tbuckley/cabot-search huggingface dataset:
Management of incidental lung parenchymal lesions found on CT pulmonary angiograms
Authors: Sharlina Sallehuddin, Said Isse, Peter Russell, Supriya Sundaram
Journal: European Respiratory Journal (2011)

Introduction: Incidental findings of lung parenchymal lesions are common. Many studies have described what these alternative diagnoses are, but few have looked at their management. We aim to investigate how these are managed in a UK district general hospital.

Methods: We retrospectively analysed all CTPAs undertaken in 2008. We used Picture Archiving and Communication System (PACS) for CTPA reports, Pathweb for biopsy results and multidisciplinary team (MDT) database and patient case notes for the final clinical outcome.

Results: 

![Figure][1] 



As a result 15 had a PET scan of which 9 were FDG-avid and 7 proceeded to a tissue biopsy. Ten patients (11.6%) had positive histology. 5 had locally advanced or metastatic non-small cell lung cancer, 3 had squamous cell carcinoma, two had other metastatic carcinomas. Time from CTPA to histological diagnosis was more than 21 days for 7 patients. Three patients were referred for curative surgery (lobectomy/VATS), four patients to oncology (palliative radiotherapy/chemotherapy), three patients referred for palliative care.

Conclusion: Incidental findings on CTPAs have generated additional work for the respiratory department and lung multidisciplinary team. Patients with positive histology had advanced carcinoma and the incidental finding of lung cancer was associated with a poor prognosis. Incidental findings of these lesions require standardised follow-up and management plans in order to avoid delays.

 [1]: pending:yes
Expression, regulation, and function of αV integrins in hepatocellular carcinoma: An<i>in vivo</i>and<i>in vitro</i>study
Authors: Mimoun Nejjari, Zakia Hafdi, Géraldine Gouysse, Michelangelo Fiorentino, Olivier Béatrix, Jérôme Dumortier, Céline Pourreyron, Chiara Barozzi, Antonia D’Errico, Walter F. Grigioni, Jean-Yves Scoazec
Journal: Hepatology (2002)

The expression of αV integrins by neoplastic cells contributes to the promotion of local invasion and metastasis. The most characteristic extracellular ligands of αV integrins are vitronectin and fibronectin. Hepatocytes are the main source of vitronectin, and the capacity to synthesize and secrete vitronectin is usually retained in hepatocellular carcinoma. The aim of this study was to explore the expression, regulation, and functional role of αV integrins in hepatocellular carcinoma. We first analyzed the expression of αV integrins and their ligands fibronectin and vitronectin in 80 cases of hepatocellular carcinoma. αV integrin chain was detected in 44 cases and vitronectin in 50. Twenty-four of the 44 αV-positive tumors contained large amounts of vitronectin. These cases presented more frequently with adverse histoprognostic factors, including infiltrative growth pattern (62.5%), lack of capsule (71%), presence of capsular invasion (57%), and satellite nodules (50%). We then used HepG2 and Hep3B cell lines as in vitro models to study αV integrin regulation and function. HepG2 and Hep3B cells expressed αV integrin chain and used αVβ1 and αVβ5 for adhesion and migration on vitronectin. Tumor necrosis factor (TNF) α and transforming growth factor (TGF) β significantly increased the expression levels of αV integrins and stimulated the adhesion and migration of both HepG2 and Hep3B cell lines on vitronectin. The effects of growth factors on cell adhesion and migration were reproduced by incubation with conditioned medium from rat liver myofibroblasts. In conclusion, our results support the existence of an αV integrin/vitronectin connection in hepatocellular carcinoma and suggest that this connection may be an adverse prognostic factor.
Cost of Anaesthetic Agents
Authors: C. L. Hewer
Journal: BMJ (1969)

<h3>Background</h3> Natural killer (NK) cells provide important immune protection from cancer and are a key requirement for particular immunotherapies. There is accumulating evidence that NK cells become dysfunctional during cancer. Overcoming NK cell exhaustion would be an important step to allow them to function optimally in a range of NK cell therapies, including those that depend on autologos circulating NK cells. We have previously demonstrated that NK cells undergo a normal metabolic reprogramming in response to cytokine activation and that this is required for optimal function. The objective of this work was to investigate if cellular metabolism of circulating NK cells is dysregulated in patients with metastatic breast cancer and if so, to gain insights into potential mechanisms underpinning this. Such discoveries would provide important insights into how to unleash the full activity of NK cells for maximum immunotherapy output. <h3>Methods</h3> Single-cell analysis, metabolic flux and confocal analysis of NK cells from patients with metastatic breast cancer and healthy controls <h3>Results</h3> In addition to reduced interferon-γ production and cytotoxicity, peripheral blood NK cells from patients had clear metabolic deficits including reduced glycolysis and oxidative phosphorylation. There were also distinct morphologically alterations in the mitochondria with increased mitochondrial fragmentation observed. Transforminggrowth factor-β (TGFβ) was identified as a key driver of this phenotype as blocking its activity reversed many metabolic and functional readouts. Expression of glycoprotein-A repetitions predominant (GARP) and latency associated peptide (LAP), which are involved with a novel TGFβ processing pathway, was increased on NK cells from some patients. Blocking the GARP–TGFβ axis recapitulated the effects of TGFβ neutralization, highlighting GARP as a novel NK cell immunotherapy target for the first time. <h3>Conclusions</h3> TGFβ contributes to metabolic dysfunction of circulating NK cells in patients with metastatic breast cancer. Blocking TGFβ and/or GARP can restore NK cell metabolism and function and is an important target for improving NK cell-based immunotherapies.
Adverse Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption
Authors: Orfeu M. Buxton, Sean W. Cain, Shawn P. O’Connor, James H. Porter, Jeanne F. Duffy, Wei Wang, Charles A. Czeisler, Steven A. Shea
Journal: Science Translational Medicine (2012)

Epidemiological studies link short sleep duration and circadian disruption with higher risk of metabolic syndrome and diabetes. We tested the hypotheses that prolonged sleep restriction with concurrent circadian disruption, as can occur in people performing shift work, impairs glucose regulation and metabolism. Healthy adults spent >5 weeks under controlled laboratory conditions in which they experienced an initial baseline segment of optimal sleep, 3 weeks of sleep restriction (5.6 hours of sleep per 24 hours) combined with circadian disruption (recurring 28-hour "days"), followed by 9 days of recovery sleep with circadian re-entrainment. Exposure to prolonged sleep restriction with concurrent circadian disruption, with measurements taken at the same circadian phase, decreased the participants' resting metabolic rate and increased plasma glucose concentrations after a meal, an effect resulting from inadequate pancreatic insulin secretion. These parameters normalized during the 9 days of recovery sleep and stable circadian re-entrainment. Thus, in humans, prolonged sleep restriction with concurrent circadian disruption alters metabolism and could increase the risk of obesity and diabetes.
Resident alveolar macrophages mediate early alveolar epithelial death signaling and dysfunction
Authors: Brijesh Patel, Michael Wilson, Masao Takata
Journal: European Respiratory Journal (2012)

Acute lung injury (ALI) is characterized by alveolar epithelial dysfunction. We previously showed that early epithelial dysfunction was specifically mediated through tumor necrosis factor (TNF) p55 receptor signaling [1]. This study examined the contribution of resident alveolar macrophages (AM) to this phenomenon following acid aspiration.

C57Bl6 mice were treated intratracheally with liposomes containing either clodronate or PBS. After 48 hours, they underwent intratracheal instillation of hydrochloric acid followed by mechanical ventilation to assess respiratory parameters. Oxygenation, respiratory elastance, alveolar TNF concentration, lung caspase-8 activity and alveolar fluid clearance (AFC) were measured at 90 minutes after acid instillation.

Clodronate liposomes produced an 80% depletion of AMs. AM depletion significantly improved the deterioration in respiratory elastance (cmH2O/µl: PBS=0.06±0.008; CLOD=0.05±0.004; p<0.05) and PaO2:FiO2 (PBS=304±113; CLOD=426±41; P<0.05) induced by acid instillation. Additionally, alveolar TNF was significantly reduced (pg/ml: PBS=46.5±25.8; CLOD=15.5±2.7; P<0.05), along with attenuated lung caspase-8 activity (arbitrary units: PBS=14763±5466; CLOD=7135±372; P<0.01), and improved AFC (%/30min: PBS=3.8±2.6; CLOD=7.1±2.4; P<0.05). Caspase-8 activity showed an inverse correlation to AFC (Pearson r=-0.766; P<0.0001) implying epithelial death receptor activation.

These data suggests that during ALI induced by acid aspiration, epithelial dysfunction and hypoxemia are a result of epithelial cell death receptor activation by alveolar macrophage-derived TNF.

[1] Patel et al . Intensive Care Med. 2011;37(Supplement):S205

Supported by Wellcome Trust, UK.
Mycophenolic acid
Authors: R Ziswiler, K Steinmann-Niggli, A Kappeler, C Daniel, H P Marti
Journal: Journal of the American Society of Nephrology (1998)

Mycophenolate mofetil (MMF) represents a powerful immunosuppressant in organ transplantation. The aim of this study was to determine the anti-inflammatory effects of MMF on mesangial cells. Cultured rat mesangial cells were exposed to mycophenolic acid (MPA) in concentrations of 0.1 to 10 microM. MPA inhibited the proliferation of these cells in a dose-dependent manner. A maximum of 98% inhibition was obtained by a 2-d exposure of mesangial cells to > or =5 microM MPA. As expected, the addition of > or =75 microM guanosine prevented the antiproliferative effect of MPA completely. Subsequently, in vivo studies were performed in the anti-Thy1.1 nephritis model. Sixty-six male Wistar rats were investigated: healthy rats (n = 15), treated healthy rats (n = 6), nephritic rats (n = 15), and treated nephritic rats (n = 30). MMF therapy (40 mg/kg body wt per d) of nephritic animals was initiated 2 d before (n = 3) and 6 h (n = 15) or 2 d (n = 12) after induction of nephritis. Renal histology was analyzed at days +6 and +9 after initiation of disease. Therapy of nephritic rats by MMF resulted in a significant amelioration of glomerular histology, assessed by glomerular cellularity, synthesis of alpha-smooth muscle actin, extracellular matrix deposition, and glomerular hypertrophy. Proteinuria, expressed as areas under the curve of protein/creatinine ratios versus time, showed a clear tendency toward a reduction by MMF therapy. Healthy control rats were not negatively affected by exposure to MMF. In summary, this study shows that mesangial cell proliferation can be significantly inhibited by MPA in vitro and in vivo. MMF represents a new approach to the therapy of experimental mesangial cell-mediated forms of glomerulonephritis.
Protective effect of hyperbaric oxygen for the temporary ischaemic myocardium. Macroscopic and histological data
Authors: M. KAWAMURA, K. SAKAKIBARA, B. SAKAKIBARA, H. KIDOKORO, H. TAKAHASHI, S. KOBAYASHI, S. KONISHI, Y. UNO
Journal: Cardiovascular Research (1976)

A protective effect of hyperbaric oxygen immediately after reopening of occluded coronary blood flow for the temporary ischaemic myocardial muscle was studied. Thirty dogs were used in this study, and 20 dogs were sacrificed after 4 h and 10 dogs were sacrificed after 5 d. Temporary occlusion of coronary artery (from 30 min to 2 h) was produced by ligation. One group were controls and the other group were a hyperbaric group in which dogs breathed 100% oxygen at an absolute pressure of 2 atmospheres before and after release of coronary ligation. The macroscopic extent of ischaemic area was studied by using nitroblue tetrazolium and microscopic and ECG findings were examined. By breathing oxygen at high pressure immediately after reopening of occluded coronary blood flow, the ischaemic area was markedly reduced. In such cases, some myocardial muscles around the arterioles and sinusoids, even when these vessels existed in the ischaemic area, were kept in a viable state. The repair of necrotic myocardial muscles was promoted histologically. Serious arrhythmia, especially ventricular fibrillation, was also well suppressed, and the stable haemodynamic conditions were obtained during operative procedures. No harmful side effects of hyperbaric oxygen were observed. One of the most effective treatments of acute myocardial infarction involves reconstruction of the occluded coronary artery as soon as possible after the onset of myocardial infarction by using these advantages of hyperbaric oxygen.
Beneficial effects of dopamine combined with intravenous nitroglycerin on hemodynamics in patients with severe left ventricular failure.
Authors: H S Loeb, J P Ostrenga, W Gaul, J Witt, G Freeman, P Scanlon, R M Gunnar
Journal: Circulation (1983)

Hemodynamic effects of dopamine and intravenous nitroglycerin alone, and in combination, were studied in 27 patients with severe left ventricular failure. Dopamine alone increased cardiac index from 1.8 to 2.5 l/min/m2 but also increased wedge pressure from 24 to 30 mm Hg and heart rate from 88 to 101 beats/min. Arterial oxygen saturation fell from 92% to 87% (p less than .001). Nitroglycerin alone had a lesser effect on cardiac index (1.8 to 2.2 l/min/m2) but decreased wedge pressure from 26 to 16 mm Hg and heart rate from 91 to 86 beats/min. Arterial oxygen saturation fell from 91% to 90% (NS). Combined dopamine and nitroglycerin administration resulted in optimal hemodynamics, with cardiac index of 2.9 l/min/m2, wedge pressure of 17 mm Hg, and heart rate of 96 beats/min. Arterial oxygen saturation remained low at 88% in spite of the reduction in left ventricular filling pressure, which probably reflects increased intrapulmonary right-to-left shunting coupled with increased pulmonary blood flow. These results suggest that the combination of dopamine with intravenous nitroglycerin should be considered for patients with severe left ventricular dysfunction who require temporary pharmacologic support.
MEDICAL, PSYCHIATRIC, AND LEGAL ASPECTS OF PREMENSTRUAL TENSION
Authors: IRWIN N. PERR
Journal: American Journal of Psychiatry (1958)

Various aspects of the problem of the premenstrual tension syndrome have been discussed–from medical, psychiatric, and legal viewpoints. The syndrome has been defined with comments on frequency and symptoms with some elaboration on physiological changes and theories of etiology. This in turn has been correlated as much as possible with psychiatric findings, and lastly the relationship of the syndrome to legal considerations has been briefly discussed.
Aspirin Use, Tumor<i>PIK3CA</i>Mutation, and Colorectal-Cancer Survival
Authors: Xiaoyun Liao, Paul Lochhead, Reiko Nishihara, Teppei Morikawa, Aya Kuchiba, Mai Yamauchi, Yu Imamura, Zhi Rong Qian, Yoshifumi Baba, Kaori Shima, Ruifang Sun, Katsuhiko Nosho, Jeffrey A. Meyerhardt, Edward Giovannucci, Charles S. Fuchs, Andrew T. Chan, Shuji Ogino
Journal: New England Journal of Medicine (2012)

Regular use of aspirin after a diagnosis of colon cancer has been associated with a superior clinical outcome. Experimental evidence suggests that inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2) (also known as cyclooxygenase-2) by aspirin down-regulates phosphatidylinositol 3-kinase (PI3K) signaling activity. We hypothesized that the effect of aspirin on survival and prognosis in patients with cancers characterized by mutated PIK3CA (the phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit alpha polypeptide gene) might differ from the effect among those with wild-type PIK3CA cancers.We obtained data on 964 patients with rectal or colon cancer from the Nurses' Health Study and the Health Professionals Follow-up Study, including data on aspirin use after diagnosis and the presence or absence of PIK3CA mutation. We used a Cox proportional-hazards model to compute the multivariate hazard ratio for death. We examined tumor markers, including PTGS2, phosphorylated AKT, KRAS, BRAF, microsatellite instability, CpG island methylator phenotype, and methylation of long interspersed nucleotide element 1.Among patients with mutated-PIK3CA colorectal cancers, regular use of aspirin after diagnosis was associated with superior colorectal cancer-specific survival (multivariate hazard ratio for cancer-related death, 0.18; 95% confidence interval [CI], 0.06 to 0.61; P<0.001 by the log-rank test) and overall survival (multivariate hazard ratio for death from any cause, 0.54; 95% CI, 0.31 to 0.94; P=0.01 by the log-rank test). In contrast, among patients with wild-type PIK3CA, regular use of aspirin after diagnosis was not associated with colorectal cancer-specific survival (multivariate hazard ratio, 0.96; 95% CI, 0.69 to 1.32; P=0.76 by the log-rank test; P=0.009 for interaction between aspirin and PIK3CA variables) or overall survival (multivariate hazard ratio, 0.94; 95% CI, 0.75 to 1.17; P=0.96 by the log-rank test; P=0.07 for interaction).Regular use of aspirin after diagnosis was associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. The findings from this molecular pathological epidemiology study suggest that the PIK3CA mutation in colorectal cancer may serve as a predictive molecular biomarker for adjuvant aspirin therapy. (Funded by The National Institutes of Health and others.).
Prospective Evaluation of Risk Factors for Male Breast Cancer
Authors: L. A. Brinton, D. A. Richesson, G. L. Gierach, J. V. Lacey, Y. Park, A. R. Hollenbeck, A. Schatzkin
Journal: JNCI Journal of the National Cancer Institute (2008)

Most risk factors for male breast cancer have been derived from retrospective studies that may reflect selective recall. In the prospective National Institutes of Health–AARP Diet and Health Study, we studied 324 920 men, among whom 121 developed breast cancer. Men who reported a first-degree relative with breast cancer had an increased risk of breast cancer (relative risk [RR] = 1.92, 95% confidence interval [CI] = 1.19 to 3.09). Among the medical conditions examined, a new finding emerged regarding increased male breast cancer risk associated with a history of a bone fracture (RR = 2.20, 95% CI = 1.24 to 3.91). Obesity was positively related to risk (RR = 1.79, 95% CI = 1.10 to 2.91, for body mass indices of ≥30 vs <25 kg/m 2 ) and physical activity inversely related, even after adjustment for body mass index. Smokers were at somewhat elevated risk, although trends with smoking characteristics were inconsistent. Alcohol consumption was not related to risk. The identified risk factors show some commonalities with female breast cancer and indicate the importance of hormonal mechanisms. Differences in risk factors may reflect unique mechanisms associated with androgens and their ratio to bioavailable estrogens.
ERK signaling is a central regulator for BMP-4 dependent capillary sprouting
Authors: Q ZHOU, J HEINKE, A VARGAS, S WINNIK, T KRAUSS, C BODE, C PATTERSON, M MOSER
Journal: Cardiovascular Research (2007)

Objective Bone Morphogenetic Protein-4 (BMP-4) and Extracellular-Signal Regulated Kinases (ERK) play crucial roles in vascular diseases. Here, we demonstrate that BMP-4 not only signals through the classical Smad cascade but also activates ERK phosphorylation as an alternative pathway in human umbilical vein endothelial cells (HUVEC) and that Smad and ERK pathways communicate through signal crosstalk.
An Arctic Moon
Authors: James L. Glazer
Journal: Annals of Internal Medicine (2005)

On Being a Doctor6 December 2005An Arctic MoonJames L. Glazer, MDJames L. Glazer, MDFrom Maine Medical Center, Portland, ME 04101.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-11-200512060-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail "You don't need to worry about my eye," Doc said as he squinted up at me through the bright lights of the trauma bay. "The left one is glass anyway!" A conspiratorial smile spread across his face, compressed and molded by the ill-fitting cervical collar.Moments earlier, Doc had been brought into the emergency room. Elderly, hard of hearing, and sporting a chart full of comorbidities, he had driven his ATV into the back of a road grader. The piece of heavy machinery rolled backwards, crushing him beneath its wheels. Here in northwestern Alaska there is no pavement, and ATVs ... Author, Article, and Disclosure InformationAffiliations: From Maine Medical Center, Portland, ME 04101.Corresponding Author: James L. Glazer, MD, Maine Medical Center, 272 Congress Street, Portland, ME 04101; e-mail, [email protected]org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 December 2005Volume 143, Issue 11Page: 842-843KeywordsBloodChartsElderlyHearingShouldersSurgeonsVision ePublished: 6 December 2005 Issue Published: 6 December 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Controlled Trial of Naturalistic Dawn Simulation and Negative Air Ionization for Seasonal Affective Disorder
Authors: Michael Terman, Jiuan Su Terman
Journal: American Journal of Psychiatry (2006)

This trial assessed two novel nonpharmaceutical treatments for winter depression-naturalistic dawn simulation and high-density negative air ionization-delivered during the final hours of sleep.The patients were 99 adults (77 women and 22 men) with the winter seasonal pattern of major depressive disorder (94 cases) and bipolar II disorder (five cases). Five parallel groups received 1) dawn simulation (0.0003-250 lux in the pattern of May 5 at 45 degrees north latitude); 2) a dawn light pulse (13 minutes, 250 lux, with an illuminant dose of 3.25x10(3) lux-minutes matched to the simulated dawn); 3) postawakening bright light (30 minutes, 10,000 lux); 4) negative air ionization at high flow rate (93 minutes, 4.5x10(14 )ions/second); or 5) ionization at low flow rate (93 minutes, 1.7x10(11) ions/second). The symptoms were assessed over 3 weeks with the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version.Posttreatment improvement results were bright light, 57.1%; dawn simulation, 49.5%; dawn pulse, 42.7%; high-density ions, 47.9%; and low-density ions, 22.7% (significantly lower than the others). Contrary to the authors' hypothesis, analysis of variance failed to find superiority of dawn simulation to the dawn pulse or bright light. However, the dawn pulse led to a pattern of residual or exacerbated depressive symptoms similar to those seen in low-density ion nonresponders.Naturalistic dawn simulation and high-density ionization are active antidepressants that do not require the effort of postawakening bright light therapy. They can be considered candidate alternatives to bright light or medication.
How to Train Your Biomarker: Fig. 1.
Authors: Douglas Yee
Journal: Clinical Cancer Research (2010)

Type I insulin-like growth factor (IGF) receptor (IGF1R) inhibitors are new cancer therapies. Pitts and colleagues used in vitro data to "train" a predictive biomarker for an IGF1R tyrosine kinase inhibitor. Given the complexity of IGF signaling, additional layers of biomarker analysis will likely be needed to develop predictive factors.