tbuckley/cabot-search huggingface dataset:
Reversal of Hepatic Fibrosis — Fact or Fantasy?
Authors: Scott L. Friedman, Meena B. Bansal
Journal: Hepatology (2006)

The prospect of reversing hepatic fibrosis has generated great interest now that basic science advances are being translated into promising new antifibrotic therapies. It is appropriate to recognize both the historical advances that created the framework for these successes, and the important role that Hepatology has played in disseminating them. A sense of urgency underlies this effort as the epidemics of HCV and NASH are becoming associated with advancing fibrosis. To maintain progress and minimize confusion among investigators and clinicians it is essential to standardize terms referring to fibrosis 'reversal' and 'regression.' There must also be rapid optimization of non-invasive markers of fibrosis to relieve this current bottleneck to conducting clinical trials. Progress in identifying genetic determinants of fibrosis could further refine patient selection for clinical trials and shorten their duration, as well as unearthing new directions of scientific inquiry. Realistic expectations for successful anti-fibrotic therapies reflect solid evidence of fibrosis regression in patients treated effectively for viral liver disease, as well as growing clarity in the understanding mechanisms of extracellular matrix production and degradation. The paradigms of stellate cell activation and apoptosis remain valuable frameworks for understanding pathways of hepatic fibrogenesis and fibrosis regression, respectively. Continued progress is essential in order to identify the determinants and dynamics of fibrosis reversibility, to discover additional targets for anti-fibrotic therapy, and to develop customized multi-drug regimens. These advances are sure to be captured in the next 25 years by Hepatology , and to profoundly impact the prognosis of patients with chronic liver disease.
Variability of house dust mite allergen exposure in dwellings.
Authors: T Hirsch, E Kuhlisch, W Soldan, W Leupold
Journal: Environmental Health Perspectives (1998)

The variability of repeated house dust mite (HDM) allergen determinations at the same site within 3-24 months was evaluated on previously collected samples. Between two and four repeated measurements of Der p 1, a major allergen of Dermatophagoides pteronyssinus and Der f 1, a major allergen of D. farinae, on 46 carpets and 31 mattresses were analyzed. In 90% of carpets and mattresses, HDM allergen concentrations were clinically relevant (at least one measurement >0.1 microg Der p 1 + Der f 1/g dust). The coefficients of variation (CVs) for allergen concentrations in repeated samples over time (55.3-82.0% for the two allergens in beds and carpets) were clearly greater than the CVs for multiple samples collected at the same time (4.0-32.6%). Determination of allergen mass per square meter of surface instead of concentration per gram of dust resulted in an even greater CV (72.3-86.7%). The 95% range of expected values was about 10-fold above and below the result of a single determination. We conclude that single determinations of HDM allergen in dust give very limited information about long-term exposure of an individual to the allergen. Repeated measurements are recommended. Studies of factors that affect HDM allergen exposure must be planned with appropriate sample sizes.
Methotrexate-Induced and Epstein–Barr Virus-Associated B-Cell Lymphoma of the Spine
Authors: Ba D. Nguyen, Michael C. Roarke, Ann E. McCullough
Journal: Clinical Nuclear Medicine (2008)

Methotrexate, used as a disease-modifying agent in the treatment of rheumatoid arthritis and other connective tissue diseases, may depress the immune system and increase the already high risk of Epstein–Barr virus infection in this immune-challenged patient population. The combined impact of methotrexate and Epstein–Barr virus may induce lymphoproliferative disorders involving skin, lung, nodes and central nervous system. The authors present a case of dermatomyositis with methotrexate-related and Epstein–Barr-associated thoracic spinal and paraspinal diffuse large B-cell lymphoma.
ES6-1: Oncofertility: Translation in Multiple Dimensions.
Authors: TK Woodruff
Journal: Cancer Research (2011)

Abstract Cancer is now a disease with a variety of treatment options, which are leading to longer and more productive lives by survivors. Globally, there are 10 million people diagnosed with cancer. 10% of these newly diagnosed men and women are under the age of 45 years old. Infertility can be a consequence of many of the more aggressive chemo- and radiation therapies that prolong and save lives. The ability to easily preserve sperm prior to cancer treatment provides hope at the time of diagnosis and families later in life for male survivors. A notable example is Tour de France winner Lance Armstrong who has three children conceived using sperm frozen days before he underwent the massive chemo- and radiation therapy that saved his life. Unlike sperm, the female germ cell, the oocyte or egg must be retrieved surgically. Moreover, the vast majority of collected oocytes will be immature and cannot be used immediately by a woman who is ready to start a family. The overall hypothesis of the program is that effective fertility-extending options can be provided to young women undergoing life-preserving cancer treatment. The purpose of our work is to bring physicians, medical ethicists, social scientists and basic scientists together to develop new strategies for fertility preservation for female cancer survivors under the new discipline of oncofertility. At the basic science level, complex issues of ovarian function and preservation must be addressed including the problem of follicle growth and development in vitro. Our investigative group has developed a 3-dimensional system that supports follicle development, largely, we believe, because the links between the oocyte and its surrounding cells are maintained. The goal of our program and the broader Oncofertility Consortium is to explore and expand the reproductive options available to young people facing a fertility-threatening but life-preserving cancer treatment. This work is supported by NIH/NICHD Structure-Function Relationships in Reproductive Science, U54 HD041857; and, the Oncofertility Consortium, UL1DE019587 and RL1HD05829 http://oncofertility.northwestern.edu/ Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES6-1.
Pharmacoeconomics: Is a Drug Worth Its Cost?
Authors: Charles Marwick
Journal: JAMA (1994)

THE PRICE is right, the cost is reasonable, but in tomorrow's medical practice what will count is the effectiveness of the intervention in relation to the cost of providing it. A whole new science is springing up that is engaged in developing appropriate standards and ways to evaluate such efficacy from a drug or medical service, say those in this emerging field of pharmacoeconomics. "You can bet your boots that in the next 4 or 5 years this is going to be a major issue because it has to do with health reform and cost control efforts," says Clyde Thornsberry, PhD, of the Microbiology Reference Library, Franklin, Tenn. Thornsberry spoke at the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, held in Orlando, Fla. At future meetings the group plans to hold more sessions on cost-effectiveness studies. <h3>`Where the Money Is'</h3> At the moment, the effort is limited largely to
What To Do When the Risk Environment Is Rapidly Shifting and Heterogeneous? Anticipatory Governance and Real-Time Assessment of Social Risks in Multiply Marginalized Populations Can Prevent IRB Mission Creep, Ethical Inflation or Underestimation of Risks
Authors: Vural Ozdemir
Journal: The American Journal of Bioethics (2009)

Click to increase image sizeClick to decrease image size Acknowledgment The views expressed in the commentary are entirely the personal opinions of the author. The work in this manuscript is supported by an ethics operating catalyst grant from the Canadian Institutes of Health Research (CIHR) and a career investigator salary for science and society research from the Fonds de la Recherche en Santé du Québec (FRSQ). The figure was conceived by Ozdemir and drawn as an illustration by the Montreal based artist Debbie Geltner.
Effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy: pressure-volume analysis with a nonimaging scintillation probe.
Authors: R O Bonow, H G Ostrow, D R Rosing, R O Cannon, L C Lipson, B J Maron, K M Kent, S L Bacharach, M V Green
Journal: Circulation (1983)

To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0.17 to 0.72 mg/kg). Percent change in radionuclide stroke counts after verapamil correlated well with percent change in thermodilution stroke volume (r = .87), and changes in diastolic and systolic counts were used to assess relative changes in left ventricular volumes after verapamil. Verapamil produced dose-related increases in end-diastolic counts (19 +/- 9% increase; p less than .001), end-systolic counts (91 +/- 54% increase; p less than .001), and stroke counts (7 +/- 10% increase; p less than .02). This was associated with a decrease in ejection fraction (83 +/- 8% control, 73 +/- 10% verapamil; p less than .001) and, in the 10 patients with left ventricular outflow tract gradients, a reduction in gradient (62 +/- 27 mm Hg control, 32 +/- 35 mm Hg verapamil; p less than .01). The end-systolic pressure-volume relation was shifted downward and rightward in all patients, suggesting a negative inotropic effect. In 10 patients, left ventricular pressure-volume loops were constructed with simultaneous micromanometer pressure recordings and the radionuclide time-activity curve. In five patients, verapamil shifted the diastolic pressure-volume curve downward and rightward, demonstrating improved pressure-volume relations despite the negative inotropic effect, and also increased the peak rate of rapid diastolic filling. In the other five patients, the diastolic pressure-volume relation was unaltered by verapamil, and increased end-diastolic volumes occurred at higher end-diastolic pressures; in these patients, the peak rate of left ventricular diastolic filling was not changed by verapamil. The negative inotropic effects of intravenous verapamil are potentially beneficial in patients with hypertrophic cardiomyopathy by decreasing left ventricular contractile function and increasing left ventricular volume. Verapamil also enhances left ventricular diastolic filling and improves diastolic pressure-volume relations in some patients despite its negative inotropic effect.
The impact of novel tests for tuberculosis depends on the diagnostic cascade
Authors: Amanda Y. Sun, Claudia M. Denkinger, David W. Dowdy
Journal: European Respiratory Journal (2014)

To the Editor: 

At least 3 million people with active tuberculosis (TB) are missed by national systems every year. Reaching these individuals is a critical priority [1]. Novel molecular diagnostics, notably Xpert MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) [2, 3], are important tools in this effort. Over 6 million Xpert cartridges have been procured worldwide since late 2010 [4] but two recent randomised trials in southern Africa [5, 6] suggest that Xpert, despite high sensitivity, may not significantly reduce morbidity and mortality. It is therefore useful to demonstrate how TB diagnostics function not in isolation but rather as part of a “diagnostic cascade.”

We therefore adapted a transmission model of diagnostic testing among adults with active TB in Southeast Asia [7]. This model categorises a high-burden population into subpopulations characterised by TB status, HIV status and access to TB care. Parameter values, available in the original publication, are consistent with other published models of TB [8, 9]. For transparency, in this analysis, we did not consider multidrug-resistant TB, public/private sector differences or urban/rural differences.

We modelled TB diagnosis as a series of care-seeking attempts occurring after a “pre-diagnostic” delay. Depending on the diagnostic test sensitivity, probability of empirical treatment and efficacy of therapy, each attempt ended either in recovery or return to the active infectious state. Our primary outcomes were 10-year reductions in TB incidence and mortality if TB were diagnosed using Xpert (implemented immediately and fully throughout the population) versus sputum smear microscopy.

We fitted model parameters at the steady state to epidemiological data in India, including life expectancy (66 years [10]), adult …
Detecting congenital heart disease prenatally.
Authors: G. C. Smith
Journal: BMJ (1992)

24 10O.'The difference between this figure and the estimate quoted in my editorial is attributable to the inclusion of additional charges for extended acute hospital care and different assumptions about the life expectancy of survivors (5 v 10 years).Even so, the cost of HA-lA still compares favourably with that of many other widely accepted medical mterventions.
Diagnosing Asthma
Authors: Andrew D. Smith, Jan O. Cowan, Sue Filsell, Chris McLachlan, Gabrielle Monti-Sheehan, Pamela Jackson, D. Robin Taylor
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

International guidelines recommend a range of clinical tests to confirm the diagnosis of asthma. These focus largely on identifying variable airflow obstruction and responses to bronchodilator or corticosteroid. More recently, exhaled nitric oxide (FE(NO)) measurements and induced sputum analysis to assess airway inflammation have been highlighted. However, to date, no systematic comparisons to confirm the diagnostic utility of each of these methods have been performed. To do so, we investigated 47 consecutive patients with symptoms suggestive of asthma, using a comprehensive fixed-sequence series of diagnostic tests. Sensitivities and specificities were obtained for peak flow measurements, spirometry, and changes in these parameters after a trial of steroid. Comparisons were made against FE(NO) and sputum cell counts. Sensitivities for each of the conventional tests (0-47%) were lower than for FE(NO) (88%) and sputum eosinophils (86%). Overall, the diagnostic accuracy when using FE(NO) and sputum eosinophils was significantly greater. Results for conventional tests were not improved, using a trial of steroid. We conclude that FE(NO) measurements and induced sputum analysis are superior to conventional approaches, with exhaled nitric oxide being most advantageous because the test is quick and easy to perform.
Treating fissure in ano in outpatients: what dose of local anaesthetic?
Authors: R T Diggory, E P Simkin
Journal: BMJ (1984)

may represent an absence of vascular response to ketanserin at the latter site but could be due to technical problems of using this method to assess circulation in sclerodermatous skin.The results of ketanserin treatment for ulceration in scleroderma appear to be less favourable than the results in treating Raynaud's pheno-
Therapeutic Efficacy of G207, a Conditionally Replicating Herpes Simplex Virus Type 1 Mutant, for Gallbladder Carcinoma in Immunocompetent Hamsters
Authors: Kenji Nakano, Tomoki Todo, Kazuo Chijiiwa, Masao Tanaka
Journal: Molecular Therapy (2001)

Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 × 107 pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.
Reforming Physician Payment
Authors: Allan H. Goroll
Journal: New England Journal of Medicine (2008)

The editors asked several experts to share their perspectives on the crisis in U.S. primary care. Their articles, which address this crisis from six different angles, follow. We also brought the five U.S. contributors together for a roundtable discussion of the problems and potential solutions for training, practice, compensation, and systemic change. A video of the discussion and reader comments can be seen at www.nejm.org.At the heart of the decline in primary care lie dysfunctional payment systems, from the “gatekeeper” schemes of the 1990s to the current volume-driven, fee-for-service approaches. These have proved antithetical to the goals of primary care, leaving patients unhappy, physicians demoralized, a generation of U.S. medical students shunning careers in the field, and access to care increasingly problematic — all contributing to an impending national health care crisis.1 Several payment reforms have been proposed. One approach would augment fee for service with a “management fee” to pay for coordination of care extending beyond face-to-face encounters. This evolutionary approach, while recognizing . . .
Prophylactic Antibiotics in Surgery
Authors: Andrew M. Munster, Jonathan Weiner, Geoffrey Gibson
Journal: JAMA (1979)

A survey of prophylactic antibiotic-prescribing habits among chiefs of surgical services of the Veterans Administration yielded a 99% response. These responses have been compared with guidelines set by an expert committee on antimicrobial use for the VA central office. Assuming that 100% concordance with the standards of the committee is a desired state, the average hospital is approximately one third away from this goal (average score, 62.4%). The majority of errors were those of overuse rather than underuse. The size of the service and the existence of a university affiliation had no influence on the results. Feedback to the chiefs of service regarding the use of antibiotics was informal and tended to be carried out on rounds rather than as a result of formal audits. Most senior surgeons indicated that they would be willing to be influenced by audit guidelines. (<i>JAMA</i>241:717-718, 1979)
Hunterdon: The Rise and Fall of a Medical Camelot
Authors: Lloyd B. Wescott
Journal: New England Journal of Medicine (1979)

BETWEEN the spring of 1977 and the fall of 1978, an astonishing amount of attention was focused on the dispute between the specialist staff at Hunterdon Medical Center and its board of trustees. During that time, approximately 175 articles on this subject appeared in newspapers, including the New York Times and the New York Daily News, and 24 reports appeared in medical journals. Why did this tempest in a rural New Jersey hospital create so much interest? Obviously, the issues were important.The confrontation turned on the issue of the closed hospital-based specialist staff, which had been a key . . .
Familial brachioradial pruritus
Authors: J. Wallengren, K. Dahlback
Journal: British Journal of Dermatology (2005)

The cause of brachioradial pruritus (a localized itching on the arms or shoulders) is controversial. A hereditary form of this condition has not been reported.To describe the occurrence of brachioradial pruritus in several members of one family.The pedigree of the three generations and the history of brachioradial pruritus was outlined. Four sisters were investigated by radiography of the cervical spine.Five sisters and one brother, together with five of their daughters suffered from recurring brachioradial pruritus. The sisters had had occupations requiring heavy lifting, spent much time outdoors and exposed themselves extensively to the sun. Several complained of neck pain and cervical radiographs of four of them indicated arthrosis.Spinal disease alone cannot explain the symptoms of brachioradial pruritus, which in our patients was characterized by symptom-free periods broken off by relapse late in the summer each year. The pedigree suggests this hereditary form of brachioradial pruritus to be dominant and possibly X-linked.
Primary Malignant Pericardial Mesothelioma Mimicking Pericardial Metastasis from Adenocarcinoma
Authors: Masafumi Horie, Satoshi Noguchi, Wakae Tanaka, Hisanao Yoshihara, Masaki Kawakami, Masaru Suzuki, Yoshio Sakamoto, Teruaki Oka
Journal: Journal of Thoracic Oncology (2010)
Massive Fat Embolism Following Fracture of the Femur: Complete Recovery
Authors: B. S. S. Acharya, J. R. Wilson
Journal: BMJ (1953)

A panel of murine B lymphoma cell lines, which express different levels of Fas, was extensively studied for sensitivity to Fas-mediated death signals via an anti-Fas mAb and Fas ligand-bearing cell lines. Expression of the Fas receptor on the B lymphoma cell lines did not correlate with their capacity to undergo Fas-mediated apoptosis. Moreover, Fas-associated death domain protein recruitment to the death-inducing signaling complex (DISC) complex occurred in all cell lines expressing Fas, regardless of whether they were sensitive to Fas-mediated death. Interestingly, the protein synthesis inhibitor, cycloheximide, and protein kinase C inhibitors, such as bisindolylmaleimide, rendered one of the resistant cell lines, CH33, sensitive to signals from the Fas receptor, although the levels of Fas were unchanged. This suggests that constitutive PKC activation plays a role in Fas resistance, perhaps by up-regulating NF-κB or Bcl-2 family members. Interestingly, CH33 demonstrated caspase 8 activity upon engagement of the Fas receptor in the absence of pharmacological manipulation, suggesting that the block in apoptosis is downstream of the DISC complex. In contrast, the fact that Fas-associated death domain protein was recruited to the DISC complex in other resistant lines, such as WEHI-231, with no caspase 8 activation indicates that these cells may be blocked within the DISC complex. Indeed, Western blot analysis showed that WEHI-231 expressed an isoform of FLICE-like inhibitory protein (cFLIP<sub>L</sub>), an antiapoptotic protein within the DISC. These studies provide evidence that murine B lymphoma cells utilize different molecular mechanisms along the Fas-signaling cascade to block apoptosis.
PHILADELPHIA PLAN FOR HOME CARE OF CHRONICALLY ILL PERSONS
Authors: Louis Udell
Journal: JAMA (1953)

A home care program differing in concept and method from others more generally known has been in operation in a section of Philadelphia since 1949, under the aegis of the Visiting Nurse Society of Philadelphia. This program, officially known as the Intensive Home Care Plan for the Chronically Ill, is based on medical care rendered by the family physician practicing in the community, in contrast to plans in which medical care is given by staff physicians of the hospital from which the patient has been discharged. The purpose of the plan is to give the chronically ill, home-bound patient better and more complete medical care in his own home, using the team cooperation approach and always keeping him under the direct supervision of his private physician. It was designed to permit the participating hospitals to use their beds to better advantage by the discharge of patients who no longer need