tbuckley/cabot-search huggingface dataset:
The atoll sign
Authors: S. L. F. Walsh, B. J. Roberton
Journal: Thorax (2010)

The atoll sign A man presented as an urgent referral to the interstitial lung disease outpatient clinic with a 5 week history of fever, night sweats, shortness of breath and malaise.His admission chest x-ray showed patchy consolidation within both lungs, and a subsequent CT demonstrated multiple parenchymal ring opacities (figure 1 and figure 2A).On the basis of the unusual CT appearances he subsequently proceeded to an open lung biopsy which demonstrated polypoid buds of intra-alveolar granulation tissue or Masson bodies, consistent with a histopathological diagnosis of organising pneumonia (figure 3).He was treated with intravenous methylprednisolone and hydroxychloroquine to which he initially responded.Over the next 5 years he had several relapses clinically and radiologically which required pulse doses of methylprednisolone.Once stable, his medication was tapered and eventually stopped.Repeat CT imaging at this time revealed no residual parenchymal abnormalities.No definite cause for his illness was found and, following a multidisciplinary evaluation of his case, a final diagnosis of cryptogenic organising pneumonia was made.Crescentic or ring-shaped opacities surrounding an area of ground-glass opacification occasionally seen in the setting of organising pneumonia were first described by Voloudaki 1 and later coined the 'Atoll sign' by Zompatori. 2Kim et al. documented it in 19% of cases of cryptogenic organising pneumonia. 3 The word Atoll is derived from the Maldivian word 'atholhu' meaning an island consisting of a circular coral reef surrounding a lagoon (figure 2B).Although originally thought to be specific for organising pneumonia, this CT appearance has been described in a variety of other diseases including sarcoidosis, 4 Wegener granulomatosis, 5 lymphomatoid granulomatosis, 6 pulmonary paracoccidiomycosis 7 and non-specific interstitial pneumonia, 8 and under different names including the 'reversedhalo' sign and the 'fairy-ring' sign.Histopathologically the ground-glass opacification centrally represents septal inflammation, and cellular debris within the airspaces and the peripheral crescentic or ring-shaped opacity represents organising pneumonia in the alveolar ducts. 1 From a learning perspective, although this striking CT appearance is well documented in organising pneumonia, it should alert the radiologist and physician to other possible diagnoses, of which Wegener granulomatosis is particularly important.
The effects of oxidized low density lipoproteins on inducible mouse macrophage gene expression are gene and stimulus dependent.
Authors: T A Hamilton, J A Major, G M Chisolm
Journal: Journal of Clinical Investigation (1995)

Oxidized LDL has been previously reported to suppress the expression of genes induced in mononuclear phagocytes by inflammatory stimuli. In this study we extend these findings to demonstrate that the suppressive effects of oxidized LDL vary depending upon the gene being monitored and the stimulus being used to induce or enhance its expression. The expression of a selection of LPS-inducible genes exhibited differential sensitivity to pretreatment with oxidized LDL. Furthermore, the ability of oxidized LDL to suppress gene expression varied markedly with the inducing stimulus used. TNF alpha and IP-10 mRNA expression induced by IFN gamma and IL-2 was markedly more sensitive to suppression by oxidized LDL than that induced by LPS. The cooperative effects of IFN gamma and LPS on the expression of the inducible nitric oxide synthase gene were suppressed by oxidized LDL while the antagonistic effect of IFN gamma on LPS-induced expression of the TNF receptor type II mRNA was not altered. The suppressive activity of LDL was acquired only after extensive oxidation and was localized in the extractable lipid component. These results suggest a potent and direct connection between the oxidative modification of LDL and the chronic inflammation seen in atherogenic lesions. Furthermore, the appreciable selectivity of oxidized LDL in mediating secondary control of cytokine gene expression demonstrates that the active material(s) is targeted to disrupt specific intracellular signaling pathways.
Effects of Hypertension and Its Reversal on the Thoracic Aorta of Male and Female Rats
Authors: HARVEY WOLINSKY
Journal: Circulation Research (1971)

Effects of hypertension and its reversal on the wall of the thoracic aorta of male and female rats were studied. Hypertension for 10 weeks caused increased diameter, wall thickness, tangential tension, wall stress, and medial area in both sexes. In addition, absolute amounts of elastin, collagen, and noncollagenous, alkali-soluble protein were significantly increased in the walls of all hypertensive vessels. Associated with the decrease of calculated tension and wall stress to normotensive levels after reversal of hypertension, wall thickness and medial area in males remained significantly greater than in controls and similar to the values found in hypertensive vessels, whereas in females these parameters returned fully to control levels. Absolute amounts of noncollagenous, alkali-soluble proteins did return to control levels after hypertension reversal, but elastin and collagen remained elevated in amounts similar to those in vessels with sustained hypertension; in females, this resulted in an above-normal concentration of these fibrous elements in the vessel wall. Compositional changes of the female vessel wall after reversal of hypertension were thus similar to but more clearcut and complete than those found in the male aorta. Recognition of irreversible changes in vessels subjected to hypertension may have implications for the benefits to be gained from blood pressure reduction on the progression of cardiovascular disease.
Ten years of evidence to guide physiotherapy interventions: Physiotherapy Evidence Database (PEDro)
Authors: Catherine Sherrington, Anne M Moseley, Robert D Herbert, Mark R Elkins, Christopher G Maher
Journal: British Journal of Sports Medicine (2009)

Clinicians are increasingly using evidence from high-quality clinical research to guide clinical decision making. Recent articles in this journal have examined research evidence to assist in clinical decisions as diverse as the prescription of running shoes,1 exercise therapy in the treatment of chronic disease2 and the use of protective equipment to prevent concussion.3

The most valid information about the effectiveness of healthcare interventions is provided by randomised controlled trials and systematic reviews of randomised controlled trials.4 The Physiotherapy Evidence Database (PEDro; http://www.pedro.org.au) provides easy access to randomised controlled trials and systematic reviews of physiotherapy interventions. PEDro also includes links to evidence-based clinical practice guidelines. October 2009 marked the 10th anniversary of the launch of PEDro.

PEDro is freely available on the internet. The database indexes citation details, author abstracts and, where available, links to full text for randomised controlled trials, systematic reviews and practice guidelines in physiotherapy. Although the PEDro database is designed primarily for health professionals, a subsite, called Physiotherapy Choices (http://www.physiotherapychoices.org.au), provides information in lay terms directly to consumers of physiotherapy services.

As of August 2009, more than 15 000 records (12 408 trials, 2060 reviews and 603 guidelines) have been indexed on PEDro. Each record is coded according to the subdiscipline(s) of physiotherapy it addresses. PEDro now includes 615 randomised controlled trials and 102 …
Effect of CO <sub>2</sub> Insufflation on the Number and Behavior of Air Microemboli in Open-Heart Surgery
Authors: P. Svenarud, M. Persson, J. van der Linden
Journal: Circulation (2004)

The risks that the presence of air microemboli implies in open-heart surgery have recently been emphasized by reports that their number is correlated with the degree of postoperative neuropsychological disorder. Therefore, we studied the effect of CO2 insufflation into the cardiothoracic wound on the incidence and behavior of microemboli in the heart and ascending aorta.Twenty patients undergoing single-valve surgery were randomly divided into 2 groups. Ten patients were insufflated with CO2 via a gas diffuser, and 10 were not. Microemboli were ascertained by intraoperative transesophageal echocardiography (TEE) and recorded on videotape from the moment that the aortic cross-clamp was released until 20 minutes after end of cardiopulmonary bypass (CPB). The surgeon performed standard de-airing maneuvers without being aware of TEE findings. Postoperatively, a blinded assessor determined the maximal number of gas emboli during each consecutive minute in the left atrium, left ventricle, and ascending aorta. The 2 groups did not differ in the usual clinical parameters. The median number of microemboli registered during the whole study period was 161 in the CO2 group versus 723 in the control group (P<0.001). Corresponding numbers for the left atrium were 69 versus 340 (P<0.001), left ventricle 68 versus 254 (P<0.001), and ascending aorta 56 versus 185 (P<0.001). In the CO2 group, the median number of detectable microemboli after CPB fell to zero 7 minutes after CPB versus 19 minutes in the control group (P<0.001).Insufflation of CO2 into the thoracic wound markedly decreases the incidence of microemboli.
Vessel-building mast cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Irradiation instructs mast cells to rebuild blood vessels in oxygen-deprived tissues, according to Heissig and colleagues on page 739. Low-dose irradiation mobilized adult and precursor mast cells, which traveled to the ischemic tissue and produced the vessel-building growth factor VEGF (vascular endothelial growth factor).






Figure 

Low-dose irradiation enhances limb regeneration (bottom) unless mast cells are absent (top).




Ionizing irradiation has been shown to promote the growth of new blood vessels through the induction of VEGF and inhibition of endothelial cell death. However, the primary source of irradiation-induced VEGF and the precise mechanism that triggers its production were not clear. Mast cells—well-known for their production of histamine in allergic responses—had been found in tissues undergoing angiogenesis. Mast cells are also capable of producing VEGF, but whether these cells play a leading or supporting role in angiogenesis had not been explored.Heissig et al. now show that mast cells are essential for irradiation-induced vessel growth in a mouse model of ischemic limb injury. Irradiation-induced cellular damage triggers the production of the degradative enzyme matrix metalloprotease-9 (MMP-9) by largely unknown mechanisms. In this model, local irradiation of the damaged limb increased MMP-9 production in the ischemic tissue, which liberated the cytokine Kit ligand (KitL), likely from stromal cells. KitL then attracted VEGF-producing mast cells into the injured tissue.

At the same time, irradiation mobilized mast cell precursors and endothelial cell progenitors from the bone marrow, and some of these cells became incorporated into the growing vessels. Without mast cells, the vessel-building benefits of irradiation were lost. The authors thus speculate that localized irradiation might improve upon current therapies for organ regeneration, which rely on the injection of large numbers of bone marrow–derived stem cells directly into damaged organs.
Osteogenesis by human mesenchymal stem cells cultured on silk biomaterials: Comparison of adenovirus mediated gene transfer and protein delivery of BMP-2
Authors: Lorenz Meinel, Sandra Hofmann, Oliver Betz, Robert Fajardo, Hans P. Merkle, Robert Langer, Christopher H. Evans, Gordana Vunjak-Novakovic, David L. Kaplan
Journal: Biomaterials (2006)
Proliferation cell nuclear antigen (clone 19A2) correlates with 5-bromo-2-deoxyuridine labelling in human colonic epithelium.
Authors: U M Weisgerber, H Boeing, R Nemitz, R Raedsch, R Waldherr
Journal: Gut (1993)

Measurements of cell proliferation can be used as biomarkers of preneoplastic change. In this study, two immunocytochemical methods that measure different components of the cell cycle were compared to assess cell proliferation on biopsy samples from human colonic mucosa. These methods are based on a monoclonal antibody against 5-bromo-2-deoxyuridine (BrdU), which is confined to S phase cells, and a more broad assessment of proliferation based on an antibody against proliferating cell nuclear antigen (PCNA, clone 19A2). In the PCNA assay, only strongly immunostained nuclei were included. The proliferation index was assessed in colonic mucosa from patients with no colonic disorders. Correlation between individual total proliferation indices determined by either method was significant with rs = 0.6 (p < 0.05). The mean proliferation index in the study group was 7.79% using BrdU and 7.64% using PCNA immunocytochemistry. Distribution of labelled cells within crypts was similar with respect to the two methods with a peak at the 18th and the 24th percentile in the case of BrdU and at the 23rd percentile for PCNA. Variance component analysis showed that at least two biopsy specimens should be evaluated per subject to allow a precise individual characterisation. It is concluded that PCNA (19A2) immunocytochemistry may be used as an operational marker of cell proliferation in normal colonic mucosa. A significant correlation and an agreement in the mean proliferation index between PCNA (19A2) and BrdU can only be achieved by a strictly standardised enumeration of labelled cells limited to strongly stained nuclei in the PCNA evaluation.
Paracrine signals from liver sinusoidal endothelium regulate hepatitis C virus replication
Authors: Ian A. Rowe, Sukhdeep K. Galsinh, Garrick K. Wilson, Richard Parker, Sarah Durant, Catalin Lazar, Norica Branza-Nichita, Roy Bicknell, David H. Adams, Peter Balfe, Jane A. McKeating
Journal: Hepatology (2013)

Hepatitis C virus (HCV) is a major cause of global morbidity, causing chronic liver injury that can progress to cirrhosis and hepatocellular carcinoma. The liver is a large and complex organ containing multiple cell types, including hepatocytes, sinusoidal endothelial cells (LSEC), Kupffer cells, and biliary epithelial cells. Hepatocytes are the major reservoir supporting HCV replication; however, the role of nonparenchymal cells in the viral lifecycle remains largely unexplored. LSEC secrete factors that promote HCV infection and transcript analysis identified bone morphogenetic protein 4 (BMP4) as a candidate endothelial-expressed proviral molecule. Recombinant BMP4 increased HCV replication and neutralization of BMP4 abrogated the proviral activity of LSEC-conditioned media. Importantly, BMP4 expression was negatively regulated by vascular endothelial growth factor A (VEGF-A) by way of a VEGF receptor-2 (VEGFR-2) primed activation of p38 MAPK. Consistent with our in vitro observations, we demonstrate that in normal liver VEGFR-2 is activated and BMP4 expression is suppressed. In contrast, in chronic liver disease including HCV infection where there is marked endothelial cell proliferation, we observed reduced endothelial cell VEGFR-2 activation and a concomitant increase in BMP4 expression. Conclusion : These studies identify a role for LSEC and BMP4 in HCV infection and highlight BMP4 as a new therapeutic target for treating individuals with liver disease. (Hepatology 2014;59:375–384)
Intravenous immunoglobulin treatment of experimental T cell-mediated autoimmune disease. Upregulation of T cell proliferation and downregulation of tumor necrosis factor alpha secretion.
Authors: A Achiron, R Margalit, R Hershkoviz, D Markovits, T Reshef, E Melamed, I R Cohen, O Lider
Journal: Journal of Clinical Investigation (1994)

It has been reported previously that intravenous administration of normal human immunoglobulins (IVIg) to human patients can suppress the clinical signs of certain autoimmune diseases. However, the mechanism(s) by which normal Ig interferes with the various disorders and the scheduling of treatment have been poorly delineated. To study these questions, we examined IVIg treatment of two experimentally induced T cell autoimmune diseases in rats: experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA). We now report that IVIg treatment (0.4 g/kg) inhibited the active induction of both EAE and AA, and that this treatment did not affect the acquisition of resistance to reinduction of EAE. The importance of the site of administration and schedule of treatment were studied in the AA model. Ig was effective when given intravenously, but not when administrated subcutaneously or intraperitoneally. IVIg treatment was effective when given daily from immunization to outbreak of disease; but it was also effective when given once at the time of immunization or once 2 wk after induction of AA, just at the clinical outbreak of disease. Administration of IVIg between immunization and outbreak of AA was less effective. Prevention of disease by IVIg occurred despite the presence of T cell reactivity to the specific antigens in the disease. In fact, IVIg administrated to naive rats activated T cell reactivity to some self-antigens. Nevertheless, IVIg treatment led to decreased production of the inflammatory cytokine TNF alpha. Thus, IVIg treatment may exert its therapeutic power not by inhibiting T cell recognition of self-antigens, but by inhibiting the biological consequences of T cell recognition.
Can Erlotinib Ameliorate Cisplatin-Induced Toxicities?
Authors: Jason A. Sprowl, Ron H. Mathijssen, Alex Sparreboom
Journal: Journal of Clinical Oncology (2013)

izedphaseIIclinicaltrialthatdemonstratedaddingerlotinibtocisplatin and radiotherapy failed to significantly increase response rates or progression-free survival in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). The incentive for the study was based on the notion that the target of erlotinib, the epidermal growth factor receptor (EGFR), is overexpressed in more than 90% of SCCHN, and the previous observation that patients with this disease seem to benefit from cetuximab, a chimeric antibody against EGFR. 2,3 As mentioned by Hansen and Siu in the accompanying editorial, 4 the study by Martins et al is one of several trials suggesting that there is no therapeutic benefit of small molecule tyrosine kinase inhibitors that target EGFR in the treatment of SCCHN. One particularly interesting observation reported by Martins
Meta-Analysis: Exercise Therapy for Nonspecific Low Back Pain
Authors: Jill A. Hayden, Maurits W. van Tulder, Antti V. Malmivaara, Bart W. Koes
Journal: Annals of Internal Medicine (2005)

Background: Exercise therapy is widely used as an intervention in low back pain. Objective: To evaluate the effectiveness of exercise therapy in adult nonspecific acute, subacute, and chronic low back pain versus no treatment and other conservative treatments. Data Sources: MEDLINE, EMBASE, PsychInfo, CINAHL, and Cochrane Library databases to October 2004; citation searches and bibliographic reviews of previous systematic reviews. Study Selection: Randomized, controlled trials evaluating exercise therapy for adult nonspecific low back pain and measuring pain, function, return to work or absenteeism, and global improvement outcomes. Data Extraction: Two reviewers independently selected studies and extracted data on study characteristics, quality, and outcomes at short-, intermediate-, and long-term follow-up. Data Synthesis: 61 randomized, controlled trials (6390 participants) met inclusion criteria: acute (11 trials), subacute (6 trials), and chronic (43 trials) low back pain (1 trial was unclear). Evidence suggests that exercise therapy is effective in chronic back pain relative to comparisons at all follow-up periods. Pooled mean improvement (of 100 points) was 7.3 points (95% CI, 3.7 to 10.9 points) for pain and 2.5 points (CI, 1.0 to 3.9 points) for function at earliest follow-up. In studies investigating patients (people seeking care for back pain), mean improvement was 13.3 points (CI, 5.5 to 21.1 points) for pain and 6.9 points (CI, 2.2 to 11.7 points) for function, compared with studies where some participants had been recruited from a general population (for example, with advertisements). Some evidence suggests effectiveness of a graded-activity exercise program in subacute low back pain in occupational settings, although the evidence for other types of exercise therapy in other populations is inconsistent. In acute low back pain, exercise therapy and other programs were equally effective (pain, 0.03 point [CI, −1.3 to 1.4 points]). Limitations: Limitations of the literature, including low-quality studies with heterogeneous outcome measures inconsistent and poor reporting, and possibility of publication bias. Conclusions: Exercise therapy seems to be slightly effective at decreasing pain and improving function in adults with chronic low back pain, particularly in health care populations. In subacute low back pain populations, some evidence suggests that a graded-activity program improves absenteeism outcomes, although evidence for other types of exercise is unclear. In acute low back pain populations, exercise therapy is as effective as either no treatment or other conservative treatments.
A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer
Authors: G. Deplanque, M. Demarchi, M. Hebbar, P. Flynn, B. Melichar, J. Atkins, E. Nowara, L. Moyé, D. Piquemal, D. Ritter, P. Dubreuil, C.D. Mansfield, Y. Acin, A. Moussy, O. Hermine, P. Hammel
Journal: Annals of Oncology (2015)

BackgroundMasitinib is a selective oral tyrosine–kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC).Patients and methodsPatients with inoperable, chemotherapy-naïve, PDAC were randomized (1: 1) to receive gemcitabine (1000 mg/m2) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic.ResultsThree hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl–CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable.ConclusionsThe present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation.Trial RegistrationClinicalTrials.gov:NCT00789633.