tbuckley/cabot-search huggingface dataset:
Changes in Lymphoreticular Tissues During Growth of a Murine Adenocarcinoma. III. Plaque-Forming Cell Response in Lymph Nodes and Spleen&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G. F. Rowland, A. J. Edwards, C. M. Hurd, M. R. Sumner
Journal: JNCI Journal of the National Cancer Institute (1971)

Changes in immune responsiveness in the lymph nodes and spleen throughout the lifespan (about 30 days) of mice bearing syngeneic mammary tumors were followed with the use of the plaque-forming cell (PFC) response to sheep red blood cells (SRBC). After an initial rise, the total number of competent cells in the lymph nodes fell 15 days after tumor implantation and was reduced by 38% in the terminal stages of malignancy. Changes in the spleen were more marked and also showed a fall in the ratio of competent to noncompetent cells—this appearing to be an immunosuppressive effect of the tumor. PFC/million spleen cells fell after 15 days and in the last week were reduced by over 90%. The total number of PFC/spleen increased 100% by 17 days and then decreased sharply to 70% below control levels during the last week. Transfer of spleen cells from the tumor-bearing mice to irradiated syngeneic animals revealed a large increase in the number of PFC's. Thus, in this experimental system, the number of potentially immunocompetent cells greatly increases during tumor growth, but in advanced malignancy these cells are prevented from responding to SRBC unless they are removed from the inhibitory environment of the tumor-bearing animal.
Application of an Indirect Paired Radioiodine-Labeled Antibody Technique to Adenovirus-12 Tumor Serology&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: James R. McCammon, David S. Yohn
Journal: JNCI Journal of the National Cancer Institute (1971)

The indirect paired radioiodine-labeled antibody technique was developed to detect antibodies to adenovirus-12-induced tumor antigen(s). This technique was more sensitive than indirect immunofluorescence and markedly more sensitive than complement fixation. It provides a means to rapidly screen large numbers of sera for antibodies to various virus-induced antigens.
Basic Issues in Population Screening for Cancer&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: P Cole, A S Morrison
Journal: JNCI Journal of the National Cancer Institute (1980)

The value of population screening as an approach to cancer control is controversial because the objectives, benefits, costs, and potential adverse effects of screening programs are not widely agreed upon, nor are the many difficulties involved in evaluating a cancer screening program well recognized. A review of the issues pertinent to cancer screening and their interrelationships is presented. The characteristics of a particular cancer that should be considered before it becomes the target of a screening program are described; emphasis is placed on the prevalence of the detectable preclinical phase. The features of a good screening test are reviewed and the importance of specificity is indicated. Methods for evaluation of screening programs are considered, and the need for measurement of the effects of screening on the mortality rate is emphasized. The biases inherent in some commonly used evaluation procedures, especially lead time bias and length bias, are discussed. The possible adverse effects of cancer screening are pointed out, especially its capacity to increase morbidity. Several approaches to improving cancer screening programs are presented. Finally, the relevance of knowledge regarding the optimum interscreening interval to cancer control and to research issues is described.
Multistage Models and Primary Prevention of Cancer
Authors: Nicholas E. Day, Charles C. Brown
Journal: JNCI Journal of the National Cancer Institute (1980)

Removal of carcinogenic exposures should reduce the subsequent risk for developing cancer. Of interest are the extent of the reduction and the speed with which it takes place. Multistage models with more than two stages for tumor development predict different patterns of chaniging risk following removal of a carcinogenic exposure, depending upon the stage in the process that the carcinogen predominantly affects. The fall in risk following removal of a early-stage carcinogen is only slowly evident, whereas removal of a late-stage carcinogen leads to a more rapid reduction in excess risk. Experimental and epidemiologic data are reviewed, and both early- and late-stage effects are seen. The long-term danger arising from entry into the environment of early-stage carcinogens is discussed, and it is shown that by the time human evidence that a hazard does exist becomes available, those already exposed may well have accumulated their fully effective doses.
Survival and Functional Stability in Chronic Kidney Disease Due to Surgical Removal of Nephrons: Importance of the New Baseline Glomerular Filtration Rate
Authors: Brian R. Lane, Sevag Demirjian, Ithaar H. Derweesh, Toshio Takagi, Zhiling Zhang, Lily Velet, Cesar E. Ercole, Amr F. Fergany, Steven C. Campbell
Journal: European Urology (2015)
COPD Comorbidity Network: Connecting the dots
Authors: Miguel Divo, Victor Pinto-Plata, Carlos Cabrera Lopez, Ciro Casanova, Jorge Zagaceta, Juan Pablo De Torres, Jose Maria Marin, Javier Zulueta, Pablo Sanchez Salcedo, Claudia Cote, Bartolome Celli
Journal: European Respiratory Journal (2013)

Comorbidities are frequent in COPD and a known subset of them influences mortality. However, the relations between them are poorly understood. In this study, we describe the COPD comorbidity network in the BODE cohort by exploring co-occurrence clusters using system network graphic analysis.  Methods: We included 1659 COPD subjects and comorbidities were recorded systematically. Spearman’s coefficient were calculated between comorbidities, and those with significant correlation (p  Results: The network is composed of 79 comorbidities with prevalence ranging from 0.5 to 52% and 568 edges. We found a quadratic relation between prevalence and degree of connection = 7.5 + 160.3*prev - 324.0*(prev-0.06)^2, R2=0.75 (p  Conclusion: Certain COPD comorbidities are interconnected and the degree of connection follow a quadratic pattern with their prevalence. In this complex network, particular motifs were identified perhaps amenable to specific interventions.
The novel elastase inhibitor BAY 85-8501: Bioavailability and Food effect study to evaluate pharmacokinetics of tablet formulations
Authors: Johannes Nagelschmitz, Michael Becka, Dorina Kaufel, Stephan Schwers, Georg Wensing
Journal: European Respiratory Journal (2014)

Human neutrophil elastase (HNE) is a key mediator of tissue remodeling and inflammation. An excess of HNE activity has been implicated in the pathogenesis of inflammatory pulmonary diseases, e.g. bronchiectasis, COPD and pulmonary hypertension. HNE inhibitors could potentially restore the protease/anti-protease balance in these diseases providing a new therapeutic option.  BAY 85-8501 is a novel, selective and reversible HNE inhibitor with activity in the picomolar concentration range, which reveals target inhibition in the lung and ameliorates pulmonary inflammation in preclinical models.  Relative bioavailability of 0.1 and 0.5 mg BAY 85-8501 immediate release tablets (tbl) and influence of concomitant food intake on 0.5 mg tbl was investigated in a 4-fold crossover study in 12 healthy male subjects. Treatments were single doses of tbl 0.1 and 0.5 and oral liquid 0.5 mg fasted and tbl 0.5 mg with food.  All treatments were safe and well tolerated, no changes of clinical safety (BP, HR, ECG) and clinical laboratory parameters occurred.  Tablet formulations of 0.5 and 0.1 mg revealed a comparable dose-normalized exposure, however, absorption rate was nearly halved for the tablet. Intake of American breakfast reduced the absorption rate (max. concentration (40 %) reached after 4 h), but not its extent. Terminal half-life after 0.5 mg ranged from 110 to 121 h.  Bioavailability in terms of AUC was comparable between solution and tablet. Food intake decreased absorption rate, but not absorption extent. Tablets have favorable PK and are safe for further treatment in clinical studies.
Cardiovascular, metabolic prognosis and mortality of the positional sleep apnea syndrome: An historical cohort study including 240 patients
Authors: Vanessa Bironneau, Elise Antone, Pierre Ingrand, Joel Paquereau, Jean Claude Meurice
Journal: European Respiratory Journal (2013)

Introduction: Positional sleep apnea syndrome (PSAS) is poorly defined and rarely taken into account, whose complications have not been previously explored.  Aim of the study: To evaluate the evolution of cardiovascular and metabolic complications, and mortality in PSAS patients, depending on the severity of the overall and supine apnea hypopnea index (IAH). The influence of continuous positive airway pressure (CPAP) was evaluated.  Methods: A cohort study has been performed over a period of 75.9 ± 8 months on 240 patients who benefited from an initial polysomnographic recording. They were divided into 3 groups: Normal-normal (NN; n=76) (AHI   10/h, non supine AHI   10/h, supine AHI> 10/h, non supine AHI   Results: Cardiovascular comorbidity, mainly represented by hypertension, was significantly higher in patients with PP AHI> 30 (p   Conclusion: PSAS is associated with an increased metabolic and cardiovascular comorbidity, and must be taken into account, even when the overall AHI is considered within normal range.
Genetic analysis of neurodegeneration.. the end game
Authors: John Hardy
Journal: Molecular Neurodegeneration (2013)

In my talk I will discuss how genetic analysis now allows us to dissect both causative and predisposing genes for neurodegenerative diseases. Mendelian diseases can be found by positional cloning and sequencing... rare, high risk variants can be found by exome sequencing and burden analysis and common low risk variants can be found by genome wide association analyses. I will show how, when loci for disease are found, they map functionally into specific biochemical pathway. This property is also helpful in identifying new loci for which the statistical evidence is less than convincing. With regard to Alzheimer’s disease, the well known mendelian genes are APP and PSEN1 and PSEN2. In addition to apoe, genome wide association studies have identified now nearly 20 loci which map onto four pathways, cholesterol metabolism, the innate immune system, endosomal vesicle recycling and protein ubiquitination. At the time of writing this abstract, TREM2, which is involved in the innate immune system and control of miscroglial activation is the only declared rare variant of high effect (o.r. ~5), but several other genes have data in the publication process. I will discuss these issues and update on the current state of play for Alzheimer genetics and describe how we can move towards the completion of genetic analysis.
Two-Stage Model for Carcinogenesis: Epidemiology of Breast Cancer in Females&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S H Moolgavkar, N E Day, R G Stevens
Journal: JNCI Journal of the National Cancer Institute (1980)

A biologically based two-stage model for carcinogenesis is presented that relates events occurring at the cellular level to epidemiologic features of breast cancer in females. This model, which accommodates the physiologic responses of breast tissue to menarche, menopause, and pregnancy, predicts age-specific incidence curves that are in close quantitative agreement with those observed in six test populations: Connecticut, Denmark, Finland, Slovenia, Iceland, and Osaka, Japan. According to the model, hormones influence the epidemiology of breast cancer in females by their action on the kinetics of growth of nonneoplastic breast tissue. As a consequence, it is argued that hormones are likely to be unimportant in determining overall risk in populations. The protective effect of an early first birth predicted by the model is in good quantitative agreement with data from a multinational study. Other epidemiologic features of breast cancer are logically explained within the framework of the model. No feature of the epidemiology of breast cancer requires that premenopausal and postmenopausal breast cancer be considered distinct entities from the point of view of pathogenesis.
The curious case of women in hospital medicine
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2015)

What is the status of women in medicine? Women are in the majority in medical schools and soon in the workforce. Women serve as chief medical officers, presidents of royal colleges and editors of major international journals. Admittedly, a female doctor is yet to host Top Gear but every meaningful glass ceiling is being smashed through.

Still, something does not feel right? The ‘feminisation’ of medicine seems patchy at best. The pain is greatest in hospital specialties that offer little scope for a career break to bring up children. Evidence already points to gender differences in doctors’ working hours, specialty choices and communication styles, but why these differences exist is less well studied. A qualitative study design, as employed by Laura Jefferson and colleagues, can help explore the reasons for gender variations.1

The researchers find that where male consultants demonstrate direct, abrupt and didactic communication styles, female consultants are more accepting of problems and more affable. A consultation with a female consultant is more psychosocial and holistic in nature. Struggling with workload and craving greater work–life balance manifests more stress in women, who perceive barriers to progress in their careers. On a more positive note, colleagues and patients seem to find female consultants more approachable.

Perhaps the sexes can be united by embracing curiosity? Ami Schattner, in an editorial, describes curiosity as a ‘universal and omnipotent, predominantly human trait’ that should be prominent in medical education, training and clinical practice.2 Cat owners may wish to dispute which species is best possessed with curiosity but medical students and doctors might indulge this instinct more for the betterment of patient care.

Preferably, curiosity rather than commerce is the primary driver behind medical research, and presumably motivated the pioneers of cluster randomised trials, whose role is explained in a brief history of this interesting research methodology.3
A randomised controlled trial investigating the effects of varenicline on sympathovagal balance during acute nicotine withdrawal
Authors: Helge Haarmann, Alexandra Gossler, Slavtcho Bonev, Stefan Andreas, Tobias Raupach
Journal: European Respiratory Journal (2014)

Background  Habitual smoking might elicit a sustained shift in autonomic balance. As a consequence, acute withdrawal might be associated with reverse changes in sympathovagal balance. We hypothesised that these changes are amenable to pharmacological interventions.  Methods  In this randomised controlled trial, smokers (n=36) willing to quit were examined using microneurographic recordings of muscle sympathetic nerve activity (MSNA), baroreflex sensitivity (BRS) and heart rate variability (HRV) before a quit attempt and during acute withdrawal (i.e. three days into their quit attempt). In addition, moderating effects of varenicline and placebo were assessed in a randomised controlled trial.  Results  For the primary endpoint, changes in MSNA (bursts/100 heart beats) between baseline and withdrawal did not differ significantly between the varenicline and placebo group (-5.29 ± 13.9 vs. -3.02 ± 10.03; p=0.697). Smokers using placebo showed no significant change in MSNA (bursts/100 heart beats) during acute withdrawal as compared to continuing smokers (-3.02 ± 10.03 vs. +0.64 ± 12.62; p=0.516). Results pointed towards a decreased BRS (change by -1.43 ± 6.12 vs. +5.01 ± 7.84 ms/mmHg; p=0.104) during acute withdrawal in the varenicline group as compared to placebo. No relevant differences in HRV were observed between groups.  Conclusion  Compared with placebo, varenicline did not have significant adverse effects on the autonomic nervous system. This corroborates clinical data suggesting the cardiovascular safety of varenicline.  This study was supported by an investigator-initiated grant from Pfizer.
Brief Report: Autologous Stem Cell Transplantation Restores Immune Tolerance in Experimental Arthritis by Renewal and Modulation of the Teff Cell Compartment
Authors: Eveline M. Delemarre, Sarah T. A. Roord, Theo van den Broek, Evelien Zonneveld‐Huijssoon, Wilco de Jager, Henk Rozemuller, Anton C. Martens, Femke Broere, Nico M. Wulffraat, Tibor T. Glant, Berent J. Prakken, Femke van Wijk
Journal: Arthritis & Rheumatology (2013)

Objective Autologous stem cell transplantation (ASCT) induces long‐term drug‐free disease remission in patients with juvenile idiopathic arthritis. This study was undertaken to further unravel the immunologic mechanisms underlying ASCT by using a mouse model of proteoglycan‐induced arthritis (PGIA). Methods For initiation of PGIA, BALB/c mice received 2 intraperitoneal injections of human PG in a synthetic adjuvant on days 0 and 21. Five weeks after the first immunization, the mice were exposed to total body irradiation (7.5 Gy) and received (un)manipulated bone marrow (BM) grafts from mice with PGIA. Clinical scores, T cell reconstitution, (antigen‐specific) T cell cytokine production, and intracellular cytokine expression were determined following autologous BM transplantation (ABMT). Results ABMT resulted in amelioration and stabilization of arthritis scores. BM grafts containing T cells and T cell–depleted grafts provided the same clinical benefit, with similar reductions in PG‐induced T cell proliferation and the number of PG‐specific autoantibodies. In vivo reexposure to PG did not exacerbate disease. Following ABMT, basal levels of disease‐associated proinflammatory cytokines (interferon‐γ [IFNγ], interleukin‐17 [IL‐17], and tumor necrosis factor α [TNFα]) were reduced. In addition, restimulation of T cells with PG induced a strong reduction in disease‐associated proinflammatory cytokine production. Finally, although the remaining host T cells displayed a proinflammatory phenotype following ABMT, IFNγ, IL‐17, and TNFα production by the newly reconstituted donor‐derived T cells was significantly lower. Conclusion Taken together, our data suggest that ABMT restores immune tolerance by renewal and modulation of the Teff cell compartment, leading to a strong reduction in proinflammatory (self antigen–specific) T cell cytokine production.
Investigation of reactions to dental materials
Authors: D.J. Gawkrodger
Journal: British Journal of Dermatology (2005)

Patients undergoing dental treatment can be exposed to a wide range of potential allergens, but adverse events seem infrequent. Patients with symptoms or signs of stomatitis, burning, tingling, cheilitis, oral lichenoid lesions, lip and facial swelling may relate their problems to dental treatment or to the use of dental products. Investigation for immediate type or delayed type hypersensitivity is indicated using patch testing, prick testing and blood tests for allergen-specific IgE. The main allergic reactions found in patients include contact allergy to metals, cosmetics, food additives, flavours and acrylates, and immediate type allergy to latex. Adverse reactions following the administration of local anaesthetics are seen in about 0.5% of cases, but immediate type allergy to these agents is rare. In dental staff, occupationally related problems are common and usually take the form of hand or facial dermatitis or respiratory disease. The most common allergic reactions in dental staff are immediate type allergy to latex, and contact allergy to rubber additives, fragrances, acrylates and formaldehyde. Occupational irritant problems causing hand dermatitis are probably more common in dental personnel than is dermatitis caused by contact allergy. Patch testing and tests for immediate type allergy are useful investigative methods in the investigation of patients who present with oral or facial symptoms possibly related to dental treatments and are also beneficial in dental personnel who present with hand or facial dermatitis or respiratory symptoms.
Quality of life in relation to the traffic indicators NO2 and NOx: Results from the Swedish GA2LEN survey
Authors: Bertil Forsberg, Johan Nilsson Sommar, Alexandra Ek, Sven-Erik Dahlen, Roelinde Middelveld, Anders Bjerg Bäcklund, Helen Bertilsson, Linda Ekerljung, Andrei Malinovschi, Christer Janson
Journal: European Respiratory Journal (2013)

Background  Worsening of asthma has been found associated with traffic pollution indicators.  Aims  The aim of the study was to evaluate the impact of traffic pollution on quality of life in asthmatic subjects, individuals with CRS, and controls.  Methods  Within the Swedish GA2LEN Study, 605 asthmatics with and without CRS, 110 individuals with CRS only and 226 controls were surveyed. The mini Asthma Quality of life Questionnaire (mAQLQ), the Euro Quality of Life (EQ-5D) health questionnaire, spirometry, skin prick test, exhaled nitric oxide, smell test and peak nasal inspiratory flow were used. Air pollution levels at the home address were modeled using dispersion models.  Results  Levels of NO2 (mean 10 microg/m3) and NOx (14 microg/m3, IQR 8.7-70) were similar among groups (controls, asthmatics, individuals with CRS, and asthmatics with CRS). The mAQLQ overall score was not found associated with NO2 or NOx, with or without adjustments, and neither was scores within each of the four domains of mAQLQ: symptoms, activity limitations, emotional functions, and effects of environmental stimuli. The mean EQ-5D index value, based on the five dimensions mobility, self-care, usual activities, pain/discomfort and anxiety depression, was also found unrelated to NO2 and NOx. Stratification by condition did not reveal any differences in NO2 or NOx related effects.  Conclusions  Within these exposure levels, NO2 and NOx appear not to affect quality of life among controls, asthmatics, individuals with CRS, or asthmatics with CRS. This could perhaps be explained by selection bias related to susceptibility (avoidance), moderate exposure levels or confounders related to the type of residential area.
Cigarette Smoking Increases White Blood Cell Aggregation in Whole Blood
Authors: A B Bridges, A Hill, J J F Belch
Journal: Journal of the Royal Society of Medicine (1993)

We studied the effect of chronic cigarette smoking on white blood cell aggregation, increased aggregation predisposes to microvascular occlusion and damage. Current smokers had significantly increased white blood cell aggregation when compared with non smokers. The presence of chronically activated white blood cells in current smokers may be relevant in the pathogenesis of ischaemic vascular disease.