tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema
Authors: Els Wauters, Dominiek Smeets, Johan Coolen, Johny Verschakelen, Paul De Leyn, Marc Decramer, Johan Vansteenkiste, Wim Janssens, Diether Lambrechts
Journal: European Respiratory Journal (2011)

Clinical studies suggest that bronchial obstruction and emphysema increase susceptibility to lung cancer. We assess the possibility of a common genetic origin and investigate whether the lung cancer susceptibility locus on chromosome 5p15.33 increases the risk for bronchial obstruction and emphysema.  Three variants in the 5p15.33 locus encompassing the TERT and CLPTM1L genes were genotyped in 777 heavy smokers and 212 lung cancer patients. Participants underwent pulmonary function tests and computed tomography (CT) of the chest, and took questionnaires assessing smoking behaviour.  The rs31489 C-allele correlated with reduced forced expiratory volume in 1 second (FEV1; P=0.006). Homozygous carriers of the rs31489 C-allele exhibited increased susceptibility to bronchial obstruction with an odds ratio (OR) of 1.82 (95% confidence interval [CI]=1.24-2.69; P=0.002). A similar association was noticed for lung diffusing capacity (DLCO; P=0.004). Consistent herewith, CC-carriers had an increased risk of emphysema (OR=2.04; CI=1.41-2.94; P=1.73×10 -4 ) and displayed more alveolar destruction. Finally, CC-carriers also had an increased risk for lung cancer (OR=1.90; CI=1.21-2.99; P=0.005) and were more susceptible to develop both lung cancer and bronchial obstruction than lung cancer alone (OR=2.11; CI=1.04-4.26; P=0.038).  The rs31489 variant on 5p15.33 is associated with bronchial obstruction, the presence and severity of emphysema and lung cancer.
Antituberculosis Drug Research: A Critical Overview
Authors: None Beena, Diwan S. Rawat
Journal: Medicinal Research Reviews (2012)

Abstract The increasing drug resistance of M ycobacterium tuberculosis to the currently used drugs and HIV coinfection has caused alarm in the international scientific community. Subsequently, there is an urgent need for the development of new drug molecules with newer targets and with an alternative mechanism of action. Since the last 50 years, the same long‐duration, multidrug treatment plan is being followed for the treatment of tuberculosis. The objective of this review article is to critically analyze the antitubercular potential of various classes of compounds (quinoline, diamine, quinolone, fluoroquinolone, quinone, nitroimidazole, terpenoid, isonicotinyl, oxazolidinone, pyrimidine, and purine), their possibility to be a future drug candidate, and latest information on the clinical status of some novel antitubercular compounds. Compounds such as moxifloxacin, PA 824, and TMC 207 are well tolerated and there is no adverse effect shown by them. Moxifloxacin and gatifloxacin shows cross‐resistance to the currently used drugs while no cross‐resistance observed in case of TMC 207 and PA 824. Some compounds like OPC 67683 and PA 824 are bactericidal in nature.
Teaching English as a dead language
Authors: Colin Douglas
Journal: BMJ (2001)

Many years ago I learned English. I don't mean mother's-knee English—although I'm told that I learned that quite quickly, and grew a vocabulary from the Sunday broadsheets at an age that I'd rather keep to myself—I mean learning proper English.

I was taught for five years by a man who took it all very seriously. He had even written a book. He would plan the week's work on a Monday. (“Monday, my book. Tuesday, Keats. Wednesday, …
Effects of thixotropic maneuvers on breathing pattern and chest wall operational volumes in healthy subjects
Authors: Maria Clara Góes, Raul Felipe, Rêncio Bento Florêncio, Illia Lima, Lucien Gualdi, Andrea Aliverti, Guilherme Fregonezi
Journal: European Respiratory Journal (2014)

Respiratory muscle fibers stiffness can be temporarily reduced (Thixotropy effect) by contraction at an inflated or deflated lung volume and the stiffness returned during a resting interval (Homma et al.). The magnitude of fibers stiffness can influence the volume of chest wall and the breathing pattern. The objective of this study was to assess the effects of thixotropic maneuvers on chest wall volumes on healthy subjects. We evaluated 20 healthy subjects (23.8 ± 3.1 y) with normal lung function values by Optoeletronic Pletismography during 7 breaths after apneic, inspiratory (ThixIns) and expiratory (ThixEx) thixotropic maneuvers performed at total lung capacity (TLC) and residual volume (RV). Tidal volume showed significant decreasing trend (decreasing ΔVt) for all maneuvers performed at TLC (figure) (p  Acute effects of Thixotropy respiratory maneuvers (Apnea, Inspiratory and expiratory) performed from RV showed decreased EEV and increased tidal volume.
Intestinal Metaplasia of the Gastric Mucosa: A Gross and Microscopic Study of Its Distribution in Various Disease States&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G. N. Stemmermann, T. Hayashi
Journal: JNCI Journal of the National Cancer Institute (1968)

Gross stomach specimens may be stained to demonstrate areas of alkaline phosphatase activity. Since this is found only in parts of the mucosa showing intestinal metaplasia, it provides a new perspective for assessing this change in the stomach. The alteration was most frequent and most intense on the lesser curvature at the junction of the pylorus and corpus. The change at this site was frequently associated with a band of metaplasia on both anterior and posterior walls at the junction of the pylorus and corpus. Although metaplasia was more frequently associated with cancer than gastric ulcer, it had the same distribution when associated with either of these conditions. The most frequent site of gastric ulcer was more closely correlated with sites of maximal metaplasia than was carcinoma. Even when cancer and metaplasia coexisted, the sites of these changes did not always coincide. Microscopic analysis of the intestinal metaplasia indicated it may begin in the neck region of glands unaffected by gross injury or microscopic evidence of inflammation.
MYOCARDIAL ISCHEMIA: REPORT OF A CASE DUE TO REACTION TO TETANUS ANTITOXIN
Authors: R L CASTERLINE
Journal: Annals of Internal Medicine (1958)

Case Reports1 May 1958MYOCARDIAL ISCHEMIA: REPORT OF A CASE DUE TO REACTION TO TETANUS ANTITOXINRAY L. CASTERLINE, M.D., F.A.C.P.RAY L. CASTERLINE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-48-5-1121 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe current medical literature has been adequately documented with specific instances of profound allergic reaction to penicillin and other antimicrobial agents.1, 2This case is presented to emphasize that allergic reactions to tetanus antitoxin do occur in spite of apparently adequate testing with horse serum prior to administration of the antitoxin. These reactions, when they occur, often fit the picture of serum sickness and may involve wide areas. They are often basically vascular in nature3and capable of producing considerable injury in the areas affected by the vascular phenomena, although most of the lesions appear to be reversible. This case...Bibliography1. Von Oettingen WF: Complications of antibiotic therapy, Am. J. Med. 18: 792 (May) 1955. CrossrefMedlineGoogle Scholar2. FarberRossStephens JEJG: Antibiotic anaphylaxis, California Med. 81: 9 (July) 1954. MedlineGoogle Scholar3. Bullrich RA: Cardiovascular allergy, Bol. Acad. nac. de med. de Buenos Aires, p. 642 (Sept.) 1939. Google Scholar4. KurlandFreedberg GSAS: Potentiating effects of ACTH and cortisone on pressor response to intravenous infusion of 1-nor-epinephrine, Proc. Soc. Exper. Biol. and Med. 78: 28, 1951. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication September 10, 1956.Requests for reprints should be addressed to Ray L. Casterline, M.D., 832 East Main Street, Medford, Oregon. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug-induced cardiomyopathies 1 May 1958Volume 48, Issue 5Page: 1121-1125KeywordsAdrenocorticotropic hormoneAllergy and immunologyAntitoxinsElectrocardiographyIschemiaLesionsPenicillinTetanusUrticariaVision ePublished: 1 December 2008 Issue Published: 1 May 1958 PDF downloadLoading ...
Adjuvant Tamoxifen: Predictors of Use, Side Effects, and Discontinuation in Older Women
Authors: Serkalem Demissie, Rebecca A. Silliman, Timothy L. Lash
Journal: Journal of Clinical Oncology (2001)

To identify predictors of adjuvant tamoxifen use, side effects, and discontinuation in older women.We followed a cohort of 303 women > or = 55 years of age diagnosed with stage I or stage II breast cancer for nearly 3 years. Data were collected from women's surgical records and from computer-assisted telephone interviews at 5, 21, and 33 months after primary tumor therapy.Two hundred ninety-two (96%) of 303 patients in the study provided information about tamoxifen use. Tamoxifen use was reported by 189 patients (65%); 26 (15%) discontinued use during the follow-up period. Patients who were 65 to 74 years of age (relative to those 55 to 64 years of age), had stage II disease, were estrogen receptor-positive, saw a greater number of breast cancer physicians, and had better perceptions of their abilities to discuss treatment options with physicians had greater odds of tamoxifen use. Those who had better physical function, had received standard primary tumor therapy, and had obtained helpful breast cancer information from books or magazines had lesser odds of tamoxifen use. Patients > or = 75 years of age (relative to those 55 to 64 years of age) and patients with better emotional health had significantly lesser odds of reporting side effects. Patients who were estrogen receptor-positive were less likely to stop taking tamoxifen; patients who experienced side effects were more likely to stop taking tamoxifen.Deviations from a prescribed course of adjuvant tamoxifen occur relatively frequently. The clinical consequences of this deviation need to be identified.
Evaluating the use of the interferon-γ response to<i>Mycobacterium tuberculosis</i>-specific antigens in patients with psoriasis prior to antitumour necrosis factor-α therapy: a prospective head-to-head cross-sectional study
Authors: C.L. Martyn-Simmons, J.B. Mee, B.W. Kirkham, R.W. Groves, H.J. Milburn
Journal: British Journal of Dermatology (2012)

Targeted biological therapies have transformed the treatment of chronic inflammatory disease. However, reactivation of latent tuberculosis infection (LTBI) is a significant risk with the use of antitumour necrosis factor (anti-TNF)-α therapy and screening is mandatory prior to treatment. The tuberculin skin test (TST) may be difficult to interpret in patients with inflammatory disease or receiving immunosuppressive therapies.The aim of this study was to evaluate and compare the QuantiFERON(®) -TB Gold In-Tube (QFR) and T-SPOT.TB (TSTB) interferon-γ-release assays (IGRA) against the TST in a cohort of patients commencing anti-TNF-α therapies for chronic inflammatory disease.A prospective cross-sectional study was undertaken at a London tertiary referral centre. Demographic data collected included TB risk factors. TST, QFR and TSTB were performed in all patients.Seventy patients with chronic plaque psoriasis were included in the study. Agreement between QFR and TSTB, excluding indeterminate results, was 89% (κ = 0.567), between QFR and TST 85% (κ= 0.313) and 81% (κ = 0.244) between TSTB and TST. There was no significant association with concomitant immunosuppression and either TST or IGRA results. Seven patients received chemoprophylaxis for LTBI diagnosed after clinical risk assessment together with positive TST and/or IGRA. Three patients had positive results in all three tests.While there was moderate overall agreement between QFR and TSTB and fair correlation between TST, QFR and TSTB, there were a number of discordant results, suggesting that a three-pronged approach using TST, QFR and TSTB may be of additional benefit.
Genetic programming analysis of gene expression profiles predicts survival in pleural mesothelioma.
Authors: William P. Worzel, Craig C. Webb, Arpit Almal, Jeremy Miller, David W. Fry, Peter F. Lenehan
Journal: Clinical Cancer Research (2006)

B57  Purpose:Predicting which malignant pleural mesothelioma (MPM) patients (pts) will most likely benefit from surgical therapy is imprecise. We hypothesized that a genetic programming (GP) analysis of pretherapy tumor gene expression profiles could accurately predict survival in surgically cytoreduced MPM of all stages. Experimental Design: Tumor gene expression profiles from 20 MPM pts having cytoreductions and identical postoperative cisplatinum-based adjuvant chemotherapy were created using the Affymetrix U95A human genome array. In a supervised learning mode, GP analysis identified those gene relationships that were key predictors of survival time after surgery. A 14-pt training set and a separate 6-pt test set were created after stratifying for tumor stage and survival time. Predictive gene classifier rules, generated using the training set, were assessed for overall generality by N-fold cross validation and tested for accuracy using the test set. External validation was accomplished by utilizing a completely independent dataset of an additional 31 MPM pts from another research institution. Results: A predictive gene scoring function composed of a unique mathematical combination of 4 genes (TBX19, FOP, CCNB1, RAC1) was created that was able to correctly identify short-term (≤12 months) and long-term (>12 months) survivors in the initial test set with 83% accuracy (5 of 6 pts) based on the score produced. The same function was also able to predict and rank individual pt survival durations, in months after surgery, as the score produced correlated well (Kendall9s tau = 0.73, Pearson9s r = 0.87) with actual survival times. The same scoring function was externally validated for its ability to predict MPM pt survival using a completely independent dataset (Pearson9s r = 0.44, 2-tailed p-value = 0.013). The clinical outcomes appeared to be independent of tumor histology and reflected the heterogeneity of survival in early stage MPM pts. Conclusions: These data suggest that GP analysis of gene expression profiles from pretherapy MPM biopsies may be an accurate method for predicting which patients will most likely benefit from a surgical and adjuvant chemotherapy approach. Furthermore, by identifying recurring gene expression motifs during the process of generating candidate predictive gene classifier rules, GP might be able to suggest novel molecular interactions involved in the pathogenesis of MPM and its sensitivity to anticancer therapies that may warrant further investigation.
Impaired delivery of hemodialysis prescriptions
Authors: D W Coyne, J Delmez, G Spence, D W Windus
Journal: Journal of the American Society of Nephrology (1997)

Serial kinetic modeling is commonly used in hemodialysis to assess the adequacy of dialysis. A variety of problems lead to declining Kt/V in previously stable patients. These include noncompliance, vascular access recirculation, and dialyzer dysfunction. The purpose of this study was to find the relative frequencies of these problems in a group of patients undergoing routine hemodialysis. Simultaneous urea kinetic modeling and access recirculation were tested during 3 consecutive months. The baseline Kt/V was defined as the average of each patient's Kt/V values obtained during the previous 4 mo. A clinically important fall in Kt/V was defined as a decline of > or =0.2 if the baseline Kt/V was > or =1.2, or a decline of > or =0.1 if the baseline Kt/V was <1.2. Ninety-three of 375 (25%) sessions met the criteria for a significant decline in urea kinetic modeling. The baseline Kt/V in this group was 1.33 +/- 0.20 (mean +/- SEM) and declined to 1.02 +/- 0.18 in the abnormal month (P < 0.05). In 42% of instances with a decline of Kt/V, reduced blood processing due to a lower blood flow or shorter time than prescribed was responsible. Recirculation of >12% was found in 25% of sessions with a decrease in Kt/V. These patients most often had access dysfunction or reversed needles. The remaining one-third of patients with decreases in Kt/V had no problem identified, and subsequent monthly kinetic modeling results returned to baseline. These results suggest that analysis of falling urea kinetic modeling results should include a careful review of the dialysis record for reductions in prescribed time or blood flow rates followed by vascular access testing. If these evaluations are unrevealing, urea kinetic modeling results usually return to baseline in the next month.
Karyotypic and Morphologic Characterization of a Serially Transplanted Human Choriocarcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Michael Galton, Peter B. Goldman, Sarah F. Holt
Journal: JNCI Journal of the National Cancer Institute (1963)

A human choriocarcinoma adapted to serial passage in the wall of the cheek pouch of the agouti Syrian (golden) hamster was found to possess an unstable and irregular aneuploid karyotype with a modal value of 80 rising to 88–92 after 9 months. The species of origin of the tumor was established as at least predominantly human by several criteria: 1) grouping the chromosomes of individual cells on a morphologic basis yielded a distribution similar to the pattern of the normal human karyotype; 2) prominent satellites, similar to those associated with normal human acrocentric chromosomes, were often present on tumor acrocentric chromosomes; 3) there was an increase, in proportion to the ploidy, in the number of the smaller chromosomes, a feature consistent with the situation in heteroploid tumors of human origin; and 4) the tumor cells displayed a degree of mitotic arrest in response to colchicine compatible with the known sensitivity of human cells to this agent. The morphology of the tumor is described; it remained unchanged during the year of observation, despite the karyotypic instability. The administration of dehydroisoandrosterone, a possible precursor of estrone, led to the increased formation of syncytio-trophoblast, the tissue believed responsible for estrogen production by the placenta.
A comparison of cause of death between patients treated with hemodialysis and peritoneal dialysis.
Authors: W E Bloembergen, F K Port, E A Mauger, R A Wolfe
Journal: Journal of the American Society of Nephrology (1995)

Mortality rates associated with peritoneal dialysis (PD) have been found to be higher than those associated with hemodialysis (HD) among prevalent U.S. patients over the age of 55 in the preceding study. Given the substantial technical differences between PD and HD, causes of death might also be expected to differ between these dialytic modalities. In order to help elucidate the relative contributions of these technical differences and to further the understanding of the excess mortality observed among PD-treated dialysis patients, this epidemiologic study compared cause of death in prevalent HD- and PD-treated patients in a large national sample, adjusting for demographic characteristics. Data for patients prevalent on January 1 of the years 1987, 1988, and 1989, each with 1 yr of follow-up, were obtained from the U.S. Renal Data System. Patients were censored at transplantation. Death rates per 100 patient years for seven cause-of-death categories were compared between HD and PD, adjusting for age, race, gender, cause of ESRD (diabetes versus nondiabetes), and < 1 yr or > 1 yr of prior ESRD, by use of the Poisson regression. There were 42,372 deaths occurring over 170,700 patient years at risk. There was a significantly increased mortality risk for PD compared with HD for all cause-of-death categories, except malignancy, for which there was a higher mortality risk for HD. The excess all-cause mortality observed in PD-treated patients can be accounted for, in decreasing order, by infection (35%), acute myocardial infarction (24%), other cardiac causes (16%), cerebrovascular disease (8%), withdrawal (8%), and malignancy (-6%).(ABSTRACT TRUNCATED AT 250 WORDS)
Are metabolomic markers associated with spirometric lung function indices
Authors: Claudia Flexeder, Stefan Karrasch, Gabi Kastenmüller, Christa Meisinger, Ann-Kristin Petersen, Elisabeth Thiering, Cornelia Prehn, Rui Wang-Sattler, Stephan Weidinger, Christian Gieger, Joachim Heinrich, Rolf Holle, Annette Peters, Thomas Illig, Jerzy Adamski, Karsten Suhre, Holger Schulz
Journal: European Respiratory Journal (2014)

Background: Respiratory function shows a large interindividual variability which is related to genetic, developmental and environmental factors. These determinants influence an individual's metabolism, but little is known about metabolic processes and lung function.

Objective: To investigate the association between lung function and metabolite concentrations in adults from a population-based study.

Methods: Spirometry was performed in a subpopulation of the KORA-F4 cohort (1321 subjects aged 41-62 years). In fasting blood samples, over 650 metabolites were determined on two different mass spectrometry based metabolomic platforms. Linear regression models were calculated for each metabolite after adjustment for age, sex, smoking, BMI and batch effects, and the residuals of these models were used to assess associations between metabolites and percent predicted (pp) values of FEV1 and FVC.

Results: We identified 30 metabolites that were significantly associated with lung function indices after correction for multiple testing (q-values ranged from 4.9•10-2 to 3.3•10-4). Of these metabolites, 29 were associated with FVCpp and 23 were associated with FEV1pp. These indices are linked to different metabolites involved in lipid metabolism, tocopherol metabolism and tyrosine metabolism. An association with the xenobiotic pathway was also observed.

Conclusion: The lipid metabolites identified suggest pulmonary surfactant is involved in lung function, as surfactant is mainly composed of different phospholipids and is vital for the facilitation of peripheral air spaces. The observed association with tocopherol metabolism may suggest an importance of antioxidant or anti-inflammatory defence for respiratory function.
Early oxygen desaturation is related to acute mountain sickness (AMS) development during acute high altitude (HA) exposure
Authors: Gaia Mandolesi, Luca Pomidori, Giovanni Avancini, Eva Bernardi, Manuela Bartesaghi, Annalisa Cogo
Journal: European Respiratory Journal (2012)

Early oxygen desaturation during HA exposure (both in the field and during HA simulated test) has been reported to be significantly related to AMS development.

Aim 

Aim: monitor oxygen saturation (SpO2) and AMS during the ascent from Alagna (1200m) to Capanna Regina Margherita (4559m) with an overnight stay in Gnifetti Hut (3647m).

Methods 

66 subjects (55M, 18-67 yrs), intending to climb M. Rosa, were recruited at the cable care station in Alagna, equipped with a 24-h data memory pulse oximeter (Pulsox-3Si, Minolta) and asked to fill the Lake Louise questionnaire for AMS diagnosis. 25 subjects (37.8%) showed a LL score ≥3 (AMS+ group), 41 were in AMS-group.

Results 

SpO2% in AMS+ and AMS- was similar in Alagna (94.6±1.9 vs 95.1±1.2 n.s.) but lower in AMS+ during HA exposure: at 3275m, after 30-45 min. of cable car (85.5±4.1 vs 87.7±3.5,*); in Gnifetti Hut at rest (84.5±2.3 vs 86.4±2.4, **) and during the night (76.9±4.6 vs 79.5±3.7,*). AMS+ spent more time with lower SpO2: time (%) at rest in Gnifetti Hut with SpO2%   time (hours) spent with SpO2 %<80 and 75 (3.5±1.2 vs 2.7±0.9, *; 2.5±1.4 vs 1.5±0.8,*). [* p< 0.05, ** p< 0.01]

Conclusions 

Lower SpO2 in AMS + occurs very early at the beginning of HA exposure after 30-40 min. of ascent. Subjects which subsequently develop AMS always spend more time with SpO2 significantly lower than healthy subjects (AMS-).