tbuckley/cabot-search huggingface dataset:
The Role of Health Plans in Tobacco Control
Authors: Marc W. Manley, Tom Griffin, Steven S. Foldes, Carolyn C. Link, Rebecca A.J. Sechrist
Journal: Annual Review of Public Health (2003)

▪ Abstract Health plans play an important role in tobacco control. In this chapter we present an overview of the scientific research on health plan involvement in clinical and community interventions regarding tobacco use. Also included are interventions that have been undertaken by health plans to lower smoking rates among their members and the general population. We conclude with a new model that can be used to engage health plans in tobacco control efforts and a case study that outlines how one health plan has implemented this new model.
UK immigrant screening is inversely related to regional tuberculosis burden
Authors: M. Pareek, I. Abubakar, P. J. White, G. P. Garnett, A. Lalvani
Journal: Thorax (2011)

been described by other authors as the 'reversed halo sign'.Zompatori et al 2 first used the term 'atoll sign' in 1999 to describe the imaging finding of a focal rounded area of ground-glass opacity surrounded by a more or less complete ring of consolidation. 3 Although the abnormality frequently resembles an atoll, the Fleischner Society 4 prefers the term 'reversed halo sign', as initially proposed by Kim et al. 3 Although both terms adequately describe the imaging characteristics of the lesion, the term 'reversed halo sign' should be used to avoid confusion and to standardise the keywords used in literature searches.A review of the US National Institutes of Health digital archive of biomedical and life sciences journal literature (PubMed) found only three occurrences of the term 'atoll sign', whereas the term 'reversed halo sign' was found in 22 articles.The uniform use of descriptors is critical when reporting on lesions, to avoid the overlooking of otherwise important articles, such as the one presented by Walsh and Robertson, in literature reviews.
Association Between Germline HOXB13 G84E Mutation and Risk of Prostate Cancer
Authors: M. R. Akbari, J. Trachtenberg, J. Lee, S. Tam, R. Bristow, A. Loblaw, S. A. Narod, R. K. Nam
Journal: JNCI Journal of the National Cancer Institute (2012)

Recently, a G84E mutation in HOXB13 , a gene involved in prostate development, was shown to be strongly associated with an increased risk of prostate cancer. To confirm this association in a screening setting, we conducted a case–control study and sequenced germline DNA from peripheral leukocytes of 1843 men diagnosed with prostate cancer (case subjects) and 2225 men without prostate cancer (control subjects) for mutations in HOXB13 . Subjects (aged 40–94 years) were prescreened and underwent a prostate biopsy at two tertiary care centers in Canada. The frequency of HOXB13 variants was determined in case subjects and control subjects by race, and odds ratios and 95% confidence intervals were based on 2×2 table analysis. All statistical tests were two-sided. Twelve men of white race were identified to be carriers of the G84E mutation. The G84E mutation was more frequent among white case subjects than among white control subjects (10 of 1525 [0.7%] vs 2 of 1757 [0.1%], P = .01) and was associated with an increased risk of prostate cancer (unadjusted odds ratio = 5.8, 95% confidence interval = 1.3 to 26.5, P = .01).
Diagnosis and Treatment of Early Melanoma
Authors: Lowell A. Goldsmith
Journal: JAMA (1992)

THE INCIDENCE of melanoma of the skin appears to be rapidly rising. The increased incidence may be partially attributable to increased detection resulting from screening. In 1992, approximately 32000 newly diagnosed cases and 6700 deaths are expected in the United States. Melanoma tends to occur in adults in the prime of their family and professional lives. Detection and surgical treatment of the early stages of this malignancy are usually curative. In contrast, diagnosis and treatment in late stages often have dismal results. Traits associated with an increased risk of developing melanoma include multiple typical moles, atypical moles, freckling, history of severe sunburn, ease of burning, inability to tan, and light hair with blue eyes. Other factors include the presence of familial atypical mole and melanoma syndrome, disorders of DNA repair, and excessive sun exposure. Efforts to increase public awareness of melanoma and its treatment without causing unnecessary fear present a
Radiosensitization of Epidermal Growth Factor Receptor/HER2–Positive Pancreatic Cancer Is Mediated by Inhibition of Akt Independent of Ras Mutational Status
Authors: Randall J. Kimple, Angelina V. Vaseva, Adrienne D. Cox, Kathryn M. Baerman, Benjamin F. Calvo, Joel E. Tepper, Janiel M. Shields, Carolyn I. Sartor
Journal: Clinical Cancer Research (2010)

Epidermal growth factor receptor (EGFR) family members (e.g., EGFR, HER2, HER3, and HER4) are commonly overexpressed in pancreatic cancer. We investigated the effects of inhibition of EGFR/HER2 signaling on pancreatic cancer to elucidate the role(s) of EGFR/HER2 in radiosensitization and to provide evidence in support of further clinical investigations.Expression of EGFR family members in pancreatic cancer lines was assessed by quantitative reverse transcription-PCR. Cell growth inhibition was determined by MTS assay. The effects of inhibition of EGFR family receptors and downstream signaling pathways on in vitro radiosensitivity were evaluated using clonogenic assays. Growth delay was used to evaluate the effects of nelfinavir on in vivo tumor radiosensitivity.Lapatinib inhibited cell growth in four pancreatic cancer cell lines, but radiosensitized only wild-type K-ras-expressing T3M4 cells. Akt activation was blocked in a wild-type K-ras cell line, whereas constitutive phosphorylation of Akt and extracellular signal-regulated kinase (ERK) was seen in lines expressing mutant K-ras. Overexpression of constitutively active K-ras (G12V) abrogated lapatinib-mediated inhibition of both Akt phosphorylation and radiosensitization. Inhibition of MAP/ERK kinase/ERK signaling with U0126 had no effect on radiosensitization, whereas inhibition of activated Akt with LY294002 (enhancement ratio, 1.2-1.8) or nelfinavir (enhancement ratio, 1.2-1.4) radiosensitized cells regardless of K-ras mutation status. Oral nelfinavir administration to mice bearing mutant K-ras-containing Capan-2 xenografts resulted in a greater than additive increase in radiation-mediated tumor growth delay (synergy assessment ratio of 1.5).Inhibition of EGFR/HER2 enhances radiosensitivity in wild-type K-ras pancreatic cancer. Nelfinavir, and other phosphoinositide 3-kinase/Akt inhibitors, are effective pancreatic radiosensitizers regardless of K-ras mutation status.
Chronic Dyspnea, Ascites, and Muffled Heart Sounds
Authors: Ali Alizadeh
Journal: JAMA (1976)

History  An 18-year-old woman had a history of increasing abdominal enlargement and dyspnea of five years' duration. There was mild cyanosis, distended neck veins, muffled heart sounds, abdominal dullness, and liver enlargement on physical examination. Posteroanterior and lateral chest roentgenograms were taken.  Diagnosis  Constrictive pericarditis with pericardial calcification.  Figure 1 shows moderate cardiac enlargement and a calcified plaque along the left contour just below the pulmonary artery. Figure 2 shows a calcific ring almost completely encircling the heart.  The cause of constrictive pericarditis remains in doubt in many patients. 1 In some cases, there is a high percentage of tuberculous origin. In other series, tuberculosis has been an infrequent cause. The disorder may also occur following pyogenic infections, connective tissue and neoplastic disease, trauma, radiation, histoplasmosis, active viral infection, asbestosis, and chronic renal failure with uremia.  In nearly 50% of patients with constrictive pericarditis, pericardial calcifications can be demonstrated roentgenographically.
Howling for the moon
Authors: N. Barnes, A. Bush
Journal: Thorax (2011)

Rennard and Vestbo have sounded a ringing call to arms.1 Instead of trying to make minor improvements in the rate of decline of spirometry in patients with chronic obstructive pulmonary disease (COPD), they call for an all out effort to find a cure. Their arguments have attractions, but we believe that the evidence shows it would be easier to hatch out chickens from a plate of scrambled eggs than to cure COPD in adults.

COPD is defined for epidemiological and most clinical purposes by spirometry. When the underlying pathological changes cause spirometric measures to cross over a given threshold COPD is diagnosed. However, the crossing of this threshold depends on two factors, first the peak lung function attained as a young adult and secondly the deterioration with ageing accelerated by smoking and probably other environmental exposures.

First, some notes of caution. Spirometers are dangerous instruments in many contexts, not least public health. Extensive distal airway obstruction will not be detected by spirometry, and ‘a normal’ first second forced expired volume (FEV1) is very far from being reassuring that all is well. By the time the potential patient with COPD has lost FEV1, extensive and irreparable lung destruction will be present. Although well performed spirometry has a high reproducibility, extensive distal airway obstruction can occur before it is detected. Furthermore, the normal range of spirometry is very wide and so an individual who starts off with very good lung function can still be in the normal range, but for them it is a major loss of lung function.

Peak lung function is reached at 16–18 years in females and 20–25 years in males.2 3 The height of that plateau depends on two factors: the starting point for airway function immediately after birth, and the rate of growth between …
Propranolol for the prevention of first esophageal variceal hemorrhage: A lifetime commitment?
Authors: Diane R. Abraczinskas, Rie Ookubo, Norman D. Grace, Roberto J. Groszmann, Jaime Bosch, Guadalupe Garcia-Tsao, Caroline R. Richardson, Daniel S. Matloff, Juan Rodés, Harold O. Conn
Journal: Hepatology (2001)

Although β blockers have had significant impact in the treatment of portal hypertension, the question of how long they should be continued for prevention of variceal hemorrhage remains unknown. Prospective studies on β blockers to prevent variceal hemorrhage lack long-term follow-up, and indefinite administration of β blockers for primary prevention of variceal bleeding has become standard practice. The aim of this study was to determine the outcomes of patients in whom β blocker therapy was discontinued. Patients completing a prospective, randomized, double-blind, placebo-controlled trial of propranolol for the primary prevention of variceal hemorrhage were tapered off of propranolol and placebo and followed prospectively for subsequent events. Of the 49 patients in the follow-up study (25 former propranolol, 24 former placebo), 9 experienced variceal hemorrhage (6 former propranolol, 3 former placebo). Following withdrawal of propranolol, the freedom from variceal bleeding was not significantly different between these 2 groups of patients, suggesting that the protective effect of propranolol against variceal hemorrhage, noted previously, was no longer present. Seventeen patients died (12 former propranolol, 5 former placebo) during the follow-up study. Cumulative survival was longer in the placebo group. These trends for EVH and survival were opposite to those observed in the original study population while patients were taking medication. When propranolol is withdrawn, the risk of variceal hemorrhage returns to what would be expected in an untreated population. Patients who discontinue β blockers experience increased mortality compared with an untreated population. These observations support the current practice of indefinite prophylactic therapy.
First TV advertisement for e-cigarettes prompts complaints
Authors: A. O'Dowd
Journal: BMJ (2014)

The first television advertisements in the United Kingdom to promote electronic (e) cigarettes have prompted complaints to the Advertising Standards Authority.

The BMA said that the commercials for VIP e-cigarettes, first shown on 10 November, breached guidelines by glamorising so called “vaping”—the act of using an e-cigarette—and by targeting children. The association has written to the Advertising Standards Authority saying that the …
Growth Factors in the Collateral Circulation of Chronic Total Coronary Occlusions
Authors: Gerald S. Werner, Enrico Jandt, Andreas Krack, Gero Schwarz, Oliver Mutschke, Friedhelm Kuethe, Markus Ferrari, Hans R. Figulla
Journal: Circulation (2004)

Background— Despite extensive animal experimental evidence, there are few data on the relation of growth factors and collateral function in humans. Methods and Results— In 104 patients with a chronic total coronary occlusion (CTO; &gt;2 weeks’ duration), collateral function was assessed invasively during recanalization by intracoronary Doppler and pressure recordings. A collateral resistance index, R Coll , was calculated. Blood samples were drawn from the distal coronary bed supplied by the collaterals and from the aortic root to measure basic fibroblast growth factor (bFGF), monocytic chemotactic protein-1 (MCP-1), transforming growth factor-β (TGF-β), placenta growth factor (PlGF), and tumor necrosis factor-α (TNF-α). The bFGF concentration in the collateralized artery was higher than in the aortic root (34±20 versus 18±14 pg/mL; P &lt;0.001). bFGF was highest in recent occlusions (2 to 12 weeks) with the highest R Coll . Higher collateral concentrations were also observed for MCP-1, TGF-β, and PlGF, but without a close relation to the duration of occlusion. TNF-α was not increased in collaterals compared with the systemic circulation. MCP-1, PlGF, and TGF-β were significantly increased in small collaterals with the highest shear stress. Diabetic patients had lower bFGF and higher MCP-1 levels than nondiabetics. Conclusions— In CTOs, the continuous release of bFGF into collaterals showed a close relation to the duration of occlusion and collateral function, which underscores its therapeutic potential. Other factors influencing growth factor release appeared to be shear stress for MCP-1, TGF-β, and PlGF and the presence of diabetes.
Neural drive to the diaphragm in patients with severe COPD.
Authors: A De Troyer, J B Leeper, D K McKenzie, S C Gandevia
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Patients with severe chronic obstructive pulmonary disease (COPD) have a greater neural drive to the parasternal intercostal and scalene muscles and greater inspiratory expansion of the rib cage than do healthy individuals. However, such patients also have a reduced outward displacement or a paradoxical inward displacement of the ventral abdominal wall during inspiration. This has led to the suggestion that they may have less use of the diaphragm, possibly secondary to chronic muscle fatigue. To assess the effect of COPD on the neural drive to the diaphragm, we inserted needle electrodes into the costal part of the right hemidiaphragm in eight patients with severe disease (mean [+/- SD] FEV1: 0.82 [+/- 0.27] L) and six control subjects of similar age, and measured the discharge frequencies of single motor units during resting breathing. A total of 115 diaphragmatic motor units were recorded in the control subjects and 122 in the patients. All motor units discharged rhythmically in phase with inspiration. However, whereas 95% of the units in the control subjects had a peak discharge frequency between 7 and 14 Hz, 79% of the units in the COPD patients had a peak discharge frequency greater than 15 Hz. As a result, the discharge frequency of all units averaged 10.5 [+/- 2.4] Hz in the control subjects, but 17.9 [+/- 4.3] Hz in the patients (p < 0.001). These observations indicate that patients with severe COPD have an increased neural drive not only to the rib cage inspiratory muscles, but also to the diaphragm. Consequently, the reduced inspiratory expansion of the abdomen in severe COPD results from mechanical factors alone.
Pathogenic virus-specific T cells cause disease during treatment with the calcineurin inhibitor FK506: implications for transplantation
Authors: Koichi Araki, Shivaprakash Gangappa, Dirck L. Dillehay, Barry T. Rouse, Christian P. Larsen, Rafi Ahmed
Journal: The Journal of Experimental Medicine (2010)

Recently, several cases of fatal lymphocytic choriomeningitis virus (LCMV) infection occurred in transplant recipients being treated with the immunosuppressive calcineurin inhibitor FK506. These findings were surprising because LCMV is a noncytolytic virus. To understand how a noncytolytic virus can cause disease under conditions of immunosuppression, we used the mouse LCMV model and found that, similar to the observations in human transplant recipients, LCMV infection of FK506-treated mice resulted in a lethal disease characterized by viremia, lack of seroconversion, and minimal lymphocytic infiltrates in the tissues. However, despite the apparent absence of an antiviral immune response, this disease was orchestrated by virus-specific T cells. FK506 did not prevent the generation and proliferation of LCMV-specific T cells but instead altered their differentiation so that these effector T cells lost the ability to control virus but were still capable of mediating disease. These pathogenic T cells initiated a cytokine storm characterized by high levels of tumor necrosis factor (TNF) and interleukin 6 (IL-6), and depletion of T cells or blockade of these inflammatory cytokines prevented the lethal disease. Our study shows that inhibiting calcineurin can generate pathogenic T cells and indicates that T cell–mediated viral disease can occur even under conditions of immunosuppression. Furthermore, we identify a potential strategy (blockade of TNF and IL-6) for treatment of transplant recipients who have acute complications of viral infection.
Validation of a Molecular and Pathological Model for Five-Year Mortality Risk in Patients with Early Stage Lung Adenocarcinoma
Authors: Raphael Bueno, Elisha Hughes, Susanne Wagner, Alexander S. Gutin, Jerry S. Lanchbury, Yifan Zheng, Michael A. Archer, Corinne Gustafson, Joshua T. Jones, Kristen Rushton, Jennifer Saam, Edward Kim, Massimo Barberis, Ignacio Wistuba, Richard J. Wenstrup, William A. Wallace, Anne-Renee Hartman, David J. Harrison
Journal: Journal of Thoracic Oncology (2014)

The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality.Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome.The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12-1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10).This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality.
Sex ratio following preconception low-dose aspirin in women with prior pregnancy loss
Authors: Rose G. Radin, Sunni L. Mumford, Robert M. Silver, Laurie L. Lesher, Noya Galai, David Faraggi, Jean Wactawski-Wende, Janet M. Townsend, Anne M. Lynch, Hyagriv N. Simhan, Lindsey A. Sjaarda, Neil J. Perkins, Shvetha M. Zarek, Karen C. Schliep, Enrique F. Schisterman
Journal: Journal of Clinical Investigation (2015)

Several lines of evidence suggest that male embryos may have greater vulnerability than female embryos to disordered inflammation; therefore, antiinflammatory drugs, such as low-dose aspirin (LDA), may alter the sex ratio. Here, we assessed the effect of LDA on male live birth and male offspring, incorporating pregnancy losses (n = 56) via genetic assessment, as part of a parallel-design, block-randomized, placebo-controlled trial of preconception LDA.Participants (615 treated with LDA, 613 treated with placebo) ranged in age from 18 to 40 years of age, with 1 to 2 prior pregnancy losses. We estimated the intention-to-treat (ITT) risk ratio (RR) and 95% CI and assessed interaction with baseline high-sensitivity C-reactive protein (hsCRP) serum concentration - a marker of systemic inflammation.Among the 1,078 women who completed follow-up (535 treated with LDA, 543 treated with placebo), the male live birth ITT RR equaled 1.31 (95% CI: 1.07-1.59). With increasing tertile of hsCRP, the proportion of males at birth decreased in the placebo group, and the effect of LDA on male live birth increased (first tertile: 48% male in LDA vs. 52% in placebo, ITT RR = 0.97, 95% CI: 0.70-1.35; second tertile: 57% male in LDA vs. 43% in placebo, ITT RR = 1.36, 95% CI: 0.98-1.90; third tertile: 53% male in LDA vs. 35% in placebo, ITT RR = 1.70, 95% CI: 1.13-2.57; P interaction = 0.03). Analysis of pregnancy with male offspring yielded similar results.Initiation of LDA prior to conception restored numbers of male live births and pregnancy with male offspring among women with 1 to 2 prior pregnancy losses. Moreover, our data suggest that LDA modulates inflammation that would otherwise reduce the conception or survival of male embryos.ClinicalTrials.gov NCT00467363.Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.