tbuckley/cabot-search huggingface dataset:
Computed Tomography Screening for Lung Cancer: Has It Finally Arrived? Implications of the National Lung Screening Trial
Authors: Denise R. Aberle, Fereidoun Abtin, Kathleen Brown
Journal: Journal of Clinical Oncology (2013)

The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer–specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.
Cardioprotection by hypoxia-inducible factor 1 alpha transfection in skeletal muscle is dependent on haem oxygenase activity in mice
Authors: Gabor Czibik, Julia Sagave, Vladimir Martinov, Bushra Ishaq, Marcus Sohl, Iren Sefland, Harald Carlsen, Filip Farnebo, Rune Blomhoff, Guro Valen
Journal: Cardiovascular Research (2009)

The present study investigates whether the cardioprotection achieved by gene delivery of hypoxia-inducible factor-1α (HIF-1α) depends on the downstream factor haem oxygenase (HMOX)-1. Immortalized cardiomyocytes (HL-1 cells) were transfected with HIF-1α or HMOX-1 and injured with hydrogen peroxide (H2O2), and death was evaluated by trypan blue staining. Quadriceps muscles of mice were treated with DNA for HIF-1α and HMOX-1, or sham-treated and electroporated, and 3 days later, hearts were isolated and subjected to global ischaemia and reperfusion. Some HIF-1α- and sham-treated mice received the HMOX blocker zinc deuteroporphyrin 2,4-bis-glycol (ZnBG) (n = 6–8 in each group). HL-1 cells were stimulated with bilirubin or the carbon monoxide donor CORM-2 before injury with H2O2. HL-1 cells which were transfected with HIF-1α or HMOX-1 had an increased survival to H2O2-induced injury compared with empty vector (n = 10–12 per group; P < 0.01 for both). When HMOX-1-luciferase reporter mice were treated with HIF-1α in the quadriceps muscle, increased luciferase activity was found locally, but nowhere else. Mice pre-treated with HIF-1α or HMOX-1 had a reduced infarct size, improved post-ischaemic function, and increased serum bilirubin (P < 0.05). ZnBG inhibited all these effects afforded by HIF-1α. Stimulation of HL-1 cells with bilirubin and CORM-2 reduced cell death evoked by H2O2 (P < 0.05 for both, n = 11–15 in each group). HIF-1α and HMOX-1 provided protection against H2O2-induced damage in HL-1 cells. Remote gene delivery of HIF-1α afforded cardioprotective effects. These were dependent on HMOX activity, as an HMOX blocker abolished the effects, and they were mimicked by pre-treatment with HMOX-1. Downstream to HMOX-1, bilirubin as well as carbon monoxide may be organ effectors.
Six-Year Effect of Combined Vitamin C and E Supplementation on Atherosclerotic Progression
Authors: Riitta M. Salonen, Kristiina Nyyssönen, Jari Kaikkonen, Elina Porkkala-Sarataho, Sari Voutilainen, Tiina H. Rissanen, Tomi-Pekka Tuomainen, Veli-Pekka Valkonen, Ulla Ristonmaa, Hanna-Maaria Lakka, Meri Vanharanta, Jukka T. Salonen, Henrik E. Poulsen
Journal: Circulation (2003)

Background— Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT). Methods and Results— The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol ≥5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P =0.014), in men by 33% (95% CI, 4 to 62, P =0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P =0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P =0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol. Conclusions— These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.
Effect of Breastfeeding on Lung Function in Childhood and Modulation by Maternal Asthma and Atopy
Authors: Theresa W. Guilbert, Debra A. Stern, Wayne J. Morgan, Fernando D. Martinez, Anne L. Wright
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: The protective effect of breastfeeding on early respiratory infections is well established, but its relationship to the development of subsequent asthma remains controversial.Objectives: To clarify these complex issues, we examined the association between lung function and infant-feeding practices.Methods: In the Tucson Children's Respiratory Study, feeding practices were assessed prospectively based on questionnaires completed at enrollment and well-child visits. Formula introduction was categorized as having occurred before 2 months (n = 143, "early formula introduction"), from 2 and before 4 months (n = 336), or at 4 months and older (n = 200, "longer breastfed"). Lung function was measured at age 11 and 16 years. A random-effects model was used to assess the relationship of infant-feeding practices to measures of lung function.Measurements and Main Results: FVC by age 16 was increased by 103 ± 40.0 ml (P = 0.01), and the FEV1/FVC ratio was lower (−1.9 ± 0.6%, P = 0.004) in the longer breastfed children compared with children with early formula introduction. This effect was modified after stratifying by maternal asthma. Compared with children with early formula introduction, longer breastfed children with asthmatic mothers had an FVC that was not increased (P = 0.7) and an FEV1/FVC ratio (−5.7 ± 2.4%, P = 0.02) that was significantly decreased by age 16. Longer breastfed children with nonatopic, nonasthmatic mothers demonstrated an increased FVC (142 ± 71.1 ml, P = 0.047) and no decrease in FEV1/FVC (P = 0.7) compared with children with early formula introduction.Conclusions: Longer duration of breastfeeding favorably influences lung growth in children. However, in the presence of maternal asthma, longer breastfeeding is associated with decreased airflows.
719 OBSERVATIONS OF HEPATOCELLULAR CARCINOMA (HCC) MANAGEMENT PATTERNS FROM THE GLOBAL HCC BRIDGE STUDY: SECOND INTERIM ANALYSIS OF THE EUROPEAN (EU) COHORT
Authors: F. Izzo, M. Colombo, V. Leroy, J.-F. Blanc, P. Johnson, S. Fenwick, P. Stal, E. Assenat, A. Matilla, S. Pascual Bartolome, V. Bourcier, F. Degos, B. Huang, S. Wagner, L. Orsini
Journal: Journal of Hepatology (2012)
Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity
Authors: Claude Botha, Adam D Farmer, Matias Nilsson, Christina Brock, Ana D Gavrila, Asbjørn Mohr Drewes, Charles H Knowles, Qasim Aziz
Journal: Gut (2014)

<h3>Objectives</h3> Autonomic nervous system dysfunction has been implicated in visceral hypersensitivity. However, the specific contribution of the parasympathetic nervous system (PNS) is unclear. We aimed to determine whether physiological and pharmacological manipulation of parasympathetic tone influences the development of hypersensitivity in a validated model of acid-induced oesophageal pain. <h3>Design</h3> Prior to, and following, a 30-min distal oesophageal infusion of 0.15 M hydrochloric acid, pain thresholds to electrical stimulation were determined in the proximal non-acid exposed oesophagus in healthy subjects. Validated sympathetic (skin conductance response) and parasympathetic (cardiac vagal tone) parameters were measured at baseline and continuously thereafter. In study 1, 55 subjects were randomised in a pragmatic blinded crossover design to receive deep breathing or un-paced breathing during acid infusion. In study 2, 32 subjects were randomised in a blinded, crossover design to receive intravenous atropine or placebo (saline) with deep breathing during acid infusion. <h3>Results</h3> Study 1: Deep breathing increased cardiac vagal tone (2.1±2.3 vs −0.3±2.3, p=0.0006) with concomitant withdrawal of skin conductance response (−0.6±4.9 vs 3±4.8, p=0.03) in comparison with un-paced breathing. Deep breathing prevented the development of acid-induced oesophageal hypersensitivity in comparison with sham breathing (p=0.0001). Study 2: Atropine, in comparison with placebo, blocked the attenuating effect of deep breathing on the development of acid-induced oesophageal hypersensitivity (p=0.046). <h3>Conclusions</h3> The development of oesophageal hyperalgesia is prevented by physiologically increasing parasympathetic tone. This effect is pharmacologically blocked with atropine, providing evidence that the PNS influences the development of oesophageal pain hypersensitivity.
Osteopontin deficiency dampens the pro-atherogenic effect of uraemia
Authors: Tanja X. Pedersen, Marie Madsen, Nanna Junker, Christina Christoffersen, Jonas Vikeså, Susanne Bro, Anna Hultgårdh-Nilsson, Lars Bo Nielsen
Journal: Cardiovascular Research (2013)

Uraemia is a strong risk factor for cardiovascular disease. Osteopontin (OPN) is highly expressed in aortas of uraemic apolipoprotein E knockout (E KO) mice. OPN affects key atherogenic processes, i.e. inflammation and phenotypic modulation of smooth muscle cells (SMCs). We explored the role of OPN on vascular pathology in uraemic mice. Uraemia was induced by 5/6 nephrectomy in E KO and in OPN and E double KO mice (E/OPN KO). In E KO mice, uraemia increased the relative surface plaque area in the aortic arch (from 28 ± 2% [n = 15], to 37 ± 3% [n = 20] of the aortic arch area, P < 0.05). A positive correlation was observed between plasma OPN and aortic atherosclerosis in uraemic E KO mice (r2 = 0.48, P = 0.001). In contrast, aortic atherosclerosis was not increased by uraemia in E/OPN KO mice. OPN deficiency in haematopoietic cells (including macrophages) did not affect development of uraemic atherosclerosis, even though OPN-deficient foam cells had decreased inflammatory capacity. Gene expression analyses indicated that uraemia de-differentiates SMCs in the arterial wall. This effect was dampened in whole-body OPN-deficient mice. The data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells.
Acute exacerbations in patients with COPD: predictors of need for mechanical ventilation
Authors: M. Vitacca, E. Clini, R. Porta, K. Foglio, N. Ambrosino
Journal: European Respiratory Journal (1996)

Predictive factors in mechanically-ventilated patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) have been extensively studied but not in spontaneously breathing patients. The aim of this retrospective study was to evaluate the contribution of parameters of respiratory mechanics, clinical and nutritional status in predicting the need for mechanical ventilation (MV) in COPD patients treated with medical therapy for an acute exacerbation. Anthropometric data, Acute Physiology and Chronic Health Evaluation (APACHE) II score, bedside spirometry, breathing pattern, respiratory mechanics and blood gases were measured in 39 COPD patients upon hospital admission for exacerbation of their disease. Fourteen patients in whom MV was necessary were compared with 25 patients in whom medical therapy was enough for a good outcome. The discriminant analysis showed, with decreasing order of power, that nutritional prognostic index (NPI), APACHE II score, forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio, vital capacity (VC) (% predicted) and FVC (% pred) provided a significant distinction between the two groups. The discriminant equation considering NPI, and FVC (% pred) could correctly predict the success in 76% of the patients. A multiparametric stepwise regression analysis showed that APACHE II score was significantly correlated with NPI, VC (% pred), pressure time index (PTI) and duty cycle, i.e. fraction of inspiration to duration of total breathing cycle (tl/ttot). In conclusion, underlying general conditions as assessed by malnutrition and APACHE II score were shown to be unfavourable indices of outcome for chronic obstructive pulmonary disease patients who experienced an exacerbation of their disease and were treated with medical therapy. Flow limitation data as assessed by the forced expiratory manoeuvre may provide additional information.
Prurigo pigmentosa successfully treated with minocycline
Authors: M. ASO, T. MIYAMOTO, T. MORIMURA, S. SHIMAO
Journal: British Journal of Dermatology (1989)

Five patients with prurigo pigmentosa were treated with 100-200 mg minocycline daily. The eruption and pruritus rapidly resolved within a few days or up to a week. There has been no recurrence after stopping medication and we conclude that minocycline is effective for prurigo pigmentosa and safer than dapsone.
Restricting Excessive Cardiac Action Potential and QT Prolongation
Authors: Norbert Jost, László Virág, Miklós Bitay, János Takács, Csaba Lengyel, Péter Biliczki, Zsolt Nagy, Gábor Bogáts, David A. Lathrop, Julius G. Papp, András Varró
Journal: Circulation (2005)

Background— Although pharmacological block of the slow, delayed rectifier potassium current ( I Ks ) by chromanol 293B, L-735,821, or HMR-1556 produces little effect on action potential duration (APD) in isolated rabbit and dog ventricular myocytes, the effect of I Ks block on normal human ventricular muscle APD is not known. Therefore, studies were conducted to elucidate the role of I Ks in normal human ventricular muscle and in preparations in which both repolarization reserve was attenuated and sympathetic activation was increased by exogenous dofetilide and adrenaline. Methods and Results— Preparations were obtained from undiseased organ donors. Action potentials were measured in ventricular trabeculae and papillary muscles using conventional microelectrode techniques; membrane currents were measured in ventricular myocytes using voltage-clamp techniques. Chromanol 293B (10 μmol/L), L-735,821 (100 nmol/L), and HMR-1556 (100 nmol/L and 1 μmol/L) produced a &lt;12-ms change in APD while pacing at cycle lengths ranging from 300 to 5000 ms, whereas the I Kr blockers sotalol and E-4031 markedly lengthened APD. In voltage-clamp experiments, L-735,821 and chromanol 293B each blocked I Ks in the presence of E-4031 to block I Kr . The E-4031–sensitive current ( I Kr ) at the end of a 150-ms-long test pulse to 30 mV was 32.9±6.7 pA (n=8); the L-735,821–sensitive current ( I Ks ) magnitude was 17.8±2.94 pA (n=10). During a longer 500-ms test pulse, I Kr was not substantially changed (33.6±6.1 pA; n=8), and I Ks was significantly increased (49.6±7.24 pA; n=10). On application of an “action potential–like” test pulse, I Kr increased as voltage became more negative, whereas I Ks remained small throughout all phases of the action potential–like test pulse. In experiments in which APD was first lengthened by 50 nmol/L dofetilide and sympathetic activation was increased by 1 μmol/L adrenaline, 1 μmol/L HMR-1556 significantly increased APD by 14.7±3.2% ( P &lt;0.05; n=3). Conclusions— Pharmacological I Ks block in the absence of sympathetic stimulation plays little role in increasing normal human ventricular muscle APD. However, when human ventricular muscle repolarization reserve is attenuated, I Ks plays an increasingly important role in limiting action potential prolongation.
A case of junctional epidermolysis bullosa with prurigo-like lesions and reduction of collagen XVII and filaggrin
Authors: L. Cifuentes, D. Kiritsi, W. Chen, J. Pennino, J. Ring, S. Weidinger, C. Has
Journal: British Journal of Dermatology (2013)

Funding sources: L.C. was supported by 'Kommission Klinische Forschung' (KKF) of the Technical University Munich and CK Care Foundation, and C.H. by DFG 5663/2‐1. Conflicts of interest: none declared. Madam, Junctional epidermolysis bullosa (JEB) is a group of heterogeneous, autosomal recessive genodermatoses, characterized by blister formation after minor trauma and skin cleavage within the lamina lucida.1 The main subtypes, JEB‐Herlitz and JEB‐other, are caused by mutations in the genes for the laminin 332 chains, or for the transmembrane collagen XVII (COL17A1). Additional rare subtypes are associated with mutations in the genes for the integrin subunits α6, α3 and β4. Collagen XVII is a structural component of hemidesmosomes, multiprotein complexes that mediate adhesion of keratinocytes to the underlying basement membrane. In most cases, JEB‐other is associated with null mutations leading to loss of collagen XVII, and is characterized by generalized blisters, atrophic scars and dyspigmentation, partial alopecia, dystrophic nails, mild mucosal involvement and dental anomalies. Missense or splice‐site mutations allowing residual protein expression may cause milder and/or localized phenotypes.2, 3
Clinicians sidelined about whether "exceptional" cancer drugs should be funded
Authors: A. O'Dowd
Journal: BMJ (2008)

Doctors are being sidelined in decisions about whether patients with cancer should get their requests for exceptional drugs approved when they are not available on the NHS, says a report.

A survey of England’s primary care trusts by the charity Rarer Cancers Forum found large differences in the policies and processes for approving such requests or appeals. The forum’s report, Taking Exception , calls the current situation chaotic and unfair.

Patients can lodge an “exceptional request” with their local primary care trust for drugs to be funded that are not approved for prescribing in the NHS by the national watchdog, the National Institute for Health and Clinical Excellence (NICE). Patients …
Peripheral T-Cell Lymphoma With Aberrant Expression of CD30, CD15, and CD20
Authors: Joo Y. Song, Ted Strom, Mark Raffeld, Stefania Pittaluga, Elaine S. Jaffe
Journal: Journal of Clinical Oncology (2011)

Case ReportA 72-year-old male presented with slowly growing submental and inguinal lymph nodes for the previous 3 months.A biopsy of the submental lymph node was performed, and flow cytometric analysis showed a predominant population of cells positive for CD3, CD5, dim CD7, and CD20 and negative for CD4, CD19, and surface immunoglobulin.The lymph node architecture was effaced by atypical cells of varying size arranged in cords and large sheets.These cells had irregular nuclear contours, vesicular chromatin, and occasional prominent nucleoli.Rare bizarre cells and occasional Reed-Sternberg-like cells were seen (Fig 1A).Mitotic figures were abundant.The background contained small lymphocytes and histiocytes, but no eosinophils or neutrophils were appreciated.According to immunohistochemistry, the neoplastic cells were positive for CD20 (Fig 1B), CD2 (subset), CD3 (Fig 1C), CD5, CD30 (subset; Fig 1D), CD15 (subset; Fig 1D inset), MUM1, and CD45.The cells were negative for CD79a, PAX5 (Fig 1B inset), CD4, CD8, TIA1, granzyme B, CD56, ALK1, and in situ hybridization for Epstein-Barr virus (EBV) -encoded RNA.Molecular studies for immunoglobulin gene rearrangement
Control of hyperactivation in sperm
Authors: S. S. Suarez
Journal: Human Reproduction Update (2008)

BACKGROUNDSperm hyperactivation is critical to fertilization, because it is required for penetration of the zona pellucida. Hyperactivation may also facilitate release of sperm from the oviductal storage reservoir and may propel sperm through mucus in the oviductal lumen and the matrix of the cumulus oophorus. Hyperactivation is characterized by high amplitude, asymmetrical flagellar bending.
Comparing population attributable risks for heart disease across the adult lifespan in women
Authors: Wendy J Brown, Toby Pavey, Adrian E Bauman
Journal: British Journal of Sports Medicine (2014)

Background Recent estimates suggest that high body mass index (BMI), smoking, high blood pressure (BP) and physical inactivity are leading risk factors for the overall burden of disease in Australia. The aim was to examine the population attributable risk (PAR) of heart disease for each of these risk factors, across the adult lifespan in Australian women. Methods PARs were estimated using relative risks (RRs) for each of the four risk factors, as used in the Global Burden of Disease Study, and prevalence estimates from the Australian Longitudinal Study on Women's Health, in 15 age groups from 22–27 (N=9608) to 85–90 (N=3901). Results RRs and prevalence estimates varied across the lifespan. RRs ranged from 6.15 for smoking in the younger women to 1.20 for high BMI and high BP in the older women. Prevalence of risk exposure ranged from 2% for high BP in the younger women to 79% for high BMI in mid-age women. In young adult women up to age 30, the highest population risk was attributed to smoking. From age 31 to 90, PARs were highest for physical inactivity. Conclusions From about age 30, the population risk of heart disease attributable to inactivity outweighs that of other risk factors, including high BMI. Programmes for the promotion and maintenance of physical activity deserve to be a much higher public health priority for women than they are now, across the adult lifespan.