tbuckley/cabot-search huggingface dataset:
A Multicenter Randomized Trial of Ibandronate Compared With Single-Dose Radiotherapy for Localized Metastatic Bone Pain in Prostate Cancer
Authors: Peter Hoskin, Santhanam Sundar, Krystyna Reczko, Sharon Forsyth, Natasha Mithal, Bruce Sizer, David Bloomfield, Sunil Upadhyay, Paula Wilson, Amy Kirkwood, Michael Stratford, Mark Jitlal, Allan Hackshaw
Journal: JNCI Journal of the National Cancer Institute (2015)

The radiotherapy or ibandronate (RIB) trial was a randomized multicenter nonblind two-arm trial to compare intravenous ibandronate given as a single infusion with single-dose radiotherapy for metastatic bone pain. Four hundred seventy prostate cancer patients with metastatic bone pain who were suitable for local radiotherapy were randomly assigned to radiotherapy (single dose, 8 Gy) or intravenous infusion of ibandronate (6mg) in a noninferiority trial. Pain was measured using the Brief Pain Inventory at baseline and four, eight, 12, 26, and 52 weeks. Pain response was assessed using World Health Organization (WHO) criteria and the Effective Analgesic Score (EAS); the maximum allowable difference was ±15%. Patients failing to respond at four weeks were offered retreatment with the alternative treatment. Quality of life (QoL) was assessed at baseline and four and 12 weeks. Because the trial was designed with a 5% one-sided test, we provide 90% confidence intervals (two-sided) for differences in pain response. Overall, pain response was not statistically different at four or 12 weeks (WHO: −3.7%, 90% confidence interval [CI] = −12.4% to 5.0%; and 6.7%, 90% CI = −2.6 to 16.0%, respectively). Corresponding differences using the EAS were −7.5% and −3.5%. However, a more rapid initial response with radiotherapy was observed. There was no overall difference in toxicity, although each treatment had different side effects. QoL was similar at four and 12 weeks. Overall survival was similar between the two groups but was better among patients having retreatment than those who did not. A single infusion of ibandronate had outcomes similar to a single dose of radiotherapy for metastatic prostate bone pain. Ibandronate could be considered when radiotherapy is not available.
Physical inactivity and obesity is not a myth: Dr Steven Blair comments on Dr Aseem Malhotra's editorial
Authors: Steven N Blair
Journal: British Journal of Sports Medicine (2015)

Malhotra et al 1 claim that ‘physical activity does not promote weight loss’. I respectfully disagree with many of the claims in the report.

1.  The authors claim that physical activity does not promote weight loss. Similar points were made in an article by Luke and Cooper published in 2013,2 and my colleagues and I published a commentary showing the weaknesses of their interpretation of the data.3 If you are interested in the details, please review that commentary. More detailed information on many of these points is presented in a position statement from the American College of Sports Medicine.4 

2.  A second flawed point is the claim that over the past 30 years, there has been little change in physical activity, so the obesity epidemic must be due to increases in caloric intake. If one considers self-reported …
Transgenic tubular cell expression of class II is insufficient to initiate immune renal injury.
Authors: A M Jevnikar, G G Singer, T Coffman, L H Glimcher, V E Kelley
Journal: Journal of the American Society of Nephrology (1993)

Autoimmune disease in mouse models of lupus nephritis is associated with enhanced renal tubular epithelial cell (TEC) expression of major histocompatibility complex (MHC) class II (Ia) molecules. It is unknown whether de novo TEC expression of syngeneic la alone can initiate immune attack or whether expression is secondary to cytokines released by infiltrating lymphocytes. To establish if the expression of high levels of self-MHC molecules alone can initiate immune renal injury in the adult animal, kidneys from transgenic C57BL/6 (B6) mice (Ins-I-E) bearing constitutively high levels of I-Eb on proximal TEC were transplanted into nephrectomized male B6 x C3H F1 hybrid mice (I-Eb/k). Control mice received kidneys from I-Eb negative, nontransgenic B6 mice, and all transplant recipient mice were evaluated for renal disease. At the end of the study (> 8.3 months mean survival), the transgenic transplant recipients did not become proteinuric (< 1+ urinary protein) and had normal serum creatinine levels (control = 95 +/- 8 versus transgenic transplants = 116 +/- 23 mumol/L; N = four/group), and the kidneys remained histologically normal. These results establish that the expression of high levels of transgenic MHC class II molecules on TEC is insufficient to initiate autoimmune injury in this model. It is suggested that, in addition to MHC class II molecules, other signals or accessory molecules are required from TEC to initiate immune renal injury.
Former Cancer Patients as Counselors of Newly Diagnosed Cancer Patients&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: P S Houts, C W Whitney, R Mortel, M J Bartholomew
Journal: JNCI Journal of the National Cancer Institute (1986)

This study tested the hypothesis that counseling of newly diagnosed cancer patients by former cancer patients will increase the use of coping strategies and reduce psychological stress beyond what can be accomplished by just counseling from professional staff. Thirty-two newly diagnosed patients in a gynecologic oncology service were subjects in this study. All subjects received supportive services from professionals assigned to the service. Control group patients received just the professional support program, while the experimental group patients received professional support plus additional counseling by former cancer patients that emphasized four coping strategies characteristic of patients who have adapted well to cancer. Results 6 and 12 weeks after entering the study showed no statistically significant differences in emotional status between experimental and control groups and only one significant difference in coping behaviors that was opposite to what was predicted. The findings do not support the hypothesis.
Chronic obstructive pulmonary disease at the cleanup workers at Chernobyl accident per clinical and instrumental indicators at the remote period after low-dose radiation exposure
Authors: Kostiantyn Bazyka, Victor Sushko, Lyudmila Shvayko
Journal: European Respiratory Journal (2011)

The aim of this study was to define the clinic and the pulmonary function (PFT) in patients with COPD at the remote period after low-dose ionizing radiation exposure and inhalation of radionuclides emergency descent.

Methods: Group1-57 COPD cleanup workers (individual documented dose of irradiation: 0,01 to 0,5 sZv) exposed to external and internal irradiation (mean age 62,1±1,4 yrs), group2 - 20 COPD patients who were not exposed to radiation (mean age 63,2±2,9 yrs). Clinical examination included-questioning, physical examination, MRC scale, BODE index. PFT was measured using spirometry, bodypletismography and DLCO.

Results: It was found out the significant reduction of lung capacity, a clear violation of the ratio of lung volume, due to certain growth of residual volume and total lung capacity, and reduction of diffuse capasity in a group of clean-up workers COPD patients in compareson with nosological control.Complaints of breathlessness varying degrees of intensity significantly more often expressed by patients with COPD who suffered from Chernobyl compared with control group.

Conclusion: Analysis pathognomonic symptoms for bronchopulmonary disease showed the presence of cough, sputum selection, shortness of breath, in most patients, but complaints of breathlessness varying degrees of intensity significantly more often expressed by patients with COPD who suffered from Chernobyl compared with control group, indicating worse quality of life. Also we indicate the presence of distinct pulmonary hyperinflation, emphysema, and diffuse lung function in a group 1 compared with control.
Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2
Authors: Syed Sohail Ahmed, Wayne Volkmuth, José Duca, Lorenzo Corti, Michele Pallaoro, Alfredo Pezzicoli, Anette Karle, Fabio Rigat, Rino Rappuoli, Vas Narasimhan, Ilkka Julkunen, Arja Vuorela, Outi Vaarala, Hanna Nohynek, Franco Laghi Pasini, Emanuele Montomoli, Claudia Trombetta, Christopher M. Adams, Jonathan Rothbard, Lawrence Steinman
Journal: Science Translational Medicine (2015)

Similarity between influenza nucleoprotein and hypocretin receptor 2 may trigger vaccine-associated narcolepsy.
Serine-Glycine Requirement of Phytohemagglutinin-Stimulated Lymphocytes2
Authors: Robert Dubrow, Lewis I. Pizer, Jerome I. Brody
Journal: JNCI Journal of the National Cancer Institute (1973)

Phytohemagglutinin-stimulated human peripheral blood lymphocytes grown in vitro have a requirement for serine and glycine. Glycine partially relieves the requirement and serine totally relieves it. The extent of the requirement depends on the cell density of the culture. Phytohemagglutinin-stimulated lymphocytes utilize much greater amounts of serine for macromolecular synthesis than do unstimulated lymphocytes. This system can be used for testing chemotherapeutic agents which selectively inhibit the growth of leukemic cells by restricting the supply of serineavailable to them.
Mammary Tumor Virus Particles in the Submaxillary Gland, Seminal Vesicle, and Nonmammary Tumors of Wild Mice2
Authors: Robert W. Rongey, Alena H. Abtin, John D. Estes, Murray B. Gardner
Journal: JNCI Journal of the National Cancer Institute (1975)

Type - B mammary tumor virus particles were detected by electron microscopy in the submaxillary glands ot 6 of 27 freshly trapped, pregnant wild mice (Mus musculus). Type - B particles were also detected in 3 of 24 seminal vesicles and 2 pulmonary adenomas from wild mice. Intracytoplasmic Type - A virus particles were found in 7 spontaneous non mammary tumors (lymphoma, hepatoma, lung adenoma) of aging wild mice. Type - C virus particles were also detected in many of these tissues.
First to seventh diseases: discarded diagnoses?
Authors: Mitesh Patel, Rodger Charlton
Journal: BMJ (2015)

A mother brought in her 5 year old child with a rash, asking, “Doctor, is this fifth disease?” Good question, but could it be one of the other six, and why are these childhood exanthema diagnostic terms mostly not used, other than “fifth disease”?

Let’s start at the beginning. “First disease” (measles), first scientifically described around the 10th century, is caused by measles virus. A maculopapular rash initially presents on the face and behind the ears. Bluish white Koplik’s spots may be …
Effect of roflumilast on morphological changes in mucous membrane of bronchi in patients with severe chronic obstructive pulmonary disease
Authors: Mykola Ostrovskyy, Iryna Savelikhina, Oleksandr Varunkiv, Mariana Kulynych-Miskiv
Journal: European Respiratory Journal (2014)

Background. COPD is now recognised to be a condition of global importance because of high morbidity and risk of premature death of millions of people. There were performed biopsies of the mucous membrane of the bronchi in 9 people with severe COPD before treatment and after 30 and 180 days treatment with roflumilast . The material of the research was bronchoalveolar lavage and bronchial biopsy materials received on the level of proximal bronchi bifurcation to segmental bronchi during fiberoptic bronchoscopy.

Results of the study: At the and of 30-days treatment with roflumilast on the background of COPD maintance therapy, we have identified better results in comparison with the results before treatment. The main signs of improvement in the morpho-functional state of epithelial cells can be considered: moderate hypertrophy of the nucleus, cytoplasm vacuolization reduce, the number of myofibroblasts are reduced, some of them showed signs of degradation. A six-month therapy with the use of roflumilast gave its positive results. In the pathohistological picture of a bronchus mucous membrane there were outlined positive changes in the epithelial tissue as well as in the connective tissue of lamina propria of mucous membrane.

Conclusions: After a 180-day treatment with roflumilast on the background of a basic therapy of patients with COPD III there was detected the most positive dymanics of pathohistological picture of a bronchus mucous membrane in the epithelial tissue as well as in the connective tissue of lamina propria of mucous membrane, in comparison with a 30-day treatment.
Case control study to assess the prevalence of obstructive airway disease in flour mill workers
Authors: Madhura Fadnis, Sharad Agarkhedkar, Tushar Sahasrabudhe
Journal: European Respiratory Journal (2012)

In India, the grain flour required for household cooking is made by grinding grains in machine operated flour mills, which are usually small sized unventilated rooms. These machines are operated by a single unskilled worker who works in shift duties of 6 hours. During operation, the machine generates large amount of flour or grain dust and produces clouds of flour that surrounds the worker thus predisposing him to obstructive airway disease. 46 flour mills in the city were visited. Customers of the mills with short exposure to flour dust served as controls who were matched for age and sex. Those with active lung infection or scarring and tobacco smokers were excluded from both groups. On site measurement of PEFR was done, using Mini Wright's peak flow meter for a total of 44 workers and 44 controls. The intention of using a peak flow meter instead of spirometry was to evaluate usefulness of this simple modality which can be easily applied in villages where flour mills are more common and spirometry is not available. The peak flow readings between >100%, 80-99%, 50-79% and <50% predicted value were labelled as normal, green, yellow and red zone respectively. 22/44 workers had normal PEFR as against 38/44 controls. 19 and 3 workers were in green and yellow zone respectively whereas 6/44 controls were in green zone.19/27 workers using a face mask had normal PEFR as against only 3/17 not using the mask (P<0.0001). Only 1/46 mills had enclosed machine with dust filter and the worker was in green zone even after 15 years of work duration. The study indicates a potential occupational hazard to the flour mill workers. Use of face mask or enclosure of machine can potentially reduce the risk.
Can roxithromycin improve quality of life in bronchiectatic patients
Authors: Pimchanok Asintam, Nantaka Kiranantawat, Siwasak Juthong
Journal: European Respiratory Journal (2012)

Rationale: Patients with bronchiectasis suffer from sputum production and exacerbated. The aims of this study were roxithromycin, an anti-inflammatory macrolide antibiotic, could alter clinical outcome. Material and Methods: A randomized, double blinded, placebo controlled study was conducted to evaluate the effect of a 12-weeks of roxithromycin (300 mg/d) and a 12-week wash out period in HRCT proved bronchiectasis.  Results: 30 bronchiectasis patients mainly from postuberculosis with history of 2.5 times exacerbation per year were studies. During the treatment period patients in the roxithromycin group (n=15, mean age 67 yrs) and the placebo group (n=15, mean age 65 yrs) had improved quality of life by total SGRQ scores 7.31 ± 17.14 vs. 6.31 ± 18.11(mean different +/-SD) but could not reach statistical significant (p = 0.53), at follow up wash out period there was more improvement in all domains of SGRQ scores in the roxithromycin group than the placebo group especially in the impact domain 4.17 vs -3.24 (mean different). There was no parallel improvement in sputum volume, symptom scores and pulmonary function tests. Two patients in treatment group and a patient in control group developed exacerbation and no patients in either group reported side effects. The microbiology results showed colonization of P. aeruginosa and K. pneumonia without any reported emerging drug resistance.  Conclusion: 12-week roxithromycin 300 mg once daily in symptomatic stable bronchiectatic patients did not show significant improvement of QoL by SGRQ scores, reduced sputum volume nor improved lung function. Further long term study of anti-inflammatory macrolide should be done in symptomatic bronchiectatic patient.
MECHANISMS OF LYSOSOMAL ENZYME RELEASE FROM LEUKOCYTES EXPOSED TO IMMUNE COMPLEXES AND OTHER PARTICLES
Authors: Gerald Weissmann, Robert B. Zurier, Paul J. Spieler, Ira M. Goldstein
Journal: The Journal of Experimental Medicine (1971)

Human PMN release lysosomal enzymes (ß-glucuronidase, acid phosphatase) when exposed to immune complexes, but do not release cytoplasmic LDH. The cells remain viable, and failure of LDH to appear in supernatants is not due to selective absorption or inactivation. Release of enzymes is not due to platelet contamination and is only partially enhanced by fresh serum. The selective release of lysosomal enzymes after uptake of complexes resembles that induced by inert particles of zymosan, and can be distinguished from the concurrent release of all enzymes after cell death induced by membrane-lytic crystals of MSU. Uptake of complexes, zymosan, or MSU particles is accompanied by concomitant increases in C-1 oxidation of glucose. Although MSU-induced damage can be retarded by the presence of Tris buffer, immune complexes and zymosan selectively release lysosomal hydrolases in the presence or absence of Tris buffer. Agents which elevate the level, within cells, of cAMP (PGE1, theophylline, 2-CA) and cAMP itself inhibit the selective extrusion of acid hydrolases from leukocytes without affecting the viability of cells. Leukocytes may respond to immune particles by regurgitating a portion of their lysosomal hydrolases during phagocytosis.
Phase II study of goserelin for patients with postmenopausal metastatic breast cancer.
Authors: T Saphner, A B Troxel, D C Tormey, D Neuberg, N J Robert, K J Pandya, J H Edmonson, R J Rosenbluth, M D Abeloff
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine the response rate of postmenopausal breast cancer patients to the gonadotropin-releasing hormone (GN-RH) agonist, Zoladex (goserelin; ICI Pharma, Wilmington, DE). PATIENTS AND METHODS A multi-institutional single-agent trial in postmenopausal patients was conducted. Serum levels of follicle-stimulating hormone (FSH), testosterone, and estradiol were requested before and after Zoladex treatment. RESULTS For estrogen receptor-positive (ER+) patients, the response rate was 11%, with one complete response (CR) and three partial responses (PRs) among 36 eligible patients. Responses were of short duration. There were no responses among 16 estrogen receptor-negative (ER-) patients. CONCLUSION GN-RH agonists have activity in ER+ postmenopausal patients, but response rates are not as high as with other available endocrine therapies and the duration of response is short.
MMP7-degraded elastin is elevated in serum of patients with idiopathic pulmonary fibrosis
Authors: Jannie Marie Bülow Sand, Jacob Hull Kristensen, Bidisha Dasgupta, Mark Curran, Carrie Brodmerkel, Morten Asser Karsdal, Diana Julie Leeming
Journal: European Respiratory Journal (2014)

Introduction: Elastin is an abundant protein of the lung and is responsible for the elastic recoil following inflation. Idiopathic pulmonary fibrosis (IPF) causes altered elastin remodeling and fibrosis, which in part is believed to be mediated by MMP7, possibly resulting in the release of specific elastin fragments into the circulation.

Aims: Our aims were to investigate whether MMP7 generated specific elastin peptides; and to develop a highly specific assay for the assessment of MMP7-degraded elastin in serum, and investigate its ability to describe IPF.

Methods: A monoclonal antibody was raised against a MMP7 cleavage site in elastin and employed in an ELISA (ELM7). Technical robustness was tested and ELM7 levels were compared in intact elastin and elastin cleaved in vitro by MMP2, MMP7, MMP9, and neutrophil elastase (NE). ELM7 was assessed in baseline serum of 124 IPF patients from a prior phase 2 study (CTgov reg. [NCT00786201][1]) and in 19 healthy controls.

Results: Technical data for the ELM7 were acceptable. ELM7 exclusively recognized MMP7-cleaved elastin with concentrations elevated up to 17-fold above intact elastin and elastin cleaved by MMP2, MMP9, or NE, to which almost no reactivity was seen. Serum ELM7 was significantly elevated in IPF patients compared to controls (23%, p = 0.0353), but no correlation to FVC was observed.

Conclusion: MMP7 degradation of elastin resulted in unique protein fragments, which may be more disease specific than traditional elastin peptides. ELM7 was specific only towards MMP7-degraded elastin and was able to separate IPF patients from healthy controls. These preliminary results show a good potential for ELM7 as a marker of elastin remodeling during IPF.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00786201&atom=%2Ferj%2F44%2FSuppl_58%2FP823.atom
Early Stress and Later Response to Separation in Rhesus Monkeys
Authors: LAURENS D. YOUNG, STEPHEN S. SUOMI, HARRY F. HARLOW, WILLIAM T. MCKINNEY
Journal: American Journal of Psychiatry (1973)

The hypothesis that separation in early life predisposes one to later psychopathology was tested using two groups of rhesus monkeys of similar age. The experimental group had undergone the stress o...
Relationship Between Tumor Growth and Radiosensitivity
Authors: J.A. Belli, J.R. Andrews
Journal: JNCI Journal of the National Cancer Institute (1963)

To answer certain questions concerning the relationship between tumor growth and radiosensitivity, survival curves for a strain-specific murine leukemia (P-388) were determined with cells irradiated in vivo, in vitro, and “in situ” at various times following the transplantation of 106 cells per recipient. It was found that the D0 has a value of 110 r (Co60 γ-radiation) for the survival curve of cells of 1-day growth; this value increases to about 400 r for cells 4 and 7 days post transplantation. In addition, variation of the extrapolation number was observed, which generally was inversely related to the rise in D0 The finding of an extrapolation number for 3-day tumor cells of <1 (~0.6) suggested the presence of a population of cells of heterogeneous sensitivity. This heterogeneity was thought to be due to the presence of a few anoxic cells in a population otherwise fully oxygenated. The ratio of the reciprocal of the final slopes for the most resistant (7-day) to most sensitive (1-day) cells was 3.7. Tumor cells were also irradiated in vitro or in vivo in animals killed 15 minutes before exposure (referred to as irradiated in situ) at various times post transplantation. Radiosensitivity of cells irradiated in vitro or in situ appeared to be independent of growth stage. Survival-curve parameters in vitro were: n = 4.5, D0 = 151 r; in situ n = 7.2, D0 = 415 r. The ratio of the reciprocal of the final slopes (2.7) agrees with the oxygen-enhancement ratios reported for other mammalian cell strains.
Ebola Virus Disease: Experience and Decision Making for the First Patients outside of Africa
Authors: David S. Stephens, Bruce S. Ribner, Bryce D. Gartland, Nancye R. Feistritzer, Monica M. Farley, Christian P. Larsen, John T. Fox
Journal: PLoS Medicine (2015)

David Stephens and colleagues describe their experience of treating patients with Ebola virus disease at Emory University in the United States.