tbuckley/cabot-search huggingface dataset:
Pre-immigration screening process and pulmonary tuberculosis among Ethiopian migrants in Israel
Authors: Z. Mor, Y. Lerman, A. Leventhal
Journal: European Respiratory Journal (2008)

More than 75,000 displaced Ethiopians have moved to Israel. Tuberculosis (TB) incidence in Ethiopia is 44 times higher than in Israel (344 versus 8 cases per 100,000 inhabitants, respectively). The aims of the present retrospective cohort study were to evaluate the pre-immigration screening process initiated in 2001 on pulmonary TB (PTB) morbidity and to assess its cost-effectiveness. Ethiopian immigrants who were screened before departure (study group) were compared with those who were screened after arrival (comparison group). Between 1998 and 2005, 24,051 Ethiopian immigrants arrived in Israel. PTB was diagnosed in 332 (1.4%) immigrants, an incidence density of 325 patients per 100,000 person-yrs. PTB cumulative incidence was lower in the study group than in the comparison group: 711 compared with 1,746 patients per 100,000 immigrants, respectively (rate ratio 0.4). PTB was detected significantly earlier in the study group than in the comparison group: 193 versus 487 days after entry, respectively. Disease incidence declined significantly during the first 2 yrs following immigration. A 5-yr predictive model indicated that 98 individuals would be free of PTB, saving US$91,055 on annual treatment cost, due to screening. The pre-immigration screening process reduced pulmonary tuberculosis incidence in subsequent years following immigration. Pulmonary tuberculosis was diagnosed earlier in the screened group than in the comparison group and the process was found to be both cost-beneficial and cost-effective.
Remission of respiratory symptoms by smoking and occupational exposure in a cohort study
Authors: T.M.L. Eagan, A. Gulsvik, G.E. Eide, P.S. Bakke
Journal: European Respiratory Journal (2004)

Few studies have estimated the remission rates of respiratory symptoms in general populations. No community cohort studies have examined the impact of smoking cessation and previous dust or fumes exposure on the remission of respiratory symptoms. In the Hordaland County Study, an 11-yr community cohort (1985-1996/1997) from Western Norway, data from 2,819 subjects were used to examine the remission of six respiratory symptoms. The measured cumulative remission varied from 42.3% for morning cough to 58.4% for chronic cough. Smoking cessation was a significant predictor of remission of the cough symptoms and wheezing, with odds ratios (OR) (95% confidence intervals (CI)) varying from 2.2 (1.3-3.7) for wheezing to 6.2 (3.5-11.2) for morning cough, after adjustment for sex, age, pack-years smoked, previous dust or fumes exposure, and educational level. In those not previously exposed to dust or fumes, the adjusted OR (95% CI) for the remission of morning cough, phlegm cough, dyspnoea grade 2, attacks of dyspnoea and wheezing varied from 1.5 (0.9-2.5) for attacks of dyspnoea to 2.1 (1.1-3.9) for dyspnoea grade 2, as compared to those previously exposed to dust or fumes. This study suggests a beneficial effect of smoking cessation and an adverse effect of occupational exposure on the remission of respiratory symptoms.
T-cell receptor repertoire expression in workers with occupational asthma due to platinum salt
Authors: M Raulf-Heimsoth, R Merget, HP Rihs, M Fohring, V Liebers, B Gellert, G Schultze-Werninghaus, X Baur
Journal: European Respiratory Journal (2000)

There is a high incidence of asthma, rhinitis, conjunctivitis and contact urticaria in workers of precious metal refineries. Symptoms are closely associated with sensitization to halogenated platinum compounds, as assessed by skin-prick test. The aim of the present study was to examine the molecular mechanisms involved by describing the T-cell receptor (TCR) repertoire distribution of peripheral blood mononuclear cells (PBMCs) without and after in vitro stimulation with sodium hexachloroplatinate. PBMCs of 17 sensitized subjects with work-related asthma and a positive skin-prick test result to sodium hexachloroplatinate and of 15 nonexposed subjects were isolated and TCR expression determined by flow cytometry. Furthermore, the sodium hexachloroplatinate-mediated in vitro effects on the frequency of Vbeta-expressing T-cells, the proliferation response and the expression of cell surface molecules like CD71, CD25, CD95 and HLA-DR were studied. CD3-positive lymphocytes of platinum salt-sensitized workers had a significantly higher frequency of Valpha2a+, Vbeta11+ and Vbeta21.3+ T-cells than controls (p&lt;0.01, p&lt;0.01 and p&lt;0.001 respectively). In vitro stimulation of PBMCs from platinum salt-sensitized as well as control subjects with sodium hexachloroplatinate increased the percentage of CD3-positive cells bearing specific TCRs, especially Vbeta5.3, Vbeta6.7, Vbeta8a, Vbeta20 and Vbeta21.3. This effect was time- and dose-dependent. The present results indicate that the frequencies of Valpha2a-, V11 and Vbeta21.3-bearing blood T-cells and platinum salt-induced lymphocyte proliferation are strongly enhanced in subjects who suffer from asthma due to platinum salt. In addition, in vitro stimulation with sodium hexachloroplatinate modulates the frequencies of certain T-cell receptor-bearing T-cells.
Investigating infant deaths
Authors: M P Ward Platt
Journal: BMJ (2005)

Where next?Identifying more breast cancers at earlier stages with "good prognosis" can make decisions about appropriate adjuvant treatment more complex, bringing a real risk of relative overtreatment of some women.This could be particularly important in lymph node negative and steroid hormone receptor positive breast cancer.Better understanding of the gene expression signatures of breast cancers may lead to new classifications that may have both prognostic and predictive information. 11A trial is already investigating this approach in premenopausal women, comparing selection by microarray signature against conventional criteria. 12Finally, while the work discussed here highlights the improvements in survival from breast cancer attributable to systemic therapy and diagnosis of small, node negative tumours, neither approach affects incidence.The diagnosis of breast cancer, even with a supposedly good prognosis, can be devastating, and we should not lose sight of primary prevention as a real goal.
Brain cholecystokinin and nutritional status in rats and mice.
Authors: B S Schneider, J W Monahan, J Hirsch
Journal: Journal of Clinical Investigation (1979)

Under certain conditions, exogenously administered cholecystokinin (CCK) or its COOH-terminal octapeptide can terminate feeding and cause behavioral satiety in animals. Furthermore, high concentrations of CCK are normally found in the brains of vertebrate species. It has thus been hypothesized that brain CCK plays a role in the control of appetite. To explore this possibility, a COOH-terminal radioimmunoassay was used to measure concentrations of CCK in the cerebral cortex, hypothalamus, and brain stem of rats and mice after a variety of nutritional manipulations. CCK, mainly in the form of its COOH-terminal octapeptide, was found to appear in rat brain shortly before birth and to increase rapidly in cortex and brain stem throughout the first 5 wk of life. Severe early undernutrition had no effect on the normal pattern of CCK development in rat brain. Adult rats deprived of food for up to 72 h and rats made hyperphagic with highly palatable diets showed no alterations in brain CCK concentrations or distribution of molecular forms of CCK as determined by Sephadex gel filtration of brain extracts. Normal CCK concentrations were also found in the brains of four strains of genetically obese rodents and in the brains of six animals made hyperphagic and obese by surgical or chemical lesioning of the ventromedial hypothalamus. It is concluded that despite extreme variations in the nutritional status of rats and mice, CCK concentrations in major structures of the brain are maintained with remarkable constancy.
Synergistic Effect of Double-Stranded RNA and TGF-α on MUC5AC production in Human Bronchial Epithelial Cells
Authors: H. Tadaki, H. Arakawa, T. Mizuno, T. Suzuki, H. Mochizuki, K. Tokuyama, A. Morikawa
Journal: Journal of Allergy and Clinical Immunology (2007)
Dysphonia caused by inhaled steroids: recognition of a characteristic laryngeal abnormality.
Authors: A J Williams, M S Baghat, D E Stableforth, R M Cayton, P M Shenoi, C Skinner
Journal: Thorax (1983)

Nine of 14 asthmatic patients who presented with persistent dysphonia while taking inhaled corticosteroids had a bilateral adductor vocal cord deformity with bowing of the cords on phonation. This causes the dysphonia and usually occurs without candidiasis. It was seen with beclomethasone dipropionate (in both pressurised aerosol and dry powder preparations), betamethasone valerate, and budesonide. It was related to the dose and potency of inhaled steroid and may represent a local steroid myopathy. It was reversed when the inhaled steroid was stopped, although resolution sometimes took weeks. Laryngeal candidiasis may have contributed to the vocal cord abnormality in two of these nine patients. Of the five patients without vocal cord deformity, laryngeal candidiasis was the sole cause of dysphonia in three. In the remaining two dysphonia was thought to be psychogenic. The vocal cord deformity may exist subclinically. Of nine patients who started to take aerosol steroid and who were examined monthly for one year, three developed vocal cord deformity but only one had persistent dysphonia. Vocal abuse did not appear to contribute to dysphonia.
The Detection of Asymptomatic Coronary Artery Disease
Authors: V F Froelicher
Journal: Annual Review of Medicine (1977)

In summary, near-maximal or maximal exercise testing has a sensitivity of approximately 60% and a specificity of approximately 90% for coronary atherosclerotic heart disease. When screening asympatomatic men with exercise testing, an abnormal response identifies a group of men at very high risk for coronary artery disease. However, the predictive value limitations are obvious and the false-positive problem must be realized. At present, there is no second line of noninvasive studies that can separate an exercise-test false positive from a true positive with certainty. Risk-factor consideration may help separate them; The sensitivity limitations of exercise testing must be especially considered when evaluating people at high risk for CAD. An abnormal test response does not absolutely predict the presence of CAD and a normal response does not rule out its possibility. In appropriate instances where coronary angiography can be performed at minimal risk and when it is justified for reasons of public safety or individual well-being, this procedure can give a reasonably definitive answer. Creation of iatrogenic "cardiac cripples" can be the most common complication of screening tests and should be avoided. Therefore, good clinical judgment needs to be used in conjunction with any screening test.
Assessing Determinants of Exonic Evolutionary Rates in Mammals
Authors: F.-C. Chen, B.-Y. Liao, C.-L. Pan, H.-Y. Lin, A. Y.-F. Chang
Journal: Molecular Biology and Evolution (2012)

From studies investigating the differences in evolutionary rates between genes, gene compactness and gene expression level have been identified as important determinants of gene-level protein evolutionary rate, as represented by nonsynonymous to synonymous substitution rate (dN/dS) ratio. However, the causes of exon-level variances in dN/dS are less understood. Here, we use principal component regression to examine to what extent 13 exon features explain the variance in dN, dS, and the dN/dS ratio of human–rhesus macaque or human–mouse orthologous exons. The exon features were grouped into six functional categories: expression features, mRNA splicing features, structural–functional features, compactness features, exon duplicability, and other features, including G + C content and exon length. Although expression features are important for determining dN and dN/dS between exons of different genes, structural–functional features and splicing features explained more of the variance for exons of the same genes. Furthermore, we show that compactness features can explain only a relatively small percentage of variance in exon-level dN or dN/dS in either between-gene or within-gene comparison. By contrast, dS yielded inconsistent results in the human–mouse comparison and the human–rhesus macaque comparison. This inconsistency may suggest rapid evolutionary changes of the mutation landscape in mammals. Our results suggest that between-gene and within-gene variation in dN/dS (and dN) are driven by different evolutionary forces and that the role of mRNA splicing in causing the variation in evolutionary rates of coding sequences may be underappreciated.
Creatine supplementation as an exercise performance enhancer for patients with COPD? An idea to run with
Authors: T L Griffiths
Journal: Thorax (2005)

Creatine supplementation may enhance pulmonary rehabilitation in patients with COPD, but larger trials are needed

Multidisciplinary pulmonary rehabilitation now has an established place in the management of chronic disabling respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).1 Rehabilitation is being taken up widely on the strength of the accumulated evidence. While the effectiveness of rehabilitation is accepted, there is still considerable interest in refining and researching the individual modalities of treatment that make up the multidisciplinary intervention.

Exercise training is a key component of an effective pulmonary rehabilitation programme. In recent years a number of approaches have been taken in an effort to enhance the effectiveness of physical training, particularly for more severely disabled patients who may have reduced muscle bulk and whose baseline exercise capacity is particularly low. Broadly, strategies have either concentrated on acute interventions that enable subjects to train at higher intensity or have focused on altering underlying skeletal muscle functioning. An example of the former approach is the inclusion of oxygen supplementation during training in patients with hypoxaemia.2,3 Acute oxygen supplementation does enhance exercise performance and allows a higher work output for training. However, its use in training programmes has not been found to improve the overall outcomes of rehabilitation. Taking the alternative approach, attempts to restore muscle function have seen a crossover of techniques used for performance enhancement in sport and other areas of medicine. These interventions have included nutritional supplementation,4 the use of anabolic steroids,5 and the use of growth hormone.6 These kinds of intervention do increase muscle bulk but do not tend to produce beneficial gains in terms of whole body exercise and patient based outcomes in patients disabled by COPD and low muscle mass.

The underlying causes of …
Primary and salvage chemotherapy in advanced Hodgkin's disease: The Milan Cancer Institute experience
Authors: Gianni Bonadonna, Armando Santoro, A. Massimo Gianni, Simona Viviani, Salvatore Siena, Marco Bregni, Roberto Zucali, Fabrizio Lombardi, Valeria Bonfante, Luca Gianni, Pinuccia Valagussa
Journal: Annals of Oncology (1991)
Quantitative Genetics and Mouse Behavior
Authors: Jeanne M Wehner, Richard A Radcliffe, Barbara J Bowers
Journal: Annual Review of Neuroscience (2001)

▪ Abstract Quantitative differences are observed for most complex behavioral and pharmacological traits within any population. Both environmental and genetic influences regulate such individual differences. The mouse has proven to be a superb model in which to investigate the genetic basis for quantitative differences in complex behaviors. Genetically defined populations of mice, including inbred strains, heterogeneous stocks, and selected lines, have been used effectively to document these genetic differences. Recently, quantitative trait loci methods have been applied to map the chromosomal regions that regulate variation with the goal of eventually identifying the gene polymorphisms that reside in these regions.
Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection
Authors: Martin Holdener, Edith Hintermann, Monika Bayer, Antje Rhode, Evelyn Rodrigo, Gudrun Hintereder, Eric F. Johnson, Frank J. Gonzalez, Josef Pfeilschifter, Michael P. Manns, Matthias von G. Herrath, Urs Christen
Journal: The Journal of Experimental Medicine (2008)

Autoimmune liver diseases, such as autoimmune hepatitis (AIH) and primary biliary cirrhosis, often have severe consequences for the patient. Because of a lack of appropriate animal models, not much is known about their potential viral etiology. Infection by liver-tropic viruses is one possibility for the breakdown of self-tolerance. Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Ad-2D6-infected mice developed persistent autoimmune liver disease, apparent by cellular infiltration, hepatic fibrosis, "fused" liver lobules, and necrosis. Similar to type 2 AIH patients, Ad-2D6-infected mice generated type 1 liver kidney microsomal-like antibodies recognizing the immunodominant epitope WDPAQPPRD of cytochrome P450 2D6 (CYP2D6). Interestingly, Ad-2D6-infected wild-type FVB/N mice displayed exacerbated liver damage when compared with transgenic mice expressing the identical human CYP2D6 protein in the liver, indicating the presence of a stronger immunological tolerance in CYP2D6 mice. We demonstrate for the first time that infection with a virus expressing a natural human autoantigen breaks tolerance, resulting in a chronic form of severe, autoimmune liver damage. Our novel model system should be instrumental for studying mechanisms involved in the initiation, propagation, and precipitation of virus-induced autoimmune liver diseases.
Assaying for circulating osteopontin in practice: a technical note
Authors: D. Constantinescu, M. Vornicu, C. Grigoriu, C. Cozmei, B. D. Grigoriu
Journal: European Respiratory Journal (2010)

These data suggest that the extra sensitivity provided by AF bronchoscopy improves the ability of trainees to make the correct diagnosis at bronchoscopy and suggest a role for AFI in teaching hospitals in training inexperienced bronchoscopists.Our preliminary study shows how a ''slide bank'' of bronchoscopic images can be used to asses the diagnostic performance of a bronchoscopic system by multiple operators.We believe it is valid and eminently transferable to other studies.This work needs to be repeated with a larger sample of patients and in a population with a higher incidence of intra-epithelial neoplasia.
Anthracycline-Related Cardiomyopathy After Childhood Cancer: Role of Polymorphisms in Carbonyl Reductase Genes—A Report From the Children's Oncology Group
Authors: Javier G. Blanco, Can-Lan Sun, Wendy Landier, Lu Chen, Diego Esparza-Duran, Wendy Leisenring, Allison Mays, Debra L. Friedman, Jill P. Ginsberg, Melissa M. Hudson, Joseph P. Neglia, Kevin C. Oeffinger, A. Kim Ritchey, Doojduen Villaluna, Mary V. Relling, Smita Bhatia
Journal: Journal of Clinical Oncology (2011)

Carbonyl reductases (CBRs) catalyze reduction of anthracyclines to cardiotoxic alcohol metabolites. Polymorphisms in CBR1 and CBR3 influence synthesis of these metabolites. We examined whether single nucleotide polymorphisms in CBR1 (CBR1 1096G>A) and/or CBR3 (CBR3 V244M) modified the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors.One hundred seventy survivors with cardiomyopathy (patient cases) were compared with 317 survivors with no cardiomyopathy (controls; matched on cancer diagnosis, year of diagnosis, length of follow-up, and race/ethnicity) using conditional logistic regression techniques.A dose-dependent association was observed between cumulative anthracycline exposure and cardiomyopathy risk (0 mg/m(2): reference; 1 to 100 mg/m(2): odds ratio [OR], 1.65; 101 to 150 mg/m(2): OR, 3.85; 151 to 200 mg/m(2): OR, 3.69; 201 to 250 mg/m(2): OR, 7.23; 251 to 300 mg/m(2): OR, 23.47; > 300 mg/m(2): OR, 27.59; P(trend) < .001). Among individuals carrying the variant A allele (CBR1:GA/AA and/or CBR3:GA/AA), exposure to low- to moderate-dose anthracyclines (1 to 250 mg/m(2)) did not increase the risk of cardiomyopathy. Among individuals with CBR3 V244M homozygous G genotypes (CBR3:GG), exposure to low- to moderate-dose anthracyclines increased cardiomyopathy risk when compared with individuals with CBR3:GA/AA genotypes unexposed to anthracyclines (OR, 5.48; P = .003), as well as exposed to low- to moderate-dose anthracyclines (OR, 3.30; P = .006). High-dose anthracyclines (> 250 mg/m(2)) were associated with increased cardiomyopathy risk, irrespective of CBR genotype status.This study demonstrates increased anthracycline-related cardiomyopathy risk at doses as low as 101 to 150 mg/m(2). Homozygosis for G allele in CBR3 contributes to increased cardiomyopathy risk associated with low- to moderate-dose anthracyclines, such that there seems to be no safe dose for patients homozygous for the CBR3 V244M G allele. These results suggest a need for targeted intervention for those at increased risk of cardiomyopathy.
Mechanisms of neutrophil transmigration across the vascular endothelium in COPD
Authors: Jennie Gane, Robert Stockley
Journal: Thorax (2011)

Chronic obstructive pulmonary disease (COPD) is a common and important disease. Neutrophils have been shown to play a fundamental role in its development and progression. Understanding the mechanisms underlying the trafficking of neutrophils across the vascular endothelium into the lung could potentially allow the development of targeted biological treatments. The early stages of neutrophil tethering, adherence to and rolling on the endothelium have been determined. The later stages of diapedesis through the glycocalyx, endothelial cell (EC) layer and basement membrane, which are less well characterised, have been reviewed here. Evidence obtained from in vitro and in vivo work, concerning the implicated adhesion molecules on the neutrophil and endothelium, the mechanisms for neutrophil navigation through the EC junction (paracellular route) and evidence for transmigration through the body of an EC itself (transcellular route), is considered. The mechanisms are complex and are often disease and stimulus specific. There is evidence that a significant degree of redundancy occurs. Transmigration in the lung differs from that in other organs in that the neutrophil can exit the circulation either through the postcapillary venule in the systemic circulation or through the capillary in the pulmonary circulation. A number of factors make the mechanisms of transmigration within the lung and COPD model unique. These include physical differences between the flow through the capillary and the postcapillary venule, the modulating effect of the alveolar epithelium and other cells such as the macrophage, the presence of a 'diseased' neutrophil and indeed the presence or absence of acute, acute on chronic or chronic pulmonary disease.
Developing Countries Put Cervical Cancer Tests to the Test
Authors: L. Wang
Journal: JNCI Journal of the National Cancer Institute (2002)

Simpler and less costly screening tests exist and researchers are trying to predict how well these tests might perform in different resource settings. But the right test is only one component of an effective screening program. More important how do you ensure that all women who test positive for abnormalities will return for treatment? And if cervical cancer is found is there an ethical obligation to treat the women even when resources are limited?  (excerpt)