tbuckley/cabot-search huggingface dataset:
Seasonal Prevalence of Upper Respiratory Pathogens
Authors: Henry Stimson Harvey, Marjorie Bodwell Dunlap
Journal: New England Journal of Medicine (1961)

THE study of upper respiratory flora in a group of healthy families has been continued according to the procedure previously described.1 , 2 The particular object of the present analysis was to determine whether seasonal variations occurred in the prevalence of the common potential pathogens, the hemolytic streptococcus, Haemophilus influenzae and the pneumococcus. The material presented here was gathered over a seven-year period, from October, 1953, through September, 1960, with two months omitted in the summer of 1955 and one month omitted in the summer of 1958. It summarizes cultures taken on 556 persons, in 97 family groups.MethodMonthly cultures were . . .
Sensitization of tumor necrosis factor-induced lung cancer cell eath by luteolin
Authors: Wei Ju, Xia Wang, Jordan J. Renouard, Yong Lin
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1371 

Lung cancer is the leading cause of cancer-related death in the United States. Most lung cancer cells are resistant to chemotherapy, the mechanism of which is not well understood. Combinations of multiple anti-cancer drugs may be an effective strategy to improve the efficacy of lung cancer therapy. In this study, we examined the anti-cancer activity of tumor necrosis factor (TNF) combined with the flavonoid luteolin and found that luteolin treatment significantly sensitized lung cancer cells to TNF-induced cell death. The cell death induced by TNF and luteolin treatment is mainly apoptosis, which was detected both morphologically and biochemically. Although luteolin treatment had no effect on the expression levels of the key components of TNF receptor I signaling cascade including TRADD, RIP, TRAF2 and FADD, the TNF-induced NF-κB activation was effectively blocked, which is evidenced by NF-κB reporter assays and Western blots for the expression of NF-κB targeted anti-apoptosis genes. In the NF-κB-disabled cells expressing a non-degradable IκBα mutant (IκBαAA), the synergistic cytotoxicity induced by Luteolin and TNF treatment was abolished, suggesting that the potentiation of TNF-induced cell death by luteolin is achieved by blocking TNF-induced NF-κB activation. The target of the NF-κB pathway by luteolin appears to be downstream of IκB, since treatment with luteolin did not affect the TNF-induced IκBα phosphorylation and degradation. Altered modification of the RelA/p65 subunit of NF-κB in luteolin treated cells was detected, suggesting that modulation of the transcription activity contributes to the blockage of NF-κB by luteolin. In addition, we also found that luteolin augmented the TNF-induced c-Jun N-terminal protein kinase (JNK) activation, and suppression of JNK activity with a specific chemical inhibitor significantly inhibited the synergistic cytotoxicity induced by luteolin and TNF treatment. Thus activation of JNK may also contribute to the potentiation of cell death by luteolin. Taken together, our results suggest that luteolin potentiates TNF-induced lung cancer cell death through blockage of NF-κB and activation of JNK, and the combined treatment with luteolin and TNF could be useful for treating lung cancer.
THU0046 Abatacept Decreases Disease Activity in the Absence of CD4+ T-Cells in the Collagen Induced Arthritis Model
Authors: D. Jansen, H. el Bannoudi, R. Arens, K. Habets, M. Hameetman, T. Huizinga, J. Stoop, R. Toes
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Abatacept is a fusion protein of human CTLA-4 and the Fc portion of human IgG1. It is believed to be effective in the treatment of rheumatoid arthritis by blocking the co-stimulation of T-cells via blocking CD28-B7 interaction as CTLA-4 binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with B7 is crucial for the activation of naïve cells, whereas it is unclear whether the action of already activated CD4+ T-cells, which are readily present in established disease, also depend on this interaction. <h3>Objectives</h3> The aim of this study was to determine whether the mode of action of Abatacept depends on its ability to halt T-cell activation in established disease. <h3>Methods</h3> Arthritis was induced in thymectomized male DBA/1 mice by immunisation with bovine collagen type II. The mice were subsequently depleted for CD4+ T-cells. Abatacept or control treatment was started when 80% of the mice showed signs of arthritis. Arthritis severity was monitored by clinical scoring of the paws and anti-collagen antibody levels over time were determined by ELISA. <h3>Results</h3> Treatment with Abatacept in the absence of CD4+ T-cells resulted in lower disease activity. This was associated with decreasing levels of collagen specific IgG1 and IgG2a antibodies while the antibody levels in control- or CD4+ T-cell-depleted mice increased over time. <h3>Conclusions</h3> These results show that Abatacept decreased disease activity in the absence of CD4+ T-cells indicating that the mode of action of Abatacept in established arthritis does not entirely depend on its effects on CD4+ T-cell activation. <h3>Disclosure of Interest</h3> None declared
Constitutive aryl hydrocarbon receptor signaling constrains type I interferon–mediated antiviral innate defense
Authors: Taisho Yamada, Hiromasa Horimoto, Takeshi Kameyama, Sumio Hayakawa, Hiroaki Yamato, Masayoshi Dazai, Ayato Takada, Hiroshi Kida, Debbie Bott, Angela C Zhou, David Hutin, Tania H Watts, Masahiro Asaka, Jason Matthews, Akinori Takaoka
Journal: Nature Immunology (2016)
Failure of the Peritoneal-Button Operation for Ascites
Authors: Kenneth J. Welch
Journal: New England Journal of Medicine (1947)

THE surgical treatment of patients with recurrent massive ascites that requires frequent abdominal paracentesis has long been a challenging problem. Operative procedures designed to remedy the defect have carried an appreciable mortality, particularly in patients with portal obstruction due to hepatic cirrhosis who develop ascites relatively late in the course of the disease. Such procedures fall into several well defined groups. Some of these are designed merely to rid the patient of an oppressive volume of fluid; others attempt to eliminate factors in the production of ascitic fluid, and still others attempt to improve the body economy by returning water, . . .
Interstitial Myocarditis in Children
Authors: C. G. Tedeschi, Thomas D. Stevenson
Journal: New England Journal of Medicine (1951)

AN increasing number of case reports and some surveys on post-mortem material, showing varying degrees of myocardial involvement more frequently than clinical observation might have led one to suspect, call for a revision of the generally expressed belief that infectious processes of children, with the exception of rheumatic disease and diphtheria, rarely affect the myocardium. Saphir's1 demonstration of 97 cases of myocarditis in 1420 consecutive autopsies in children (6.83 per cent), as compared with 150 instances of myocarditis found during the same period in 3712 autopsies on adults (4 per cent), speaks strongly for the necessity of a deeper inquiry . . .
Effects of breast feeding and overweight on asthma and respiratory symptoms in schoolchildren
Authors: Aya Lafta, Mohammed Shamssain
Journal: European Respiratory Journal (2014)

Very few studies have looked at the long-term effects of breastfeeding. Studies showed an overweight status may negatively affect the activity level among those with asthma or wheeze. The present study is part of a large population study in the United Arab of Emirates (UAE) and Iraq. We studied 1780 schoolchildren from both countries. We used the Arabic and English version of ISAAC questionnaire (the International Study of Asthma and Allergies in Childhood). The prevalence rates of ever wheezed, current wheeze, speech limitation, ever diagnosed with asthma, dry cough, and exercise-induced asthma in children who breastfed 10 months or less were significantly higher than those who breastfed more than 10 months ( 30.7%, 23.6%, 5.4%, 30.8%, 30.0%, and 23.8% vs. 16.5%, 12.6%, 4.8%, 15.7%, 11.2%, and 13.1%, respectively). The prevalence rates of the above symptoms in children with a BMI more than 22 were significantly higher than those with BMI 22 or less (28.2%, 20.3%, 3.0%, 28.1%, 24.2%, and 22.2% vs. 20.4%,17.0%, 2.5%, 19.9%, 16.6%, and 15.2%, respectively). The present study shows that long period of breastfeeding offer more protection from asthma and respiratory symptoms than short period of breastfeeding. Overweight children have significantly higher prevalence rates of asthma and respiratory symptoms than normal weight children. The present study helps to implement intervention strategies to reduce asthma and respiratory symptoms in children.
112P Ethnic differences in presentation of breast cancer patients treated in Hospital Kuala Lumpur, Malaysia
Authors: A. Deniel, N.A. Hakim, N.A. Md Nordin, T.M.I. Tg Abu Bakar Sidik, S. Subramanian, N.D. Kamaruzaman, A.B. Rosc Suzanna
Journal: Annals of Oncology (2015)
Management of the Pregnant Patient with Cardiac Disease
Authors: William Horowitz
Journal: New England Journal of Medicine (1955)

ABOUT seventy-five years ago French physicians followed the dictum: the girl with heart disease should not marry; if married she should not bear children; and if she does bear a child she must not nurse. Today, with a better understanding of the physiologic cardiovascular changes during normal pregnancy, the physician can more properly evaluate and manage each patient so that many women with heart disease may have successful pregnancies.1 , 2 The maternal mortality has fallen largely because of adequate prenatal care, including the education of the patient. Statistics for Bronx County list 19 maternal deaths per 10,000 live births during 1940–1945 . . .
Transplantable ArgyropH&lt;sub&gt;i&lt;/sub&gt;lic Gastric Carcinoid of &lt;italic&gt;Mastomys natalensis&lt;/italic&gt; Secreting Both Histamine and Serotonin
Authors: S Hosoda, K Suzuki, K Sudo, N Yoshida, C Tanaka
Journal: JNCI Journal of the National Cancer Institute (1979)

A transplantable strain of gastric carcinoids of Mastomys (Praomys) natalensis secreted not only histamine but also serotonin [5-hydroxytryptamine (5-HT)]. Mastomys bearing growing transplants excreted 11.3 times more histamine and 4.4 times more 5-hydroxyindole-3-acetic acid (5-HIAA) in the urine than did Mastomys in which transplanted tumors did not grow. Mastomys that developed primary gastric carcinoids also excreted 3.9 times more histamine than did those free from primary tumors, but the difference in urinary excretion of 5-HIAA was not significant in both groups. All transplantable carcinoids contained definite amounts of both histamine and serotonin, whereas the primary gastric carcinoids contained only histamine. We also confirmed that the histamine and 5-HIAA excreted in urine increased as the size of transplanted tumors enlarged. 5-HT was histochemically demonstrated in a small number of carcinoid cells of the transplanted tumors but not in primary carcinoids.
A phase I, pharmacokinetic (PK), and preliminary efficacy assessment of ALD518, a humanized anti-IL-6 antibody, in patients with advanced cancer
Authors: S. J. Clarke, J. T. Smith, C. Gebbie, C. Sweeney, N. Olszewski
Journal: Journal of Clinical Oncology (2009)

3025 Background: ALD518 is a humanized anti-IL-6 antibody being developed for the treatment of cancer cachexia and fatigue. The primary objective of the study was to determine the safety of ALD518. Methods: 9 patients (pts) with advanced cancer, ECOG 0–2, and C-reactive protein (CRP) &gt;10mg/L were enrolled. Pts were assigned to 1 of 3 dose-escalating cohorts (n=3/cohort). ALD518 was given as a single i.v. infusion of 80mg, 160mg, or 320mg. Pts were followed up for 12 weeks. Data included lab safety tests (LSTs), vital signs, ECGs, adverse events, hand grip strength (HGS), FACIT-F, PK and C-reactive protein (CRP). Results: 9 pts were evaluable for dose limiting toxicity (DLT) assessment at week 4 and 5/9 pts completed all visits. Of the 4 pts who failed to complete every visit; 3 were withdrawn due to progressive disease and 1 to be treated with chemotherapy. There were no DLTs or infusion reactions. There were 4 SAEs: 3 disease progressions and 1 sepsis secondary to a blocked biliary stent. There were no grade 3/4 toxicities. Changes in LSTs, CRP, HGS and FACIT-F fatigue subscale (pooled ITT analysis) are shown (Table). Conclusions: ALD518 given to pts with advanced cancer was safe and well tolerated. ALD518 reversed fatigue, increased hemoglobin and albumin, and there was a trend to increased HGS. There was a mild decrease in platelet count that remained stable throughout the study. [Table: see text] [Table: see text]
P215 The Epidemiology of Pneumothorax in England (1968–2011)
Authors: RJ Hallifax, R Goldacre, NM Rahman, M Goldacre
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Spontaneous Pneumothorax (SP) is a common pathology. Incidence rates are quoted as 16–24 and 1.2–6 per 100,000 cases per annum for males and females respectively, based on two studies in single centres (45 years ago, USA; 30 years ago, Sweden) and 4-year periods of national data in UK (1991–4) and France (2008–2011). The aim of this study is to determine the incidence and recurrence of spontaneous pneumothorax in a larger dataset in England. <h3>Methods</h3> An all-England Hospital Episode Statistics (HES) dataset from 1968–2011 was used to determine the incidence of Spontaneous Pneumothorax using International Classification of Diseases codes as the main diagnosis in a hospital admission. A record-linked HES dataset (only available from 1999–2011) was used to distinguish between Primary and Secondary Spontaneous Pneumothorax (PSP and SSP) and to determine the risk of a second pneumothorax within specified time intervals. SSP was defined as the patient having a diagnosis of a chronic lung disease (e.g. COPD, emphysema, lung malignancy, asthma, bronchiectasis, sarcoidosis) made at any time covered by the linked data. <h3>Results and discussion</h3> From 1968–2011, in a population of 50 million, there were a total of 246,534 episodes of spontaneous pneumothorax (no data for 1986–89). In 1999–2011, the average annual incidence was 9.1 per 100,000 males and 3.2 per 100,000 females for PSP; 11.9 and 4.7 for SSP; and 21.0 and 7.9 for SP overall. The incidence of SP appears to be increasing (Figure 1): it was 12.5 (95% confidence interval 12.2–12.8) in 1999 and 13.6 (13.3–13.9) in 2011. It is unclear whether this reflects a true rise in new cases, better reporting or increasing recurrence rates. The overall risk of recurrence is 13.5% within 1 year (18.7% within 5 years). Recurrence is more common in SSP than PSP at 1 year (16.1% vs 10.6%) and 5 years (21.2% vs 14.7%). <h3>Conclusions</h3> This is the largest epidemiological study of pneumothorax to date. These data only cover hospitalised pneumothorax, and therefore may be a conservative estimate of the true burden of disease. Pneumothorax appears to be increasing in incidence.
Dietary fat reduction in postmenopausal women with primary breast cancer: Phase III Women’s Intervention Nutrition Study (WINS)
Authors: R. T. Chlebowski, G. L. Blackburn, R. E. Elashoff, C. Thomson, M. T. Goodman, A. Shapiro, A. E. Giuliano, N. Karanja, M. K. Hoy, D. W. Nixon
Journal: Journal of Clinical Oncology (2005)

10 Background: Despite preclinical and observational studies suggesting benefit, dietary fat influence on breast cancer outcomes has been controversial. Methods: We conducted a randomized trial to test whether an intensive dietary intervention designed to reduce dietary fat intake was effective in influencing relapse-free survival in postmenopausal women with primary breast cancer. A total of 2,437 women with early stage resected breast cancer, 48–79 years old, were randomized within 365 days from surgery in a 40:60 ratio to dietary intervention or control groups at 37 U.S. sites. All received standard breast cancer management: mastectomy or lumpectomy plus radiation; tamoxifen for ER positive, protocol-defined chemotherapy for ER negative and optional chemotherapy for ER positive cases. The dietary intervention included eight bi-weekly individual counseling sessions conducted by centrally trained nutritionists who provided ongoing contacts throughout. Results: Patient characteristics and recurrence risk factors were balanced. Dietary fat intake reduction was greater in the dietary group (fat gram intake/day at 12 months, 33.3 ± 16.7, mean ± standard deviation (SD) versus 51.3 ± 24.4 in controls, respectively, p<0.001). After 60 months median follow-up, the 277 reported relapse events are outlined below by treatment group and receptor status. Conclusion: Life-style intervention resulting in dietary fat intake reduction may improve the relapse-free survival of postmenopausal breast cancer patients. No significant financial relationships to disclose.
PWE-067 Variability in reporting and interpretation of calprotectin levels in the united kingdom
Authors: MJ Brookes, J French, R Logan, C Ford, R Gama, A Robins, S Whitehead, H Steed
Journal: Gut (2015)

<h3>Introduction</h3> Faecal calprotectin (f-Cp), a calcium binding protein, is a product of mucosal granulocyte infiltration in Inflammatory Bowel Disease (IBD). In 2013 NICE supported its use in the UK as a tool for distinguishing between IBS and IBD. However we have previously reported inter-assay variability which may limit the efficacy of this test in IBD and current practice in reporting f-Cp seems to vary across the UK. The aim of this questionnaire was to determine the variability in reporting of f-Cp results to clinicians from laboratories across the UK. <h3>Method</h3> A questionnaire evaluation of all laboratories in the UK who currently perform a f-Cp assay and are members of the national quality assessment programme (UK NEQAS for Faecal Markers of Inflammation). <h3>Results</h3> The questionnaire was sent to 59 laboratories in the UK and responses were received from 69% (n=41). All laboratories performed their own assay on site. The reference ranges varied between laboratories being &lt;50 ug/g in 82.9% (n=34), &lt;60 ug/g in 4.9% (n=2) and other ranges were used by the remainder of laboratories (12.2%; n=5). The reference range was either derived from the commercial supplier in 58.5% (n=24) or by the laboratory locally in 41.5% (n=17). An indeterminate range for f-Cp was provided by only 56.1% (n=23) of laboratories. The reporting of this indeterminate range was however very variable between sites, with the commonest reported range being 50-200 ug/g by 30.4% (n=7) of these laboratories. 70.7% (n=29) of laboratories generated a report which also provided clinical advice. For those laboratories who provided an indeterminate range, only 52.2% (n=12) also provided clinical advice on how to interpret these results. <h3>Conclusion</h3> The normal or reference range for f-Cp across UK laboratories seems to be relatively standardised. However for results outside of the normal reference range there seems to be increasing variability, which is particularly highlighted by the wide practices with regards to interpreting indeterminate results. <h3>Disclosure of interest</h3> None Declared.
Low Platelet 2β1 Levels in Type I von Willebrand Disease Correlate With Impaired Platelet Function in a High Shear Stress System
Authors: Jorge Di Paola, Augusto B. Federici, P.M. Mannucci, Maria T. Canciani, Marcie Kritzik, Thomas J. Kunicki, Diane Nugent
Journal: Blood (1999)
Potable Water as a Cause of Sporadic Cases of Community-Acquired Legionnaires' Disease
Authors: Janet E. Stout, Victor L. Yu, Paul Muraca, Jean Joly, Nancy Troup, Lucy S. Tompkins
Journal: New England Journal of Medicine (1992)

The environmental sources of sporadic, community-acquired legionnaires' disease are largely unknown, and culturing of water sources after identification of a case is currently not recommended. We conducted a prospective study of sporadic cases of community-acquired legionnaires' disease to determine whether the environmental reservoirs could be identified.We cultured samples of potable water obtained from sources to which each of 20 patients with culture-confirmed, community-acquired legionnaires' disease had been exposed during the two weeks before the onset of symptoms. Monoclonal-antibody subtyping and restriction-endonuclease analysis were performed on the legionella isolates recovered from both the patients and the associated environmental cultures.For 8 of the 20 patients, isolates of Legionella pneumophila with identical subtypes were identified in cultures from both the patient and the potable water to which the patient had been exposed. The environmental reservoirs linked to the infections were the water supplies of two private residences, two nursing homes, two hospital outpatient clinics, and an industrial plant.Potable-water supplies that harbor L. pneumophila are an important source of community-acquired legionnaires' disease. Future studies should include attempts to identify the environmental sources of this infection.
SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study
Authors: Muhammad Abdul-Ghani, Stefano Del Prato, Robert Chilton, Ralph A. DeFronzo
Journal: Diabetes Care (2016)

Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk. Thus, novel strategies to reduce CVD risk in T2DM patients are needed. The recently published BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study demonstrated that in T2DM patients with high CVD risk empagliflozin reduced the primary major adverse cardiac event end point (CV death, nonfatal myocardial infarction, nonfatal stroke) by 14%. This beneficial effect was driven by a 38% reduction in CV mortality with no significant decrease in nonfatal myocardial infarction or stroke. Empagliflozin also caused a 35% reduction in hospitalization for heart failure without affecting hospitalization for unstable angina. Although sodium-glucose cotransporter 2 inhibitors exert multiple metabolic benefits (decreases in HbA1c, body weight, and blood pressure and an increase in HDL cholesterol), all of which could reduce CVD risk, it is unlikely that the reduction in CV mortality can be explained by empagliflozin's metabolic effects. More likely, hemodynamic effects, specifically reduced blood pressure and decreased extracellular volume, are responsible for the reduction in CV mortality and heart failure hospitalization. In this Perspective, we will discuss possible mechanisms for these beneficial effects of empagliflozin and their implications for the care of T2DM patients.