Hugh G. Beebe
Journal: JAMA (1990)

<h3>To the Editor.—</h3> In the editorial<sup>1</sup>discussing the provocative study of the relationship between volume and mortality by Hannan et al,<sup>2</sup>Garnick and colleagues<sup>1</sup>pose many important questions yet to be considered. They do conclude, however, that "directing patients toward higher-volume surgeons and hospitals for certain procedures has the potential to improve overall patient outcomes." It should also be considered whether so directing patients has the potential for worsening patient outcomes or for worsening the relationship between physician and patient. Being a practicing surgeon who has worked in two very different settings, a large, high-volume clinic and a full-time academic position, I see the potential for harm in somehow directing patients to surgeons who are already "high-volume" practitioners. There is a point beyond which time becomes the enemy and shortcuts to conserve time erode the quality of both technical surgery and the relationship with the patient. The
"Don't forget the meatballs, Mum"
Authors: J. Hollis-Trantafillou
Journal: BMJ (1996)

You've made it sound too easy,” complained Sheila as she perched on the corner of my desk reading the draft of my previous article on foreign wives [BMJ 13 April]. Being one herself with seemingly insoluble domestic problems she had a perfect right to criticise. “It's all very well getting lyrical over victories being fought for but what about the sheer teethgrinding everyday struggle to communicate in a language with five ‘e's and having to remember the gender of a chair and always missing out on the best jokes? And what about the marriages wrecked by interfering mothers in law; and what about the culturally …
Research in the Hot Zone
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2006)

Research conducted at biosafety level 4, popularly known as the hot zone, continues to be both revered and feared. Biosafety level 4 laboratories are the places to study dangerous and exotic agents that cannot safely be studied anywhere else, such as pathogens that can be transmitted within a laboratory through the air. This level of biosafety is often required for the development of diagnostic tests, therapies, and vaccines and as the starting point for work on newly recognized agents whose risks have yet to be established.1 At the same time, these laboratories are seen as potential targets of a terrorist . . .
Interstitial Fibrosis After Pneumocystis carinii Pneumonia
Authors: MICHAEL E. WHITCOMB
Journal: Annals of Internal Medicine (1970)

Serial pulmonary function studies were performed during the convalescent stage on a patient who survived biopsy-proved Pneumocystis carinii pneumonia. A lung biopsy specimen was obtained 5 months after the onset of the acute illness. These studies documented the presence of diffuse interstitial fibrosis of the lung and strongly suggested that the fibrosis developed as a sequel to Pneumocystis carinii infection. This observation is consistent with the theory that diffuse interstitial pneumonitis of infectious cause may progress to diffuse interstitial fibrosis.
Rape and sexual assault
Authors: Jan Welch, Fiona Mason
Journal: BMJ (2007)

Sexual violence is a global problem.The lifetime risk of attempted or completed rape is up to 20% for women, but men and children are also often sexually violated. 1Sequelae include unwanted pregnancies; sexually transmitted infections, including HIV; depression; and posttraumatic stress disorder.Most of the literature on rape and sexual assault is retrospective, but we aim to provide an evidence based review of their management.
TCT-843 Transcatheter Aortic Valve Implantation with Edwards SAPIEN XT™ versus Medtronic CoreValve Revalving System® with AccuTrak™: The SAPERE Pilot Study
Authors: Gill Buchanan, Alaide Chieffo, Matteo Montorfano, Francesco Maisano, Azeem Latib, Micaela Cioni, Mauro Carlino, Filippo Figini, Irene Franzoni, Alessandro Durante, Annalisa Franco, Remo Covello, Chiara Gerli, Eustachio Agricola, Giovanni La Canna, Pietro Spagnolo, Ottavio Alfieri, Antonio Colombo
Journal: Journal of the American College of Cardiology (2012)
A Survey of Employment Policies as Related to Cardiac Patients in Greater Boston
Authors: Simon Olshansky, Seymour Friedland, Richard J. Clark, Howard B. Sprague
Journal: New England Journal of Medicine (1955)

DURING the summer of 1954 the Massachusetts Heart Association, being concerned with the situation of the cardiac patient in industry, sponsored a survey for the purpose of discovering facts involved in the hiring, rejection and retention of this working group. It was desired to learn the policies of various employers and what the factors determining them might be.The Study and Its ScopeA study was made of 100 employers in the Greater Boston Area, including 51 in manufacturing and 49 in nonmanufacturing groups. Employers ranged from those employing under 100 to those with more than 20,000 workers, the largest . . .
Antiidiotypic Antibodies as Probes for Receptor Structure and Function
Authors: Nadir R. Farid, Theodore C.Y. Lo
Journal: Endocrine Reviews (1985)

The immune system has evolved to recognize itself and respond to nonself (antigens) within the context of self (1, 2). The immune response needs to be specific, augmentable and yet limited in extent and temporally to the defense requirements of the organism (1, 2). Rearrangement of immunoglobulin (Ig)1 genes brings one VH segment into proximity with those of one of several J segments and a single CL segment and VH, D, J, and one of eight CH segments to assemble active light and heavy chain genes, respectively. This process entails somatic recombination and RNA splicing. The large number of gene line components to choose from, point mutations in V region and flexibility of the recombinational process between certain segments contribute to the extraordinary antibody diversity (2, 3).
Mortality in patients with testicular cancer: report of the Anglia and Trent testicular tumour groups.
Authors: M Ellis, K Sikora
Journal: BMJ (1986)

The overall prognosis of patients with testicular cancer has improved dramatically over the past decade. Most patients are now treated in regional oncology centres in general hospitals. The cause of death was determined in 52 patients in the East Anglian and Trent regions who presented between 1980 and 1984. The overall mortality was 10.8%. Thirty four patients died with progressive disease, 12 of treatment related problems, two suddenly at home in between chemotherapy courses, and four of incidental causes. Reasons for treatment failure and for the deaths related to treatment were analysed and several recommendations made to reduce the death rate in this highly curable disease predominantly of young men.
Central Melanocortin Signaling Restores Skeletal Muscle AMP-Activated Protein Kinase Phosphorylation in Mice Fed a High-Fat Diet
Authors: Tomohiro Tanaka, Hiroaki Masuzaki, Shintaro Yasue, Ken Ebihara, Tetsuya Shiuchi, Takako Ishii, Naoki Arai, Masakazu Hirata, Hiroshi Yamamoto, Tatsuya Hayashi, Kiminori Hosoda, Yasuhiko Minokoshi, Kazuwa Nakao
Journal: Cell Metabolism (2007)
Late presentation, late diagnosis, late stage diagnosis, delayed diagnosis, delayed presentation: terminology confuses the message in UK cancer policy
Authors: M. S. Day
Journal: BMJ (2012)

Cancer survival rates make big headlines. Recently the government has used survival rates as part of the case for the major NHS structural reforms, and it is estimated that up to 10 000 lives a year could be saved in England if we had the best survival rates in Europe.1

So, to catch up with our European neighbours, patients need to be diagnosed earlier. Or do they need to present earlier? Which ever it is, the overall message is clear: the earlier your diagnosis, the better your chances. But less clear is the collection of phrases used when talking about cancer survival, from the media to government policy documents.

To untangle these phrases we need to delve a little deeper. What constitutes an early or late diagnosis of cancer? In the UK, the term “late diagnosis” usually means a late stage tumour, one that is locally advanced or has metastasised. Studies reporting cancer survival will use the TNM (tumour size; spread to lymph nodes; metastasis) staging system to identify these “late stage” tumours. …
While Rome burns
Authors: Fiona Godlee
Journal: BMJ (2006)

Something strange is happening in the NHS. I don't mean the chaos of constant policy change, the threat of closures, the job losses, the financial crises—we are used to all that. No, I mean that although the service functions and patients are seen and treated, many of them satisfactorily, something important is quietly dying. I don't think it is too fanciful to call it the spirit of medical professionalism. And we, the medical profession, are watching it die.

We asked Nigel Hawkes, an experienced health journalist, to give us his take on the NHS reforms (p 645). The result was …
Albuminuric Retinitis of Pregnancy
Authors: A. Emrys-Jones
Journal: BMJ (1883)

tion.I would go so far as to say that, if the patient be suffering from recurring attacks of this so-called inflammation, it will be not only justifiable, but the best practice, to make an exploratory inci- sion, and remove the cause of the trouble, or whatever may be found necessary.Doubtless, many of the cases which are classed as chronic ovaritis are, in reality, at first attacks of pelvic peritonitis, which results in adherent ovary, adherent tube, and the consequent loss of the normal relation between the tube and ovary.Hence the acquired sterility so frequently observed.
Simultaneous Visualization of a Mandibular Brown Tumor With a Large Parathyroid Adenoma on Tc-99m MIBI Imaging
Authors: A Fuat Yapar, Mehmet Aydin, Mehmet Reyhan, Nebil Bal, Zeynep Yapar, Nazli Altun Yologlu
Journal: Clinical Nuclear Medicine (2005)

Double-phase scintigraphy using Tc-99m MIBI is the study of choice for detecting parathyroid adenomas in patients with primary hyperparathyroidism. Brown tumors are characteristic tumors of hyperparathyroidism, which have been reported to take up Tl-201 and Tc-99m MIBI when parathyroid scintigraphy was performed. We report a case in which a large parathyroid adenoma and a brown tumor localized in the mandible and were visualized simultaneously in double-phase Tc-99m MIBI parathyroid imaging.
Immunocompromised patient with an ulcerated nasolabial skin lesion
Authors: E. P. Prokopakis, I. E. Panagiotaki, I. A. Papadakis, A. S. Vardouniotis, G. M. Lagoudianakis, G. A. Velegrakis
Journal: BMJ (2010)

An 83 year old man was referred to us from the department of haematology because he had an exophytic and ulcerated nasolabial skin lesion. The lesion had been present for 6 months and caused severe facial pain, itching, foul odour, and dry eyes. The patient’s history included myelodysplastic syndrome, hypothyroidism, mild hypertension, mitral and aortic valve regurgitation, and paroxysmal atrial fibrillation. Physical examination revealed an extensive reddish and crusted nasolabial facial lesion that extended to the nasal cruses, causing left eyelid swelling and severe ectropion.⇓ The lesion was accompanied by some smaller lesions on the right mandible and cheek. The patient also had severe stenosis of the left nasal valve, which made nasal endoscopy particularly difficult. No enlarged cervical lymph nodes or other pathological physical findings were noted. Laboratory tests showed mild leucopenia (white blood cell count 3300 per μl), neutropenia (polymorphonuclear leukocyte count 900 per μl), and thrombopenia (platelet count 89 000 per μl), with normocytic and normochromic anaemia (haematocrit 27.3%, haemoglobin 8.3 g/dl, red blood cell count 2.8×103 per μl). Computed tomography revealed skin thickening of the anterior nose and maxilla, as well as opacity of the subcutaneous fat and increased iodine contrast intake, with no evidence of bone infiltration. The maxillary and ethmoid sinuses were congested by thick mucous secretions. The patient had received high doses of antibiotics in the department of haematology to treat his myelodysplastic syndrome; therefore, the facial lesion could have a possible infectious origin. The smear cultures from the lesion and the patient’s blood were negative for bacteria, parasites, and fungi.
Effects of Maternal Separation
Authors: Tracy Hampton
Journal: JAMA (2012)

Separation from mothers at birth has long-lasting harmful effects on health that are not remedied by a normal social environment later in life, according to a recent study in primates (Conti G et al. Proc Natl Acad Sci U S A. doi: 10.1073/pnas.1205340109 [published online May 21, 2012]).
Selective Rep-Cap Gene Amplification as a Mechanism for High-Titer Recombinant AAV Production from Stable Cell Lines
Authors: Xingluo Liu, Frosso Voulgaropoulou, Ruju Chen, Philip R. Johnson, K. Reed Clark
Journal: Molecular Therapy (2000)

Gene transfer vectors based on adeno-associated virus mediate high-level, stable gene expression in a variety of postmitotic tissues; thus, there is interest in developing improved production systems. We previously described the generation of rAAV producer cell lines that, upon infection with adenovirus, yielded biologically active rAAV particles. In these studies we show that the adenovirus multiplicity of infection (m.o.i.) is a critical variable for efficient production of cell line-derived rAAV and can affect yields by over 200-fold. Moreover, a threshold level of adenovirus was found necessary for high-titer vector production. To define the possible factors responsible for adenovirus m.o.i. -dependent rAAV yields, we analyzed rep and cap expression as a function of adenovirus m.o.i. High-level AAV capsid protein synthesis was observed in rAAV producer cells at adenovirus m.o.i. > or =10. This prompted us to analyze the rep-cap copy number following adenovirus infection. We documented robust episomal DNA amplification (100-fold) of integrated rep-cap sequences. Interestingly, no amplification of rep-cap sequences was observed when the sequences (in plasmid form) were transfected into adenovirus-infected HeLa cells. These data suggest that adenovirus-dependent rep-cap gene amplification is a critical process responsible for efficient rAAV synthesis in stable cell lines.
A Multidimensional Index and Staging System for Idiopathic Pulmonary Fibrosis
Authors: Brett Ley, Christopher J. Ryerson, Eric Vittinghoff, Jay H. Ryu, Sara Tomassetti, Joyce S. Lee, Venerino Poletti, Matteo Buccioli, Brett M. Elicker, Kirk D. Jones, Talmadge E. King, Harold R. Collard
Journal: Annals of Internal Medicine (2012)

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an overall poor prognosis. A simple-to-use staging system for IPF may improve prognostication, help guide management, and facilitate research. Objective: To develop a multidimensional prognostic staging system for IPF by using commonly measured clinical and physiologic variables. Design: A clinical prediction model was developed and validated by using retrospective data from 3 large, geographically distinct cohorts. Setting: Interstitial lung disease referral centers in California, Minnesota, and Italy. Patients: 228 patients with IPF at the University of California, San Francisco (derivation cohort), and 330 patients at the Mayo Clinic and Morgagni-Pierantoni Hospital (validation cohort). Measurements: The primary outcome was mortality, treating transplantation as a competing risk. Model discrimination was assessed by the c-index, and calibration was assessed by comparing predicted and observed cumulative mortality at 1, 2, and 3 years. Results: Four variables were included in the final model: gender (G), age (A), and 2 lung physiology variables (P) (FVC and Dlco). A model using continuous predictors (GAP calculator) and a simple point-scoring system (GAP index) performed similarly in derivation (c-index of 70.8 and 69.3, respectively) and validation (c-index of 69.1 and 68.7, respectively). Three stages (stages I, II, and III) were identified based on the GAP index with 1-year mortality of 6%, 16%, and 39%, respectively. The GAP models performed similarly in pooled follow-up visits (c-index ≥71.9). Limitation: Patients were drawn from academic centers and analyzed retrospectively. Conclusion: The GAP models use commonly measured clinical and physiologic variables to predict mortality in patients with IPF. Primary Funding Source: University of California, San Francisco Clinical and Translational Science Institute.
FL118, a novel camptothecin derivative, is insensitive to ABCG2 expression and shows improved efficacy in comparison with irinotecan in colon and lung cancer models with ABCG2-induced resistance
Authors: David Westover, Xiang Ling, Hong Lam, Jacob Welch, Chunyang Jin, Celine Gongora, Maguy Del Rio, Mansukh Wani, Fengzhi Li
Journal: Molecular Cancer (2015)

Irinotecan is a camptothecin analogue currently used in clinical practice to treat advanced colorectal cancer. However, acquired resistance mediated by the drug efflux pump ABCG2 is a recognized problem. We reported on a novel camptothecin analogue, FL118, which shows anticancer activity superior to irinotecan. In this study, we sought to investigate the potency of FL118 versus irinotecan or its active metabolite, SN-38, in both in vitro and in vivo models of human cancer with high ABCG2 activity. We also sought to assess the potency and ABCG2 affinity of several FL118 analogues with B-ring substitutions. Colon and lung cancer cells with and without ABCG2 overexpression were treated with FL118 in the presence and absence of Ko143, an ABCG2-selective inhibitor, or alternatively by genetically modulating ABCG2 expression. Using two distinct in vivo human tumor animal models, we further assessed whether FL118 could extend time to progression in comparison with irinotecan. Lastly, we investigated a series of FL118 analogues with B-ring substitutions for ABCG2 sensitivity. Both pharmacological inhibition and genetic modulation of ABCG2 demonstrated that, in contrast to SN-38, FL118 was able to bypass ABCG2-mediated drug resistance. FL118 also extended time to progression in both in vivo models by more than 50% compared with irinotecan. Lastly, we observed that FL118 analogues with polar substitutions had higher affinity for ABCG2, suggesting that the nonpolar nature of FL118 plays a role in bypassing ABCG2-mediated resistance. Our results suggest that in contrast to SN-38 and topotecan, FL118 is a poor substrate for ABCG2 and can effectively overcome ABCG2-mediated drug resistance. Our findings expand the uniqueness of FL118 and support continued development of FL118 as an attractive therapeutic option for patients with drug-refractory cancers resulting from high expression of ABCG2.
Apoptosis of human intestinal epithelial cells after bacterial invasion.
Authors: J M Kim, L Eckmann, T C Savidge, D C Lowe, T Witthöft, M F Kagnoff
Journal: Journal of Clinical Investigation (1998)

Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to undergo apoptosis following infection with invasive enteric pathogens, such as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse monocyte-macrophage cell lines, the commitment of human intestinal epithelial cell lines to undergo apoptosis is delayed for at least 6 h after bacterial infection, requires bacterial entry and replication, and the ensuing phenotypic expression of apoptosis is delayed for 12-18 h after bacterial entry. TNF-alpha and nitric oxide, which are produced as components of the intestinal epithelial cell proinflammatory program in the early period after bacterial invasion, play an important role in the later induction and regulation of the epithelial cell apoptotic program. Apoptosis in response to bacterial infection may function to delete infected and damaged epithelial cells and restore epithelial cell growth regulation and epithelial integrity that are altered during the course of enteric infection. The delay in onset of epithelial cell apoptosis after bacterial infection may be important both to the host and the invading pathogen since it provides sufficient time for epithelial cells to generate signals important for the activation of mucosal inflammation and concurrently allows invading bacteria time to adapt to the intracellular environment before invading deeper mucosal layers.
COX Inhibitors and Thromboregulation
Authors: Aaron J Marcus, M Johan Broekman, David J Pinsky
Journal: New England Journal of Medicine (2002)

Prostacyclin inhibits platelets and dilates blood vessels, whereas thromboxane A2 activates platelets and constricts vessels. In mice lacking receptors for prostacyclin, intimal injury provokes a severe reaction within the artery, whereas in mice lacking thromboxane A2 receptors the response is subdued. These findings are relevant to clinical concerns that cyclooxygenase-2 inhibitors, which specifically impair the formation of prostacyclin, may increase susceptibility to cardiovascular events. Aspirin, which inhibits both prostacyclin and thromboxane A2, protects against arterial thrombosis.