tbuckley/cabot-search huggingface dataset:
Risk of Contralateral Testicular Cancer: A Population-based Study of 29 515 U.S. Men
Authors: Sophie D. Fosså, Jinbo Chen, Sara J. Schonfeld, Katherine A. McGlynn, Mary L. McMaster, Mitchell H. Gail, Lois B. Travis
Journal: JNCI Journal of the National Cancer Institute (2005)

Although risk estimates for synchronous and metachronous contralateral testicular cancers vary widely, many clinicians recommend routine biopsy of the contralateral testis for patients diagnosed with unilateral testicular cancer. We evaluated the risk of contralateral testicular cancer and survival in a large population-based cohort of men diagnosed with testicular cancer before age 55 years.For 29 515 testicular cancer cases reported to the National Cancer Institute's Surveillance, Epidemiology and End Results Program from 1973 through 2001, we estimated the prevalence of synchronous contralateral testicular cancer, the observed-to-expected ratio (O/E) and 15-year cumulative risk of metachronous contralateral testicular cancer, and the 10-year overall survival rate of both synchronous and metachronous contralateral testicular cancer, using the Kaplan-Meier method for the two latter assessments. Age-adjusted multivariable analyses were used to examine risk according to histologic type of the original cancer.A total of 175 men presented with synchronous contralateral testicular cancer; 287 men developed metachronous contralateral testicular cancer (O/E = 12.4 [95% confidence interval {CI} = 11.0 to 13.9]; 15-year cumulative risk = 1.9% [95% CI = 1.7% to 2.1%]). In the multivariable analysis, only nonseminomatous histology of the first testicular cancer was associated with a statistically significantly decreased risk of metachronous contralateral testicular cancer (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.46 to 0.79; P<.001). Increasing age at first testicular cancer diagnosis was associated with decreasing risk of nonseminomatous metachronous contralateral testicular cancer (odds ratio = 0.90, 95% CI = 0.86 to 0.94). The 10-year overall survival rate after metachronous contralateral testicular cancer diagnosis was 93% (95% CI = 88% to 96%), and that after synchronous contralateral testicular cancer was 85% (95% CI = 78% to 90%).The low cumulative risk of metachronous contralateral testicular cancer and favorable overall survival of patients diagnosed with metachronous contralateral testicular cancer is in accordance with the current U.S. approach of not performing a biopsy on the contralateral testis.
Potassium channel down-regulation in heart failure
Authors: M Näbauer
Journal: Cardiovascular Research (1998)

Prolongation of action potential duration is the most consistent electrophysiological abnormality in myocardium and myocytes from hypertrophied and failing hearts. Measurements of currents in myocytes from hypertrophied and failing hearts indicate that, in most cases, this is due to a decrease in outward potassium currents. If present, a calcium-independent transient outward current is usually substantially reduced, but delayed rectifier and inward rectifier currents have also been found to be diminished. There is increasing evidence that potassium current down-regulation contributes significantly to the enhanced lability of the repolarization process in heart failure, predisposing to early after-depolarizations, dispersion of repolarization and ventricular arrhythmias. The reduction of outward potassium currents may also be involved in the enhanced sensitivity of failing myocardium to triggering factors like hypokalemia, ischemia, and antiarrhythmic agents with Class III effects. A thorough understanding of the mechanisms of cardiac excitability and arrhythmogenesis at the cellular and molecular level under normal and pathological conditions will be essential for the development of new pharmacological strategies to prevent sudden cardiac death in heart failure.
Impact of endoscopic biopsy surveillance of Barrett’s oesophagus on pathological stage and clinical outcome of Barrett’s carcinoma
Authors: J W van Sandick, J J B van Lanschot, B W Kuiken, G N J Tytgat, G J A Offerhaus, H Obertop
Journal: Gut (1998)

The efficacy of endoscopic biopsy surveillance of Barrett's oesophagus in reducing mortality from oesophageal cancer has not been confirmed.To investigate the impact of endoscopic biopsy surveillance on pathological stage and clinical outcome of Barrett's carcinoma.A clinicopathological comparison was made between patients who initially presented with oesophageal adenocarcinoma (n = 54), and those in whom the cancer had been detected during surveillance of Barrett's oesophagus (n = 16).The surveyed patients were known to have Barrett's oesophagus for a median period of 42 months (range 6-144 months). Prior to the detection of adenocarcinoma or high grade dysplasia, 13 to 16 patients (81%) were previously found to have low grade dysplasia. Surgical pathology showed that surveyed patients had significantly earlier stages than non-surveyed patients (p = 0.0001). Only one surveyed patient (6%) versus 34 non-surveyed patients (63%) had nodal involvement (p = 0.0001). Two year survival was 85.9% for surveyed patients and 43.3% for non-surveyed patients (p = 0.0029).The temporal course of histological progression in our surveyed patients supports the theory that adenocarcinoma in Barrett's oesophagus develops through stages of increasing severity of dysplasia. Endoscopic biopsy surveillance of Barrett's oesophagus permits detection of malignancy at an early and curable stage, thereby potentially reducing mortality from oesophageal adenocarcinoma.
Salivary steroid hormone response in trained men to running and circuit training sessions
Authors: A Tanner, B Nielsen, J Tetteh, J Allgrove
Journal: British Journal of Sports Medicine (2011)

Cortisol (C) and testosterone (T) are important biomarkers of acute and chronic stress (Urhausen et al . Sports Med 1995; 20 :251–76). However, it is unclear how different forms of training affect the response of these hormones. The purpose of this study was to examine the effect of various training sessions on salivary C and T in competitive male runners. Four trials were completed: (a) 30 min tempo run at lactate threshold (TEMP); (b) 30 min running alternating 3.5 min at 90% and 2 min at 30% VO 2 max (INT); (c) 30 min circuit training with 3×10 exercises of 30 s with 30 s recovery between exercises (CIR) and d) 30 min rest (REST). Saliva samples were collected pre exercise and at 0, 15, 30 and 60 min post exercise and rating of perceived exertion (RPE) and heart rate (HR) were recorded. All samples were analysed with ELISA and salivary C was also measured with mass spectrometry. Preliminary data shows mean HR was: 161 ± 7, 159 ± 14, 130 ± 12 and 63 ± 1 beats per min for TEMP, INT, CIR and REST respectively with INT and TEMP higher than REST. RPE was: 15 ± 1, 16 ±2 and 13 ±1 for TEMP, INT and CIR respectively, INT was higher than CIR and TEMP. There was a difference in salivary C between the trials (p=0.038) and between time points (p=0.019). Area under curve (AUC) analysis indicated salivary C was higher than REST in INT (P=0.043) and TEMP (0.043) with INT showing the highest response (p=0.046). Salivary T showed an overall effect of time (p=0.024) with post exercise T higher than pre exercise (p=0.020). INT also showed a higher T response than REST (p=0.003) and TEMP tended to be higher (p=0.054). Salivary Peak HR correlated with peak salivary T for INT (r=0.961). This study implies an INT session increased salivary C and T more than TEMP and CIR despite no differences in mean HR, also peak HR may be linked to salivary T production which could be a useful to assess training stress.
Multidimensional assessment and tailored interventions for COPD: respiratory utopia or common sense?
Authors: Vanessa M McDonald, Isabel Higgins, Lisa G Wood, Peter G Gibson
Journal: Thorax (2013)

<h3>Introduction</h3> The rising disease burden from chronic obstructive pulmonary disease (COPD) requires new approaches. <h3>Method</h3> We suggest an approach based around three elements: inflammometry and multidimensional assessment to identify therapeutic targets and case management to design and implement an individualised treatment programme based on these assessments. <h3>Discussion</h3> This tailored approach to treatment would maximise efficacy, limit cost and permit a better risk–benefit ratio of treatment. The advantages include the ability to add up the benefits of individual therapies leading to a cumulative therapeutic benefit that is greater than each individual therapy alone. We can now design a multifaceted inflammometry intervention for airway diseases based on targeting eosinophilic inflammation, non-eosinophilic pathways and systemic inflammation. COPD is a complex and challenging disease. The use of inflammometry and multidimensional assessment is necessary to identify relevant treatment targets and maximise the scope of therapy while limiting unnecessary use of drugs. An individualised programme of management can be designed and coordinated by using a case manager. This new approach may provide tangible benefits to people with COPD.
ON THE TREATMENT OF THE POOR
Authors: JOE YAMAMOTO, MARCIA KRAFT GOIN
Journal: American Journal of Psychiatry (1965)

The poor patient with his special needs requires special psychiatric treatment. In the past, clinics have not considered this fact and have rejected them too often as unsuitable or unmotivated. We have learned some treatment techniques in listening to our patients and in considering the contributions of others. Thus we have developed techniques for a flexible, active, brief, supportive and reality-oriented treatment approach. These techniques include changes in administrative procedures such as appointment scheduling and in efforts to create a warm, friendly social context in which to offer help. We have modified group therapy and have focused on not only insight but education, social interaction and group support. Minimal supportive therapy with drugs as indicated serves a portion of our patient population. With all these changes, the responses of our patients have been much more often enthusiastic than those of our professional colleagues. We trust that with experience they will also see the efficacy of treatment specifically planned for these poor patients.
Impact of obstructive sleep apnea treatment by continuous positive airway pressure on cardiometabolic biomarkers: A systematic review from sham CPAP randomized controlled trials
Authors: Ingrid Jullian-Desayes, Marie Joyeux-Faure, Renaud Tamisier, Sandrine Launois, Anne-Laure Borel, Patrick Levy, Jean-Louis Pepin
Journal: Sleep Medicine Reviews (2014)
Single Nucleotide Polymorphism in the Mutational Hotspot of <i>WT1</i> Predicts a Favorable Outcome in Patients With Cytogenetically Normal Acute Myeloid Leukemia
Authors: Frederik Damm, Michael Heuser, Michael Morgan, Haiyang Yun, Anika Großhennig, Gudrun Göhring, Brigitte Schlegelberger, Konstanze Döhner, Oliver Ottmann, Michael Lübbert, Wolfgang Heit, Lothar Kanz, Günter Schlimok, Aruna Raghavachar, Walter Fiedler, Hartmut Kirchner, Hartmut Döhner, Gerhard Heil, Arnold Ganser, Jürgen Krauter
Journal: Journal of Clinical Oncology (2009)

We assessed the prognostic impact of a known single nucleotide polymorphism (SNP) located in the mutational hotspot of WT1 in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers.WT1 exons 7 and 9 from 249 CN-AML patients from multicenter treatment trials AML-SHG Hannover 0199 (Clinical Trials Identifier NCT00209833) and 0295, and 50 healthy volunteers were analyzed by direct sequencing. NPM1, FLT3, CEBPA, and MLL were assessed for mutations and WT1 expression was quantified.The minor allele of SNP rs16754 (WT1(AG/GG)) was found in 25.7% of CN-AML patients' blasts and germline DNA and in 36% of healthy volunteers. Patient characteristics, frequencies of mutations, or WT1 expression levels were similarly distributed between patients homozygous for the major allele compared with patients heterozygous or homozygous for the minor allele. SNP rs16754 status was an independent predictor of relapse-free survival (RFS; hazard ratio [HR], 0.49; 95% CI, 0.3 to 0.81; P = .005) and overall survival (OS; HR, 0.44; 95% CI, 0.27 to 0.74; P = .002) in multivariate analysis. The favorable effect of SNP rs16754 was stronger in NPM1/FLT3-ITD (internal tandem duplication of the FLT3 gene) high-risk patients compared with NPM1/FLT3-ITD low-risk patients. Favorable prognosis could not be identified by any other known low-risk marker in half the patients with at least one minor allele (13% of all patients). No difference for complete remission rate, RFS, or OS was found between patients with or without acquired WT1 mutations.WT1 SNP rs16754 may be a novel independent favorable-risk marker in CN-AML patients that might improve risk and treatment stratification.
Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study
Authors: B. Iacopetta, A. Russo, V. Bazan, G. Dardanoni, N. Gebbia, T. Soussi, D. Kerr, H. Elsaleh, R. Soong, D. Kandioler, E. Janschek, S. Kappel, M. Lung, C.-S.S. Leung, J.M. Ko, S. Yuen, J. Ho, S.Y. Leung, E. Crapez, J. Duffour, M. Ychou, D.T. Leahy, D.P. O'Donoghue, V. Agnese, S. Cascio, G. Di Fede, L. Chieco-Bianchi, R. Bertorelle, C. Belluco, W. Giaretti, P. Castagnola, E. Ricevuto, C. Ficorella, S. Bosari, C.D. Arizzi, M. Miyaki, M. Onda, E. Kampman, B. Diergaarde, J. Royds, R.A. Lothe, C.B. Diep, G.I. Meling, J. Ostrowski, L. Trzeciak, K. Guzińska-Ustymowicz, B. Zalewski, G.M. Capellá, V. Moreno, M.A. Peinado, C. Lönnroth, K. Lundholm, X.F. Sun, A. Jansson, H. Bouzourene, L.-L. Hsieh, R. Tang, D.R. Smith, T.G. Allen-Mersh, Z.A.J. Khan, A.J. Shorthouse, M.L. Silverman, S. Kato, C. Ishioka
Journal: Annals of Oncology (2006)
So inhaled steroids slow the rate of decline of FEV1 in patients with COPD after all?
Authors: P S Burge
Journal: Thorax (2003)

Meta-analyses show that inhaled steroids are helpful in COPD

The medical community has made up its mind that, although inhaled corticosteroids reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD),1 they do not affect disease progression.2 Despite measurement of forced expiratory volume in one second (FEV1) being widely available and a strong predictor of mortality,3 the emphasis has moved to softer outcome measures which do show changes with available treatments. Ten years ago many of us had different beliefs—several small studies using simple statistics suggested that the rate of decline in FEV1 could be reduced by about 20 ml a year by inhaled corticosteroids.4–6 This led to several large studies, the primary outcome of which was decline in FEV1 and which were powered to detect a 20 ml/year difference between active and placebo treatments.7–10 All failed to show significant differences in their primary outcome of FEV1 decline between various inhaled corticosteroids and placebo.

In this issue Sutherland and colleagues have done a meta-analysis of those trials, and have shown that inhaled corticosteroids do slow the decline in FEV1 significantly.11 How should we respond to this meta-analysis? Are the differences found clinically meaningful? Was there anything wrong with our original hypotheses or analyses? And what should we make of a similar meta-analysis that appeared to come to opposite conclusions?12

Despite the lack of clinical licences, inhaled corticosteroids have been widely prescribed for patients with COPD. In some parts of the world more that 50% of patients were receiving these drugs “off licence” by the mid 1990s.8,13 This has allowed various database studies to estimate the effect on mortality of prescribing inhaled corticosteroids.

There are problems in adequately controlling for confounders in non-randomised studies; despite …
Genome-wide association scan in north Indians reveals three novel HLA-independent risk loci for ulcerative colitis
Authors: Garima Juyal, Sapna Negi, Ajit Sood, Aditi Gupta, Pushplata Prasad, Sabyasachi Senapati, Jacques Zaneveld, Shalini Singh, Vandana Midha, Suzanne van Sommeren, Rinse K Weersma, Jurg Ott, Sanjay Jain, Ramesh C Juyal, B K Thelma
Journal: Gut (2014)

<h3>Objective</h3> Over 100 ulcerative colitis (UC) loci have been identified by genome-wide association studies (GWASs) primarily in Caucasians (CEUs). Many of them have weak effects on disease susceptibility, and the bulk of the heritability cannot be ascribed to these loci. Very little is known about the genetic background of UC in non-CEU groups. Here we report the first GWAS on UC in a genetically distinct north Indian (NI) population. <h3>Design</h3> A genome-wide scan was performed on 700 cases and 761 controls. 18 single-nucleotide polymorphisms (SNPs) (p&lt;5×10<sup>−5</sup>) were genotyped in an independent cohort of 733 cases and 1148 controls. A linear mixed model was used for case–control association tests. <h3>Results</h3> Seven novel human leucocyte antigen (HLA)-independent SNPs from chromosome 6, located in 3.8-1, <i>BAT2</i>, <i>MSH5</i>, <i>HSPA1L</i>, <i>SLC44A4</i>, <i>CFB</i> and <i>NOTCH4</i>, exceeded p&lt;5×10<sup>−8</sup> in the combined analysis. To assess the independent biological contribution of such genes from the extended HLA region, we determined the percentage alternative pathway activity of complement factor B (<i>CFB</i>), the top novel hit. The activity was significantly different (p=0.01) between the different genotypes at rs12614 in UC cases. Transethnic comparisons revealed a shared contribution of a fraction of UC risk genes between NI and CEU populations, in addition to genetic heterogeneity. <h3>Conclusions</h3> This study shows varying contribution of the HLA region to UC in different populations. Different environmental exposures and the characteristic genetic structure of the HLA locus across ethnic groups collectively make it amenable to the discovery of causative alleles by transethnic resequencing. This may lead to an improved understanding of the molecular mechanisms underlying UC.
Patterns of second primary malignancy risk in multiple myeloma patients before and after the introduction of novel therapeutics
Authors: P Razavi, K A Rand, W Cozen, A Chanan-Khan, S Usmani, S Ailawadhi
Journal: Blood Cancer Journal (2013)

Recent studies have reported an increased risk of second primary malignancies (SPM) following multiple myeloma (MM) diagnosis associated with novel anti-myeloma treatments. We evaluated the risk of SPM among 36 491 MM cases reported to the Surveillance, Epidemiology, and End Results program (SEER) between 1973 and 2008. We calculated overall and site-specific standardized incidence ratio (SIR) and 95% confidence intervals (CI) for 2012 SPM cases diagnosed within the 35-year follow-up. There was no significant overall risk of SPM (SIR=0.98; 95% CI=0.94-1.02); however, there were multiple site-specific risk patterns. The risk of breast and prostate cancer was significantly decreased overall and across age, latency and the year of diagnosis strata. There was an ∼50% increased risk of colorectal cancer 5 years after MM diagnosis (Ptrend<0.001). The risk of hematological malignancies was significantly increased, notably for acute myeloid leukemia (AML; SIR=6.51; 95% CI=5.42-7.83). There was a significant decreasing trend for AML over time, particularly for patients 65. However, no significant change in risk was noted after the introduction of autologous stem cell transplant among younger patients (<65 years). On the basis of observed trends for overall SPM as well as AML, no association between the introduction of novel therapies and SPM following MM has emerged in this large population-based study.
How we diagnose and treat iron deficiency anemia
Authors: Michael Auerbach, John W. Adamson
Journal: American Journal of Hematology (2015)

It is estimated that one-third of the world's population is anemic, the majority being due to iron deficiency (ID). In adults, ID is associated with fatigue in the absence of anemia, restless legs syndrome, pica and, in neonates, delayed growth and development. In adolescents, ID is associated with decrements in learning and behavioral abnormalities. In the absence of a clear cause, search for a source of bleeding is indicated. No single test is diagnostic of ID unless the serum ferritin is low or the percent transferrin saturation is low with an elevated total iron binding capacity. Oral iron is considered front line therapy except for conditions such as gastric bypass, heavy uterine bleeding, inflammatory bowel disease, and hereditary hemorrhagic telangiectasia. Oral iron has many unpleasant side effects, resulting in low patient adherence. For patients intolerant of, or unresponsive to, oral iron, intravenous (IV) administration is the preferred route. While early formulations were associated with a high incidence of serious adverse events (SAEs), newer formulations are much safer with SAEs occurring very infrequently. Full replacement doses can be administered in a matter of minutes to a few hours. Nevertheless, there remains a reluctance to use IV iron due to a misunderstanding of the safety of the available formulations. IV iron is safe and effective in all clinical circumstances including pregnancy. The preponderance of published evidence suggests IV iron therapy is underutilized and we believe that IV iron should be moved forward in the treatment of ID and iron deficiency anemia (IDA).
Dust from carpeted and smooth floors: IV. Solid material, proteins and allergens collected in the different filter stages of vacuum cleaners after ten days of use in schools.
Authors: T. DYBENDAL, W. C. WEDBERG, S. ELSAYED
Journal: Allergy (1991)

The accumulation of dust, proteins and allergens from alder, birch, timothy, cat, dog, mite, hen egg white, codfish and mould in schools was investigated by analysing the content of vacuum cleaners after 10 days of use. The main goals were to compare the dust accumulation on carpeted and smooth floors and to estimate to what degree the three vacuum cleaner filter stages (i.e. the disposable bag, the main filter and the microfilter) collected dust, proteins and allergens. Carpeted floors accumulated more dust, proteins and allergens per unit area than smooth floors. Histamine release studies of some of the dust extracts showed that the dust from carpeted floors released histamine from passively sensitized basophils at concentrations for which dust from smooth floors gave low or no histamine release. The analyses showed that most of the dust, proteins and allergens were retained in the dust bags. Less than 1% of the vacuumed material had accumulated in the main filters, which, according to the manufacturer, detain 99.5% of particles greater than 2 microns. By the use of a scanning electron microscope (SEM), particle deposits were observed in the microfilters. These deposits, which represented less than 0.1% of the total mass, showed no significant allergenic activity. Thus, for the field conditions of this study, the microfilters were not needed for cleaning the exit air of allergens, although they were useful for removing fine (less than 2 microns) particles.