tbuckley/cabot-search huggingface dataset:
Use of the Land Snail <i>Helix aspersa</i> as Sentinel Organism for Monitoring Ecotoxicologic Effects of Urban Pollution: An Integrated Approach
Authors: Francesco Regoli, Stefania Gorbi, Daniele Fattorini, Sara Tedesco, Alessandra Notti, Nicola Machella, Raffaella Bocchetti, Maura Benedetti, Francesco Piva
Journal: Environmental Health Perspectives (2005)

Atmospheric pollution from vehicular traffic is a matter of growing interest, often leading to temporary restrictions in urban areas. Although guidelines indicate limits for several parameters, the real toxicologic impacts remain largely unexplored in field conditions. In this study our aim was to validate an ecotoxicologic approach to evaluate both bioaccumulation and toxicologic effects caused by airborne pollutants. Specimens of the land snail Helix aspersa were caged in five sites in the urban area of Ancona, Italy. After 4 weeks, trace metals (cadmium, chromium, copper, iron, manganese, nickel, lead, and zinc) and polycyclic aromatic hydrocarbons (PAHs) were measured and these data integrated with the analyses of molecular and biochemical responses. Such biomarkers reflected the induction of detoxification pathways or the onset of cellular toxicity caused by pollutants. Biomarkers that correlated with contaminant accumulation included levels of metallothioneins, activity of biotransformation enzymes (ethoxyresorufin O-deethylase, ethoxycoumarin O-deethylase), and peroxisomal proliferation. More general responses were investigated as oxidative stress variations, including efficiency of antioxidant defenses (catalase, glutathione reductase, glutathione S-transferases, glutathione peroxidases, and total glutathione) and total oxyradical scavenging capacity toward peroxyl and hydroxyl radicals, onset of cellular damages (i.e., lysosomal destabilization), and loss of DNA integrity. Results revealed a marked accumulation of metals and PAHs in digestive tissues of organisms maintained in more traffic-congested sites. The contemporary appearance of several alterations confirmed the cellular reactivity of these chemicals with toxicologic effects of potential concern for human health. The overall results of this exploratory study suggest the utility of H. aspersa as a sentinel organism for biomonitoring the biologic impact of atmospheric pollution in urban areas.
Postcastrational Adrenal Tumors in Two Strains of Mice: Morphologic, Histochemical, and Chromatographic Studies&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A S Murthy, M A Brezak, A G Baez
Journal: JNCI Journal of the National Cancer Institute (1970)
Uptake and Utilization of Exogenous Cystine by Cystinotic and Normal Fibroblasts
Authors: Beatrice States, Dorothy Harris, Stanton Segal
Journal: Journal of Clinical Investigation (1974)

The uptake of l-[35S]cystine was studied in six cystinotic and six normal fibroblast lines grown for five days either on cover slips or in 32-oz plastic flasks. Cystinotics showed greater uptake than normals. The apparent Kt for cystine entry in both types of cells was 0.043 mM but cystinotic cells showed a higher maximum velocity of entry. A comparison of the fate of l-[35S]cystine incubated for 20 min with monolayers of cells showed 30% and 15% of the intracellular 35S to be l-cystine in cystinotic and normal cells, respectively. The 35S effluxed more slowly from cystinotic than from normal cells after a 20-min preloading with l-[35S]cystine. Identification of 35S compounds in efflux media after 3 min showed 75% of the total 35S was l-cystine with the remainder in cysteine and acidic sulfur metabolites of cystine with no essential difference between cystinotics and normals. In paired experiments, the specific activity of the effluxed l-[35S]cystine after both efflux periods was the same as that entering the cell, thus indicating that the free l-[35S]cystine had not exchanged with the pre-existing pool in the cystinotic cells. During 3 min efflux, the l-cystine pool in normal cells was depleted mainly by loss of free cystine. In cystinotic cells, a new steady state was attained after 21 min of efflux and the intracellular l-[35S]cystine had the same percentage of total radioactivity seen after the initial 20-min uptake. After the rapid efflux of l-[35S]cystine from normals, [35S]cysteine and other labeled cystine metabolites appeared in the efflux media. By the end of a 3-min efflux, cystinotic cells had incorporated more label into reduced glutathione than had normal cells. However, when the new steady state was attained in cystinotics, the amounts of 35S in glutathione were not markedly different in the two types of cells. Approximately 95% of the total label could be accounted for in free sulfur compounds.
Heme Oxygenase-1 Induction Attenuates Inducible Nitric Oxide Synthase Expression and Proteinuria in Glomerulonephritis
Authors: PRASUN K. DATTA, SEVASTI B. KOUKOURITAKI, KATHLEEN A. HOPP, ELIAS A. LIANOS
Journal: Journal of the American Society of Nephrology (1999)

In glomerulonephritis, there is intraglomerular activation of inducible nitric oxide synthase (iNOS) leading to high output production of nitric oxide (NO). This can result in supraphysiologic amounts of NO and cause oxidative injury. It is unknown whether mechanisms of cellular defense against NO-mediated injury exist. Induction of the heme catabolizing enzyme heme oxygenase-1 (HO-1), which generates biliverdin, carbon monoxide (CO), and iron (Fe), may provide such a mechanism, as CO and Fe are two negative modulators of iNOS activity and expression. This study assessed whether upregulation of HO-1 by a specific inducer, hemin, negatively modulates iNOS expression and activity in anti-glomerular basement membrane antibody-mediated glomerulonephritis. Glomerular HO-1 expression in nephritic animals was upregulated by treatment with hemin (30 micromol/kg body wt). iNOS and HO-1 mRNA expression were assessed by reverse transcription-PCR of glomerular total RNA from nephritic animals or nephritic animals pretreated with hemin. iNOS activity in glomeruli was measured by assessing conversion of [14C] L-arginine to [14C] L-citrulline. HO-1 protein levels in glomeruli were assessed by Western blot analysis. The effect of hemin treatment on monocyte/macrophage infiltration was assessed by enumeration of ED-1-positive cells in nephritic glomeruli. iNOS and HO-1 were coinduced in nephritic glomeruli. Hemin treatment of nephritic animals resulted in upregulation of glomerular HO-1 levels and a two- to threefold reduction in glomerular iNOS mRNA levels. iNOS activity in glomeruli was significantly reduced in hemin-treated nephritic animals in which proteinuria was also attenuated without a change in monocyte/macrophage infiltration. Hemin (100 to 200 microM) also reduced iNOS protein levels and enzyme activity in cultured mesangial cells stimulated with cytokines. These studies demonstrate that in glomerular immune injury, hemin treatment upregulates glomerular HO-1 with an attendant downregulation of iNOS expression, and thus points to regulatory interaction between the two systems. The beneficial effect of hemin treatment on proteinuria could be linked to downregulation of iNOS.
Heart Valve Involvement (Libman-Sacks Endocarditis) in the Antiphospholipid Syndrome
Authors: Maja Hojnik, Jacob George, Lea Ziporen, Yehuda Shoenfeld
Journal: Circulation (1996)

Abstract The antiphospholipid syndrome (APS) is defined by the presence of anti-phospholipid antibodies (aPLs) and venous or arterial thrombosis, recurrent pregnancy loss, or thrombocytopenia. The syndrome can be either primary or secondary to an underlying condition, most commonly systemic lupus erythematosus (SLE). Echocardiographic studies have disclosed heart valve abnormalities in about a third of patients with primary APS. SLE patients with aPLs have a higher prevalence of valvular involvement than those without these antibodies. Valvular lesions associated with aPLs occur as valve masses (nonbacterial vegetations) or thickening. These two morphological alterations can be combined and are thought to reflect the same pathological process. Both can be associated with valve dysfunction, although such association is much more common with the latter alteration. The predominant functional abnormality is regurgitation; stenosis is rare. The mitral valve is mainly affected, followed by the aortic valve. Valvular involvement usually does not cause clinical valvular heart disease. The presence of aPLs seems to further increase the risk for thromboembolic complications, mainly cerebrovascular, posed by valve lesions. Superadded bacterial endocarditis is rare but may be difficult to distinguish from pseudoinfective endocarditis. The current therapeutic guidelines are those for APS in general. Secondary antithrombotic prevention with long-term, high-intensity oral anticoagulation is advised. The efficacy of aspirin, either alone or in combination, is yet to be assessed. Corticosteroids are not beneficial and may even facilitate valve damage. Immunosuppressive agents should only be used for the treatment of an underlying condition. Current data suggest a role for aPLs in the pathogenesis of valvular lesions. aPLs may promote the formation of valve thrombi. These antibodies may also act by another mechanism, as indicated by the finding of subendothelial deposits of immunoglobulins, including anti-cardiolipin antibodies, and of colocalized complement components in deformed valves from patients with APS.
How to Resolve an Ethical Dilemma Concerning Randomized Clinical Trials
Authors: D Marquis
Journal: New England Journal of Medicine (1999)

An apparent ethical dilemma arises when physicians consider enrolling their patients in randomized clinical trials. Suppose that a randomized clinical trial comparing two treatments is in progress, and a physician has an opinion about which treatment is better. The physician has a duty to promote the patient's best medical interests and therefore seems to be obliged to advise the patient to receive the treatment that the physician prefers. This duty creates a barrier to the enrollment of patients in randomized clinical trials.110 Two strategies are often used to resolve the dilemma in favor of enrolling patients in clinical trials. . . .
Center of Cancer Systems Biology Second Annual Workshop—Tumor Metronomics: Timing and Dose Level Dynamics
Authors: Philip Hahnfeldt, Lynn Hlatky, Giannoula Lakka Klement
Journal: Cancer Research (2013)

Metronomic chemotherapy, the delivery of doses in a low, regular manner so as to avoid toxic side effects, was introduced over 12 years ago in the face of substantial clinical and preclinical evidence supporting its tumor-suppressive capability. It constituted a marked departure from the classic maximum-tolerated dose (MTD) strategy, which, given its goal of rapid eradication, uses dosing sufficiently intense to require rest periods between cycles to limit toxicity. Even so, upfront tumor eradication is frequently not achieved with MTD, whereupon a de facto goal of longer-term tumor control is often pursued. As metronomic dosing has shown tumor control capability, even for cancers that have become resistant to the same drug delivered under MTD, the question arises whether it may be a preferable alternative dosing approach from the outset. To date, however, our knowledge of the coupled dynamics underlying metronomic dosing is neither sufficiently well developed nor widely enough disseminated to establish its actual potential. Meeting organizers thus felt the time was right, armed with new quantitative approaches, to call a workshop on "Tumor Metronomics: Timing and Dose Level Dynamics" to explore prospects for gaining a deeper, systems-level appreciation of the metronomics concept. The workshop proved to be a forum in which experts from the clinical, biologic, mathematical, and computational realms could work together to clarify the principles and underpinnings of metronomics. Among other things, the need for significant shifts in thinking regarding endpoints to be used as clinical standards of therapeutic progress was recognized.
Effect of pirfenidone on chronic interstitial pneumonia
Authors: Hiroyuki Takoi, Yukiko Miura, Yoshiya Tsunoda, Yuki Sumazaki, Toru Tanaka, Shih-Yuan Lin, Yohei Yatagai, Akimasa Sekine, Kenji Hayashihara, Takefumi Saito
Journal: European Respiratory Journal (2012)

Background: Several reports reveal the favorable effect of pirfenidone on early stage of idiopathic pulmonary fibrosis (IPF), but impacts on non-specific interstitial pneumonia (NSIP) and interstitial pneumonia (IP) associated with collagen vascular diseases (IP-CVD) are not clear.

Objectives: To examine the effect of pirfenidone on chronic IP including IPF, NSIP and IP-CVD.

Methods: Thirty-two patients were enrolled in the study evaluating the safety and efficacy of pirfenidone in IPF, NSIP and IP-CVD. Clinical diagnosis are IPF(14), NSIP(14), IP associated with scleroderma(3), and rheumatoid arthritis(1). Based on PaO2 at rest and SpO2 after 6 minutes walk test (6MWT), disease severity of those were classified into four groups [Table 1]. We retrospectively analyzed subjective symptom in British Medical Research Council scale, pulmonary function, KL-6, SP-D and CT findings before and during pirfenidone administration.

View this table:

Table 1. Disease severity of patients





Results: Correlations was observed between subjective symptom and VC, but was not between subjective symptom and KL-6, SP-D, CT findings. After administration of pirfenidone, VC improved above 5% in 22%, 50%, 25%, 45% of patients (severity grade I, II, III, IV, respectively). Subjective symptoms highly improved in patients with scleroderma (improvement ratio: 67% in scleroderma vs. 14%, 14%, 0% in IPF, NSIP, RA, respectively).

Conclusions: Pirfenidone might have the favorable efficacy independent of disease severity, without severe adverse events, in chronic IP, especially in IP associated with scleroderma.
Lung Clearance Index and HRCT are complementary markers of lung abnormalities in young children with CF
Authors: C. M. Owens, P. Aurora, S. Stanojevic, A. Bush, A. Wade, C. Oliver, A. Calder, J. Price, S. B. Carr, A. Shankar, J. Stocks
Journal: Thorax (2011)

<h3>Rationale</h3> High resolution computed tomography (HRCT) is a more sensitive tool for detecting early cystic fibrosis (CF) lung disease than either spirometry or plain radiography, but its relationship to other measures of lung function has not been established in young children. <h3>Objectives</h3> 1) To assess whether the lung clearance index (LCI) derived from multiple breath inert-gas washout (MBW) is as effective as HRCT in identifying pulmonary abnormalities; and 2) explore the relationships between abnormalities detected by HRCT and by spirometry, plethysmography and MBW (collectively, LFTs) in young children with CF. <h3>Methods</h3> Children with CF underwent LFTs and volumetric HRCT on the same day. Healthy age-matched controls underwent identical LFTs without HRCT. Scans were anonymised, and scored using the Brody-II CT scoring system, to assess for presence and extent of bronchiectasis, airway wall thickening, mucus plugging, and parenchymal opacities. <h3>Results</h3> Assessments were undertaken in 60 children with CF (mean (SD) 7.8 (1.3) years) and 54 healthy controls (7.9 (1.2) y). Among children with CF, 84% (47/56) had abnormal LCI, 58% (27/47) abnormal plethysmographic lung volumes (FRC<sub>pleth</sub> or RV), 35% (21/60) abnormal sRaw and 47% (28/60) abnormal spirometry (FEV<sub>1</sub> or FEF<sub>25–75</sub>); whereas HRCT scans were abnormal in 85% (51/60): median total Brody-II score: 9.5% (range 0–51%). Total CT score correlated more strongly with LCI (Spearman correlation=0.77) than with spirometry (R=−0.43) or any other marker of lung function. Of the nine children with normal LCI, five had abnormalities on HRCT, whereas five children with normal HRCT had raised LCI. <h3>Conclusions</h3> These results suggest that while LCI and HRCT have similar sensitivity to detect CF lung disease, complimentary information may be gained in individual patients.
Does tube size and positioning matter in the management of spontaneous pneumothorax
Authors: Muhammad Badar Ganaie, Shiva Bikmalla, Muhammad Amin Afridi, Masood Khalil, Imran Hussain, Mohammed Haris
Journal: European Respiratory Journal (2014)

Introduction: No large RCTs compare different treatment strategies in management of primary(PSP) and secondary spontaneous pneumothorax(SSP). We aimed to review efficacy of small bore(12-18 Fr.) intercostal tube(ICT) via Seldinger technique versus large bore 9surgical9 ICT via blunt dissection. We also compared outcome measures between apical and basal ICT.  Methods: Retrospective observational study of 212 consecutive pneumothorax episodes between January and December 2012. Iatrogenic and traumatic pneumothorax were excluded. Patient case notes and plain chest radiographs were reviewed. P value of   Results: Of the 212 episodes, 51(33%) had PSP and 30(19%) SSP. 46 patients had small bore ICT and 13 large bore ICT. 16 patients had apical ICT and 23 basal. There was no statistical difference in terms of demographic data and type and size of pneumothorax in either group. Large bore ICT group had significantly higher length of stay(LOS) compared to small bore ICT (16 days versus 8.5 days; p=0.04). However, non-significant lower success rate, longer duration of ICT and comparable rate of complications and recurrence was observed in large bore ICT (p>0.05). Regarding ICT placement site, no significant difference was observed in outcomes between apical and basal ICT (p>0.05).  Conclusion: Our data has shown that small bore ICT perform better and basal ICT were as effective as apical in management of SP. RCT evidence in this field is limited and total sample size is too small to make any firm conclusions.
Baseline Findings of the Italian Multicenter Randomized Controlled Trial of "Once-Only Sigmoidoscopy"--SCORE
Authors: Nereo Segnan, Carlo Senore, Bruno Andreoni, Hugo Aste, Luigina Bonelli, Cristiano Crosta, Roberto Ferraris, Stefano Gasperoni, Angelo Penna, Mauro Risio, Francesco Paolo Rossini, Stefania Sciallero, Marco Zappa, Wendy S. Atkin
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: A single sigmoidoscopy examination at around age 60 years has been proposed as a cost-effective strategy to prevent colorectal cancer. A multicenter randomized controlled trial, the SCORE trial, is in progress in Italy to estimate the impact of this strategy on colorectal cancer incidence and mortality and the duration of the protective effect. We present the baseline screening outcomes. Methods: A questionnaire was mailed to a random sample of 236 568 people aged 55–64 years to assess their eligibility for and interest in screening. Those reporting a history of colorectal cancer, adenomas, inflammatory bowel disease, recent colorectal endoscopy, or two first-degree relatives with colorectal cancer were excluded. Eligible, interested respondents were assigned randomly to the control group (no further contact) or the intervention group (invitation to undergo sigmoidoscopy). Screenees with colorectal cancer, polyps larger than 5 mm, three or more adenomas, adenomas 5 mm or smaller with a villous component of more than 20%, or severe dysplasia were referred for colonoscopy. Results: Of the 56 532 respondents (23.9% of those invited), 34 292 were enrolled and 17 148 were assigned to the screening group. Of those, 9999 attended and 9911 were actually examined by sigmoidoscopy. Distal adenomas were detected in 1070 subjects (10.8%). Proximal adenomas were detected in 116 of 747 (15.5%) subjects without cancer at sigmoidoscopy who then underwent colonoscopy. A total of 54 subjects was found to have colorectal cancer, a rate of 5.4 per 1000 (54% of which were Dukes' A). The procedures were relatively safe, with two perforations (one in 9911 sigmoidoscopy exams and one in 775 colonoscopies) and one hemorrhage requiring hospitalization after polypectomy during colonoscopy. The pain associated with sigmoidoscopy was described as mild or less than expected by 83.3% of the screenees. Conclusion: Sigmoidoscopy screening is generally acceptable to recipients and safe. The high yield of advanced adenomas is consistent with the projected impact of sigmoidoscopy screening on colorectal cancer incidence.
Taxane-Cisplatin-Fluorouracil As Induction Chemotherapy in Locally Advanced Head and Neck Cancers: An Individual Patient Data Meta-Analysis of the Meta-Analysis of Chemotherapy in Head and Neck Cancer Group
Authors: Pierre Blanchard, Jean Bourhis, Benjamin Lacas, Marshall R. Posner, Jan B. Vermorken, Juan J. Cruz Hernandez, Abderrahmane Bourredjem, Gilles Calais, Adriano Paccagnella, Ricardo Hitt, Jean-Pierre Pignon
Journal: Journal of Clinical Oncology (2013)

PURPOSE Cisplatin plus fluorouracil (PF) induction chemotherapy has been compared with taxane (docetaxel or paclitaxel), cisplatin, and fluorouracil (Tax-PF) in randomized trials in locoregionally advanced head and neck cancers (LAHNCs). The aim of this meta-analysis was to study the efficacy and toxicity of Tax-PF and PF and identify differences in outcomes in subsets of patients. METHODS Five randomized trials representing 1,772 patients were identified. Updated individual patient data (IPD) were retrieved for all trials. The log-rank test, stratified by trial, was used for comparison. Interaction or trend tests were used to study the interaction between covariates and treatment. Results Median follow-up was 4.9 years. The hazard ratio (HR) of death was 0.79 (95% CI, 0.70 to 0.89; P < .001; absolute benefit at 5 years: 7.4%) in favor of Tax-PF. Heterogeneity was significant (P = .08, I(2) = 51%) and related to one trial. There was no more heterogeneity after exclusion of this trial (P = .99, I(2) = 0%), and HR of death was 0.72 (95% CI, 0.63 to 0.83) in favor of Tax-PF. There was no interaction between treatment effect and the following patient covariates: age, sex, performance status, tumor stage, or site. Tax-PF was associated with significant reductions of progression, locoregional failure, and distant failure compared with PF, with HRs of 0.78 (95% CI, 0.69 to 0.87; P < .001), 0.79 (95% CI, 0.66 to 0.94; P = .007), and 0.63 (95% CI, 0.45 to 0.89; P = .009) respectively. CONCLUSION This IPD meta-analysis shows the superiority of Tax-PF over PF as induction chemotherapy. Its precise role in the management of LAHNC remains to be determined.
A piece of my mind. Frozen in time
Authors: R. Burns
Journal: JAMA (1994)

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