tbuckley/cabot-search huggingface dataset:
Prevalence of Calcified Meniscal Cartilage in Elderly Persons
Authors: Jack Bocher, Henry J. Mankin, Robert N. Berk, Gerald P. Rodnan
Journal: New England Journal of Medicine (1965)

SINCE 1933 sporadic reports have described roentgenographically evident calcification of the articular cartilage and menisci,1 2 3 4 5 6 7 8 but in the last two years this finding has received considerable attention as a cardinal, if not pathognomonic, feature of a condition known as chondrocalcinosis articularis or pseudogout. This syndrome, first described by Zitnan and Sitaj9 in 1960, is manifested by episodes of acute monoarticular inflammation of the larger joints that are in many ways similar to that encountered in gout.10 11 12 Although hyperuricemia is occasionally present the syndrome is differentiated from true gout by the finding of crystals of calcium pyrophosphate in aspirated synovial fluid . . .
P233 Cough swabs should not be used to exclude non-tuberculous mycobacterial (NTM) infection in adults with cystic fibrosis
Authors: C Brown, J Choyce, N Rodgers, R Rashid, JL Whitehouse, EG Smith, EF Nash
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> People with cystic fibrosis (CF) are prone to airway infection with non-tuberculous mycobacteria (NTM) including <i>M. abscessus</i>, <i>M. avium</i> and <i>M. intracellulare</i>. Routine NTM screening is recommended for all patients at least once a year.<sup>1</sup> In patients not able to produce sputum, cough swabs are often sent for NTM analysis. Anecdotally, we observed that several patients cared for in our centre had cultured NTM in sputum having previously been culture-negative from cough swabs. The objective of this observational study was to examine the diagnostic yield of cough swabs and sputum samples from CF adults with known NTM infection. <h3>Methods</h3> We identified all CF patients being cared for in our large regional adult CF centre that had cultured any NTM species from cough swabs or sputum samples and are currently attending our NTM clinic. Demographics, clinical parameters and microbiology results were recorded and analysed. <h3>Results</h3> 26 patients (19 male) were included: median age 24 years, 92% chronically infected with <i>P. aeruginosa</i>, 100% pancreatic insufficient, 62% CF-related diabetes, 27% ABPA. 381 sputum samples and 55 cough swabs were analysed. 251 (66%) sputum samples and 4 (7%) cough swabs cultured NTM (see Table 1). In the 4 cough swabs that cultured NTM, sputum samples also cultured the same species. <h3>Conclusions</h3> Cough swabs have a very low diagnostic yield and their use did not contribute to identification of NTM infection in our adult CF patient population. We have therefore stopped sending cough swabs for NTM culture in our centre and our data suggests that cough swabs should not be used to screen for these organisms. <h3>Reference</h3> 1 <i>Mycobacterium abscessus</i> Suggestions for infection prevention and control. CF Trust, 2013
Coronary Thrombosis and Major Bleeding After PCI With Drug-Eluting Stents
Authors: Usman Baber, Roxana Mehran, Gennaro Giustino, David J. Cohen, Timothy D. Henry, Samantha Sartori, Cono Ariti, Claire Litherland, George Dangas, C. Michael Gibson, Mitchell W. Krucoff, David J. Moliterno, Ajay J. Kirtane, Gregg W. Stone, Antonio Colombo, Alaide Chieffo, Annapoorna S. Kini, Bernhard Witzenbichler, Giora Weisz, Philippe Gabriel Steg, Stuart Pocock
Journal: Journal of the American College of Cardiology (2016)
UK scientists would lose money and influence under “Brexit,” says Lords report
Authors: Nigel Hawkes
Journal: BMJ (2016)

Leaving the European Union would cost UK scientists money and influence, says a report by the House of Lords Science and Technology Committee.1

Research funding is one of the few areas where the United Kingdom gains more money than it spends. Of the country’s gross contribution to the EU, £5.4bn (€6.84bn; $7.77bn) can be attributed to the community’s research, development, and innovation activities. But the UK gets back £8.8bn in research grants, so exiting the EU would in theory leave a gap of £3.4bn to be filled.

When total contributions and receipts are counted, the UK is a net loser, contributing £77.7bn a year and getting £47.5bn back. Leaving the EU would therefore save the UK £30.2bn a year, some of which could be …
Outcomes in Patients with Acute Non–Q-Wave Myocardial Infarction Randomly Assigned to an Invasive as Compared with a Conservative Management Strategy
Authors: William E. Boden, Robert A. O'Rourke, Michael H. Crawford, Alvin S. Blaustein, Prakash C. Deedwania, Robert G. Zoble, Laura F. Wexler, Robert E. Kleiger, Carl J. Pepine, David R. Ferry, Bruce K. Chow, Philip W. Lavori
Journal: New England Journal of Medicine (1998)

Non–Q-wave myocardial infarction is usually managed according to an "invasive" strategy (i.e., one of routine coronary angiography followed by myocardial revascularization).
Secondary Cancers after Bone Marrow Transplantation for Leukemia or Aplastic Anemia
Authors: Robert P. Witherspoon, Lloyd D. Fisher, Gary Schoch, Paul Martin, Keith M. Sullivan, Jean Sanders, H. Joachim Deeg, Kristine Doney, David Thomas, Rainer Storb, E. Donnall Thomas
Journal: New England Journal of Medicine (1989)

To determine the incidence of secondary cancers after bone marrow transplantation, we reviewed the records of all patients at our center who received allogeneic, syngeneic, or autologous transplants for leukemia (n = 1926) or aplastic anemia (n = 320). Thirty-five patients were given a diagnosis of secondary cancer between 1.5 months and 13.9 years (median, 1.0 year) after transplantation. Sixteen patients had non-Hodgkin's lymphomas, 6 had leukemias, and 13 had solid tumors (including 3 each with glioblastoma, melanoma, and squamous-cell carcinoma). There were 1.2 secondary cancers per 100 exposure-years during the first year after transplantation (95 percent confidence interval, 0.7 to 2.0). The rate declined to 0.4 (95 percent confidence interval, 0.2 to 0.7) after one year. The age-adjusted incidence of secondary cancer was 6.69 times higher than that of primary cancer in the general population. In a multivariate model, the predictors (and relative risks) of any type of secondary cancer were acute graft-versus-host disease treated with either antithymocyte globulin (relative risk, 4.2) or an anti-CD3 monoclonal antibody (13.6) and total-body irradiation (3.9). Two additional factors were associated with secondary non-Hodgkin's lymphomas: T-lymphocyte depletion of donor marrow (12.4) and HLA mismatch (3.8). We conclude that recipients of bone marrow transplantation have a low but significant risk of a secondary cancer, particularly non-Hodgkin's lymphoma. (N Engl J Med 1989; 321:784–9.)
Hemodynamic Characterization of Tolerance to Long-Term Hydralazine Therapy in Severe Chronic Heart Failure
Authors: Milton Packer, Jose Meller, Norma Medina, Madeline Yushak, Richard Gorlin
Journal: New England Journal of Medicine (1982)

We performed hemodynamic studies in 11 patients with severe chronic heart failure whose symptoms had returned to their pretreatment status after 37±15 weeks (mean ±S.E.M.) of therapy with the vasodilator hydralazine. The cardiac index increased from 1.85 to 3.47 liters per minute per square meter of body-surface area, and systemic vascular resistance decreased from 1748 to 754 dyn · sec · cm-5 (both P<0.01) during initial hydralazine administration but returned to pretreatment values on repeat evaluation; withdrawal of the drug produced no hemodynamic deterioration. Responsiveness to hydralazine could not be restored by doubling the oral dose or by intravenous administration; tolerance was associated with fluid retention in five patients but was not reversed by intensive diuresis. In contrast, the responses to nitroprusside evaluated before and after the development of hydralazine tolerance were unaltered; other oral vasodilators were still effective. We conclude that drug-specific tolerance may account for the lack of clinical improvement in some patients with severe heart failure who receive long-term treatment with hydralazine. (N Engl J Med. 1982; 306:57–62.)
Abstract 19783: The Impact of Cardiac Sympathetic Nerve Activity Evaluated by Cardiac I-123 Metaiodobenzylguanidine Scintigraphy on the Chronotropic Incompetence
Authors: Toshihiko Goto, Kazuaki Wakami, Kento Mori, Kenta Hachiya, Noriyuki Ikehara, Hiroshi Fujita, Hidekatsu Fukuta, Nobuyuki Ohte
Journal: Circulation (2015)

Introduction: Chronotropic incompetence (CI), defined as the inability of the heart to increase its rate commensurate with increased activity, produces exercise intolerance, and is an independent predictor of overall mortality. Cardiac sympathetic nerve (SNS) activity has been suggested to have a relation to CI. However, the mechanisms for CI have not been fully elucidated. Thus, we investigated the cardiac SNS activity in patients with CI using cardiac I-123 metaiodobenzylguanidine (MIBG) scintigraphy. Methods: Sixteen patients with CI and 17 subjects who served as controls were enrolled in this study (age 77.5±9.2years; male 57.6%). Patients with CI were defined as who were implanted with pacemaker due to sick sinus syndrome. Results: There were no significant differences in age, sex, or left ventricular ejection fraction (66.3±14.3 vs 58.3±22.2%, ns) between patients with CI and controls. Plasma BNP level was also similar between two groups (79.0[IQR, 41.0-175.3] vs 90.9[IQR, 35.5-185.3]pg/mL, ns). The delayed heart/mediastinum (H/M) ratio was significantly higher in patients with CI than in controls (2.3±0.3 vs 2.0±0.4%, p=0.04). The early H/M ratio did not differ between two groups. The washout rate (WR) was significantly lower in patients with CI compared with that in controls (20.2±11.2 vs 33.3±14.1%, p=0.006). Conclusions: Decreased cardiac sympathetic nerve activity was associated with CI, and I-123 MIBG scintigraphy may be a useful modality for understanding the mechanism for CI.
Under-Expression of LINE-1 Retrotransposons in Chronic Myeloid Leukemia Patients: Effect of Tyrosine Kinase Inhibitors
Authors: Beatrice Turcq, Marina Josselin, Kelly Airiau, Stéphanie Dulucq, Gabriel Etienne, Francis Belloc, Fabienne Hermitte, Francois-Xavier Mahon
Journal: Blood (2014)
Utility of Histone deacetylase 6, a novel estrogen regulated gene affecting cell motility, as predictive factor for adjuvant endocrine treatment and as therapeutic target
Authors: S. Saji, M. Kawakami, S.-I. Hayashi, S.-I. Horiguchi, M. Yoshida, S. L. Schreiber, M. Toi
Journal: Journal of Clinical Oncology (2005)

641 Background: The expression of estrogen-regulated genes (ERGs) in breast cancer is thought to indicate the presence of an active estrogen signaling pathway via estrogen receptor (ER). We performed screening micro array analysis in MCF-7 cells, and one of these ERGs, histone deacetylase 6 (HDAC6), which recently appeared to deacetylate α-tubulin and affects cell motility, was chosen for further analysis. Methods: 139 consecutive breast cancer samples obtained by surgery from 1992–94 was evaluated based on the expression of HDAC6 by immunohistochemistry, and analyzed for correlation with disease free and overall survivals by log rank tests. Western blotting was used for evaluation of expression of HDAC6, α-tubulin, acetylated α-tubulin. Stable cell clones with HDAC6 expression vector were established, and transwell migration assay was used for cell motility evaluation. Results: Prognostic analysis of 139 samples revealed no significant differences based on HDAC6 expression. However, subset analysis with ER-positive patients showed that there was a statistically significant difference in relapse free survival (RFS) and favorable profile for the positive HDAC6 group in overall survival (OS) (n=82, p<0.05 and p=0.06 in RFS and OS, respectively). The power of prediction became more remarkable for those receiving adjuvant treatment with tamoxifen for more than 2 years (n=67, p<0.02 and p<0.05 in RFS and OS, respectively). HADC6 expression was significant prognostic factors by multivariate analyses (odds ratio=2.82, p=0.047). Estradiol treatment to MCF-7 increased HDAC6 expression and deacetylated α-tubulin, and showed a 4-fold increase in cell motility. Introduction of HDAC6 expression vector into MCF-7 cells also enhanced cell motility but not affected proliferation. Either the tamoxifen, or ICI 182,780 prevented estradiol-induced HDAC6 accumulation and reverse cell motility in dose-dependent manner. Synthesized small molecule inhibiting catalytic domain of HDAC6 showed synergy with anti-estrogens. Conclusions: Expression HDAC6 predicts the degree of benefit by adjuvant tamoxifen treatment and is also therapeutic target. No significant financial relationships to disclose.
S45 MUC5B Genotype does not influence cough severity in IPF
Authors: P Saunders, CJ Stock, PL Molyneaux, M Kokosi, S Kingston, MG Belvisi, AU Wells, EA Renzoni, TM Maher
Journal: Thorax (2015)

<h3>Introduction</h3> Cough is a disabling symptom in IPF which causes significant reduction in quality of life. The mechanisms underlying cough in fibrotic lung disease are not well understood. Polymorphisms in the rs35105950 promoter region of the <i>MUC5B</i> gene have been shown to relate to risk of developing IPF and, in those with disease, have been shown to increase mucin expression in the small airways. A previous small study linked carriage of the minor T allele at rs35105950 with heightened cough in IPF. We sought to test this observation in a larger cohort of prospectively recruited individuals with IPF. <h3>Method</h3> <i>MUC5B</i> genotyping was performed on 117 prospectively recruited individuals with IPF. All subjects completed the Leicester Cough Questionnaire and full lung function at the time of their blood draw. Survival time from enrolment was censored at 1<sup>st</sup> May 2015. Statistical analyses were performed using SAS software. <h3>Results</h3> The mean age of subjects at enrolment was 68 ± 8.4 with 79% being male. Subjects had, on average, moderately severe disease with mean FVC 73.9 ± 19.7% predicted and DLco 41.7 ± 18.1% predicted. At baseline, the median (IQR) LCQ score was 16.0 (11.6–18.6) points. 43 subjects (36.8%) were homozygous at rs35105950 for the G allele, 62 (53.0%) were heterozygous and 12 (11.1%) were homozygous for the T allele. Despite a trend towards worse disease at baseline, homozygosity of the T allele was correlated with a significant survival advantage (422 days compared to GG, p = 0.0063). There was, however, no difference on univariate analysis in LCQ cough severity between groups based on <i>MUC5B</i> genotype (GG 14.6 ± 4.5, GT 15.3 ± 3.9 and TT 15.1 ± 3.5, p = 0.70). This finding did not change when correction was applied for baseline disease severity. <h3>Conclusions</h3> The severity of self-reported cough is worse in IPF than in other respiratory diseases. In contrast to one previous small study of 68 subjects, there is no relationship between patient reported cough and <i>MUC5B</i> genotype in our cohort. It therefore seems unlikely that the mechanism behind cough in fibrosing lung disease is related to mucin production. Further studies are required to determine the mechanisms underlying the heightened cough response observed in IPF.
DiiA is a novel dimorphic cell wall protein of Streptococcus pneumoniae involved in invasive disease
Authors: María S. Escolano-Martínez, Arnau Domenech, José Yuste, María I. Cercenado, Carmen Ardanuy, Josefina Liñares, Adela G. de la Campa, Antonio J. Martin-Galiano
Journal: Journal of Infection (2016)
Tositumomab and iodine I 131 tositumomab: Efficacy and safety in 141 patients (pts) with previously untreated low-grade (LG) non-Hodgkin’s lymphoma (NHL)
Authors: M. S. Kaminski, M. Coleman, B. K. Link, R. L. Wahl, S. J. Goldsmith, L. Kostakoglu, J. P. Leonard
Journal: Journal of Clinical Oncology (2005)

6560 Background: Tositumomab and Iodine I 131 Tositumomab (the BEXXAR Therapeutic Regimen, hereafter Iodine I 131 Tositumomab) yields high rates of durable and complete (CR) responses in pts with relapsed/refractory LG NHL. Methods: The efficacy and safety of this regimen was reviewed for 141 pts with previously untreated LG NHL in 3 studies: 76 pts receiving Iodine I 131 Tositumomab as stand-alone therapy, 35 pts receiving an abbreviated regimen of 3 cycles of fludarabine followed by Iodine I 131 Tositumomab, and 30 pts receiving 6 courses of CVP followed by Iodine I 131 Tositumomab. Investigator efficacy assessments were used. All responses had to be confirmed by a subsequent response ≥4 weeks later. Median follow-up was 61 mo (range, 8–101 mo). Results: Median age: 49 yr (range, 23–82 yr); median time from NHL dx: 8 mo; stage III/IV: 99%; tumor diameter ≥5 cm: 49%; bone marrow involvement: 55%. Overall response rate was 95% (95% CI: 90%, 98%); CR rate was 77% (95% CI: 69%, 84%). Median progression-free survival (PFS) was 6.1 yr. Only the presence of bone marrow involvement was associated with shorter PFS. Infusions were well tolerated (rate adjustments in only 4% of infusions). Hematologic toxicity was regimen dependent; no pts in the Iodine I 131 Tositumomab single agent study received supportive care vs 28% in the Iodine I 131 Tositumomab combination regimens studies. Nonhematologic non-serious AEs were significantly more frequent in the single agent study (excluding chemotherapy period in combination studies). Overall only 4% of pts had a drug-related serious AE after Iodine I 131 Tositumomab. Elevated HAMA levels occurred in 63% of the pts in the single agent study vs 3% of pts in the combination studies. Hypothyroidism (elevated TSH) occurred in 9% of pts in the single agent study and 10% in the combination studies. Two pts (both from combination studies) developed MDS/AML, with an overall annualized incidence of 0.3%/yr. Conclusions: Iodine I 131 Tositumomab stand-alone therapy and in combination with chemotherapy was well tolerated and resulted in prolonged PFS in pts with previously untreated LG NHL. Randomized comparative studies should be performed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Candidate AIDS Vaccines
Authors: Barney S. Graham, Peter F. Wright
Journal: New England Journal of Medicine (1995)

There is an urgent need to control the global epidemic of human immunodeficiency virus type 1 (HIV-1) infection. Although educational approaches to modify risk-taking behavior are a critical component of prevention, we focus this discussion on the status of vaccine development. The success of active immunization against other infectious diseases makes immunization an attractive approach to preventing HIV-1 infection. The eradication of smallpox1 and progress in the elimination of poliomyelitis, targeted to occur by the year 2000,2 are notable examples of the impact of vaccination.Given the complexity of HIV-1 pathogenesis, however, empirical approaches successful in the development of previous . . .
Effectiveness of Salk Vaccine in Reducing Nonparalytic Poliomyelitis in a Large Urban Epidemic
Authors: William M. Marine, Tom D. Y. Chin, Clifton R. Gravelle, Marjorie E. Soergel
Journal: New England Journal of Medicine (1961)

IN the 1954 field trial with poliomyelitis vaccine1 and in subsequent outbreaks of poliomyelitis2 3 4 5 6 the Salk vaccine was shown to be highly effective in reducing the incidence of paralytic poliomyelitis. Although it might be expected theoretically, evidence for a comparable effectiveness against nonparalytic poliomyelitis was not described.Kansas City, Missouri, had a severe poliomyelitis epidemic in 1959 that was carefully investigated. Etiologic studies were performed in four fifths of the cases. The majority of the reported paralytic and nonparalytic cases were proved to be due to poliovirus Type 1 infection. Other enterovirus infections were associated with the aseptic-meningitis syndrome in . . .
The Increasing Cost of Medical Care: Its Relation to Hospitals and Specialization in Medicine
Authors: George W. Holmes
Journal: New England Journal of Medicine (1945)

THE purpose of this paper is to state briefly the causes that, in my opinion, have led to an increase in the cost of sickness, to review the various attempts that have been made to meet it, and to suggest certain lines of approach that might lead to a solution of the problem.The present high cost of sickness had its beginning in the latter part of the last century, and is due almost entirely to the rapid advances of medical science and the general acceptance of the community hospital instead of the home as the best place for the . . .
Studies on Human Leukemia. II. Structure and Quantitation of Myxovirus-Like Particles Associated With Human Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Kendall O. Smith, Matilda Benyesh-Melnick, Donald J. Fernbach
Journal: JNCI Journal of the National Cancer Institute (1964)

A method was developed (or the quantitation and examination of the morphology of myxovirus-like particles found in human leukemic and infectious mononucleosis materials. The average diameter of particles from leukemic patients was 178 mμ compared with 138 mμ for particles from patients with infectious mononucleosis. Particles from both sources were structurally similar to each other and to particles associated with avian and murine leukemia. However, no tail-like appendages were seen on particles from human specimens like those sometimes seen on particles associated with murine leukemias. Concentrations of over 3 × 1010 particles per ml were encountered in some human sera and plasmas. Normal whole blood cells, on prolonged storage at 4° C, released particles remarkably similar in size and morphology to the particles seen in materials from leukemic and infectious mononucleosis patients.
Detection of Infectious Simian Immunodeficiency Virus in B- and T-Cell Lymphomas of Experimentally Infected Macaques
Authors: Maria Teresa Maggiorella, Francesca Monardo, Martin Luther Koanga-Mogtomo, Livia Cioè, Leonardo Sernicola, Franco Corrias, Carlo David Baroni, Paola Verani, Fausto Titti
Journal: Blood (1998)
Effect of Short-Term Infusion of Sodium Nitroprusside on Mortality Rate in Acute Myocardial Infarction Complicated by Left Ventricular Failure
Authors: Jay N. Cohn, Joseph A. Franciosa, Gary S. Francis, Donald Archibald, Felix Tristani, Ross Fletcher, Alfredo Montero, Guillermo Cintron, Janice Clarke, David Hager, Robert Saunders, Frederick Cobb, Raphael Smith, Henry Loeb, Harold Settle
Journal: New England Journal of Medicine (1982)

Original Article from The New England Journal of Medicine — Effect of Short-Term Infusion of Sodium Nitroprusside on Mortality Rate in Acute Myocardial Infarction Complicated by Left Ventricular Failure — Results of a Veterans Administration Cooperative Study
Estradiol Production after Ovariectomy for Carcinoma of the Breast
Authors: Joseph J. Barlow, Kendall Emerson, Badri N. Saxena
Journal: New England Journal of Medicine (1969)

Measurements of estradiol production rates before and after castration in women with breast cancer indicated that postmenopausal ovaries made no contribution to estrogen production. A review of previous reports of estrogen measurements and of beneficial responses after ovariectomy in postmenopausal women gave little evidence to support the policy of therapeutic castration in such patients with breast cancer. Therapeutic oophorectomy without adrenalectomy is probably not justified in postmenopausal women with breast cancer.