tbuckley/cabot-search huggingface dataset:
Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study
Authors: Stephen M Ansell, Hui Tang, Paul J Kurtin, Patricia A Koenig, David J Inwards, Keith Shah, Steven C Ziesmer, Andrew L Feldman, Radha Rao, Mamta Gupta, Charles Erlichman, Thomas E Witzig
Journal: The Lancet Oncology (2011)
Frequency and route of administration in the treatment of experimental arthritis by phosphorus-based dendrimer
Authors: Myriam Hayder, Mary Poupot, Michel Baron, Cédric-Olivier Turrin, Anne-Marie Caminade, Jean-Pierre Majoral, Robert A Eisenberg, Jean-Jacques Fournié, Alain Cantagrel, Rémy Poupot, Jean-Luc Davignon
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> The authors have previously shown that phosphorus-based dendrimer ABP targets monocytes to inhibit inflammation and osteoclastogenesis in two models of experimental arthritis. The authors have now further explored this model and tested the frequency and route of administration of dendrimer ABP. <h3>Materials and methods</h3> The authors used two models of mouse arthritis: IL-1 ra-/- which develops a spontaneous arthritis at the age of 6 weeks. The KxB/N serum transfer arthritis, which is more severe, and develops upon the injection of auto-antibodies from KxB/N mice. Inflammation and paw-swelling were scored, cytokines were measured by Elisa, and histology was performed. <h3>Results</h3> In the IL-1 ra-/- model of spontaneous arthritis, the i.v. injection of dendrimer was found to be optimal when administered every 3 weeks. To test for other route of administration, gavage was also performed once a week after solubilisation of dendrimer in an aqueous buffer. This suggests that dendrimer ABP is not degraded in the gastrointestinal tract and is absorbed efficiently using this route of administration. In the KxB/N serum transfer model, which is more severe, several i.p. injections of serum interspaced with dendrimer ABP (every 3 days over the course of the experiment) were performed. The authors showed that injections of KxB/N serum (days 0 and 2) induced arthritis which was well controlled by dendrimer. Subsequent injection of serum (day 11) reactivated arthritis, thus mimicking flares of arthritis that are observed in RA. Again, arthritis was controlled by dendrimer. On day 20, 3 days after the last injection of serum performed on day 17, mice were euthanised and blood drawn for analysis. Quantification of serum pro-inflammatory cytokines (IL-1β, TNFα, IL-6, IL-17) showed that i.v. dendrimer completely abrogated the inflammation seen in untreated arthritic mice. Bone destruction and osteoclast (OC) formation were also controlled in mice treated with dendrimer. <h3>Conclusion</h3> Our data further argue in favor of strong anti-inflammatory and anti-OC properties of dendrimer ABP. Our data are also in favor of a possible oral administration of the compound.
Follicular lupus erythematosus: a new cutaneous manifestation of systemic lupus erythematosus
Authors: K. Morihara, S. Kishimoto, R. Shibagaki, H. Takenaka, H. Yasuno
Journal: British Journal of Dermatology (2002)

Summary We report the clinical, histopathological and immunological features of follicular erythema and petechiae in a 30‐year‐old Japanese woman with systemic lupus erythematosus (SLE). Histology showed this eruption to constitute a cutaneous manifestation of SLE. To our knowledge, this is the first reported case of follicular erythema and petechiae in association with SLE. Accordingly, we propose that this rare eruption be termed ‘follicular lupus erythematosus’.
Diurnal variation of power Doppler in metacarpophalangeal joints of patients with rheumatoid arthritis: a preliminary study
Authors: L. Semerano, M. Gutierrez, G. Falgarone, E. Filippucci, X. Guillot, M.-C. Boissier, W. Grassi
Journal: Annals of the Rheumatic Diseases (2011)

Power Doppler ultrasonography (PDUS) is a valid technique to detect, quantify and monitor synovial vascularisation in chronic inflammatory arthropathies.1,–,5 Despite this, its reliability is a major issue, and a consistent body of evidence emphasising the influence of several factors in PDUS variability has been published in the last few years.6,–,9 Thus, the minimisation of all potential sources of variability emerges as a crucial need.

Since in rheumatoid arthritis (RA) joint stiffness and pain show a clear circadian variation,10 we aimed at determining whether the PDUS signal of metacarpophalangeal (MCP) joints might vary according to the time of day in RA patients.

A total of 10 RA patients with active disease (DAS28 >3.2) despite disease-modifying antirheumatic drugs or biological treatment, recruited from the two rheumatology departments involved, underwent three PDUS examinations of MCP joints, during the same day, at three different times: T0, between 7:00 and 10:00; T1, 4–6 …
Arsenic Trioxide as an Inducer of Apoptosis and Loss of PML/RARα Protein in Acute Promyelocytic Leukemia Cells
Authors: Wenlin Shao, Mirco Fanelli, Fabiana F. Ferrara, Roberta Riccioni, Angelika Rosenauer, Kelly Davison, William W. Lamph, Samuel Waxman, Pier Giuseppe Pelicci, Francesco Lo Coco, Giuseppe Avvisati, Ugo Testy, Cesare Peschle, Carlo Gambacorti-Passerini, Clara Nervi, Wilson H. Miller
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Retinoids, which are derivatives of vitamin A, induce differentiation of acute promyelocytic leukemia (APL) cells in vitro and in patients.However, APL cells develop resistance to retinoic acid treatment.Arsenic trioxide (As 2 O 3 ) can induce clinical remission in patients with APL, including those who have relapsed after retinoic acid treatment, by inducing apoptosis (programmed cell death) of the leukemia cells.In this study, we investigated the molecular mechanisms by which As 2 O 3 induces apoptosis in retinoic acid-sensitive NB4 APL cells, in retinoic acid-resistant derivatives of these cells, and in fresh leukemia cells from patients.Methods: Apoptosis was assessed by means of DNA fragmentation analyses, TUNEL assays (i.e., deoxyuridine triphosphate labeling of DNA nicks with terminal deoxynucleotidyl transferase), and flow cytometry.Expression of the PML/RAR␣ fusion protein in leukemia cells was assessed by means of western blotting, ligand binding, and immunohistochemistry. Northern blotting and ribonuclease protection assays were used to evaluate changes in gene expression in response to retinoic acid and As 2 O 3 treatment.Results and Conclusions: As 2 O 3 induces apoptosis without differentiation in retinoic acid-sensitive and retinoic acidresistant APL cells at concentrations that are achievable in patients.As 2 O 3 induces loss of the PML/RAR␣ fusion protein in NB4 cells, in retinoic-acid resistant cells derived from them, in fresh APL cells from patients, and in non-APL cells transfected to express this protein.As 2 O 3 and retinoic acid induce different patterns of gene regulation, and they inhibit the phenotypes induced by each other.Understanding the molecular basis of these differences in the effects of As 2 O 3 and retinoic acid may guide the clinical use of arsenic compounds and provide insights into the management of leukemias that do not respond to retinoic acid.[
Modern Age Pathology of Pulmonary Arterial Hypertension
Authors: Elvira Stacher, Brian B. Graham, James M. Hunt, Aneta Gandjeva, Steve D. Groshong, Vallerie V. McLaughlin, Marsha Jessup, William E. Grizzle, Michaela A. Aldred, Carlyne D. Cool, Rubin M. Tuder
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown.Objectives: To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication.Methods: Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled.Measurements and Main Results: Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs.Conclusions: Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH.
Interferon-γ Release Assays and Tuberculin Skin Testing for Diagnosis of Latent Tuberculosis Infection in Healthcare Workers in the United States
Authors: Susan E. Dorman, Robert Belknap, Edward A. Graviss, Randall Reves, Neil Schluger, Paul Weinfurter, Yaping Wang, Wendy Cronin, Yael Hirsch-Moverman, Larry D. Teeter, Matthew Parker, Denise O. Garrett, Charles L. Daley
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs).Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs.A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011.A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later.Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.
Ventilation-perfusion inequality in chronic obstructive pulmonary disease.
Authors: P D Wagner, D R Dantzker, R Dueck, J L Clausen, J B West
Journal: Journal of Clinical Investigation (1977)

A multiple inert gas elimination method was used to study the mechanism of impaired gas exchange in 23 patients with advanced chronic obstructive pulmonary disease (COPD). Three patterns of ventilation-perfusion (Va/Q) inequality were found: (a) A pattern with considerable regions of high (greater than 3) VA/Q, none of low (less than 0.1) VA/Q, and essentially no shunt. Almost all patients with type A COPD showed this pattern, and it was also seen in some patients with type B. (b) A pattern with large amounts of low but almost none of high VA/Q, and essentially no shunt. This pattern was found in 4 of 12 type B patients and 1 of type A. (c) A pattern with both low and high VA/Q areas was found in the remaining 6 patients. Distributions with high VA/Q areas occurred mostly in patients with greatly increased compliance and may represent loss of blood-glow due to alveolar wall destruction. Similarly, well-defined modes of low VA/Q areas were seen mostly in patients with severe cough and sputum and may be due to reduced ventilation secondary to mechanical airways obstruction or distortion. There was little change in the VA/Q distributions on exercise or on breathing 100% O2. The observed patterns of VA/Q inequality and shunt accounted for all of the hypoxemia at rest and during exercise. There was therefore no evidence for hypoxemia caused by diffusion impairment. Patients with similar arterial blood gases often had dissimilar VA/Q patterns. As a consequence the pattern of VA/Q inequality could not necessarily be inferred from the arterial PO2 and PCO2.
Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene
Authors: F. Brasch, M. Griese, M. Tredano, G. Johnen, M. Ochs, C. Rieger, S. Mulugeta, K.M. Müller, M. Bahuau, M.F. Beers
Journal: European Respiratory Journal (2004)

Mutations in the surfactant protein C gene (SFTPC) were recently reported in patients with interstitial lung disease. In a 13-month-old infant with severe respiratory insufficiency, a lung biopsy elicited combined histological patterns of nonspecific interstitial pneumonia and pulmonary alveolar proteinosis. Immunohistochemical and biochemical analyses showed an intra-alveolar accumulation of surfactant protein (SP)-A, precursors of SP-B, mature SP-B, aberrantly processed proSP-C, as well as mono- and dimeric SP-C. Sequencing of genomic DNA detected a de novo heterozygous missense mutation of the SFTPC gene (g.1286T>C) resulting in a substitution of threonine for isoleucine (173T) in the C-terminal propeptide. At the ultrastructural level, abnormal transport vesicles were detected in type-II pneumocytes. Fusion proteins, consisting of enhanced green fluorescent protein and wild-type or mutant proSP-C, were used to evaluate protein trafficking in vitro. In contrast to wild-type proSP-C, mutant proSP-C was routed to early endosomes when transfected into A549 epithelial cells. In contrast to previously reported mutations, the 173T represents a new class of surfactant protein C gene mutations, which is marked by a distinct trafficking, processing, palmitoylation, and secretion of the mutant and wild-type surfactant protein C. This report heralds the emerging diversity of phenotypes associated with the expression of mutant surfactant C proteins.
Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response.
Authors: A Waage, A Halstensen, R Shalaby, P Brandtzaeg, P Kierulf, T Espevik
Journal: The Journal of Experimental Medicine (1989)

We examined the cerebrospinal fluid (CF) taken on admission from 60 patients with infections caused by Neisseria meningitidis for presence of TNF-alpha, IL-1, and IL-6. TNF-alpha was detected in CF in 55 and 19% (p = 0.03), IL-1 in 50 and 15% (p = 0.05), and IL-6 in 98 and 100% of patients with meningitis and septic shock/bacteremia, respectively. The median IL-6 concentration in CF in patients with meningitis was 154 ng/ml, and in patients with septic shock/bacteremia it was 42 ng/ml (p = 0.001). The level of LPS in CF correlated with the level of TNF-alpha (r = 0.91, p less than 0.001), but not with the level of IL-1 and IL-6. CF levels of TNF-alpha, IL-1, and IL-6 correlated with each other (r = 0.34-0.54, p less than 0.01), with the protein concentration (r = 0.34-0.62, p less than 0.01) and inversely with the CF/blood glucose ratio (r = -0.34 to -0.67, p less than 0.01). Only the Il-6 level correlated with the leukocyte count (r = 0.37, p less than 0.01). In rabbits TNF-alpha, IL-1, and IL-6 activities sequentially appeared in CF within 3 h of injection of meningococcal LPS or viable meningococci, whereas the main infiltration of granulocytes started after 4 h. TNF-alpha was detected in serum at concentrations less than 1/100 of those in CF after administration of LPS into the subarachnoid space, and conversely, TNF-alpha was detected in CF at concentrations 1/100 of those in serum after intravenous injection of LPS. The results demonstrate that TNF-alpha, IL-1, and IL-6 are sequentially produced in the initial phase of the local inflammatory response caused by meningococci, and that the subarachnoid space and systemic circulation are separate compartments with respect to production of TNF-alpha, IL-1, and IL-6.
A VARIANT OF TRICHOPHYTON RUBRUM ISOLATED IN HONG KONG
Authors: K. O. WONG, Y. F. CHAN
Journal: British Journal of Dermatology (1968)

SUMMARY.— A distinctive strain of Trichophyton rubrum has been isolated from 5 patients in Hong Kong. The infections caused by this strain were clinically more inflammatory and responded more rapidly to treatment than infections with the ordinary form of T. rubrum. The mycological characteristics of the Hong Kong strain are described in detail. It is possible that the Hong Kong and the Nigerian strains of T. rubrum are identical. The apparent differences are discussed; only further investigation will establish their significance.
Letter by Fisher and Johns Regarding Article, “Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease”
Authors: Matt Fisher, Tony Johns
Journal: Circulation (2007)

We read with great interest the recent review by Maree and Fitzgerald. 1 They should be congratulated for their informative summary of a quickly evolving area.However, we are concerned about their comments in the Aspirin Formulation section of the article.In this section, they cover the various formulations of aspirin and review findings from studies performed by their group.The authors caution the reader to be wary of enteric-coated formulations of aspirin because they have been observed to be less effective than plain aspirin tablets.It is unfortunate and concerning that they have chosen to generalize their observation instead of limiting their warnings to the specific products analyzed.All aspirin products and manufacturing practices are not the same.The original publication by the same authors demonstrated this in that they showed significant differences not only between plain aspirin and enteric-coated aspirin but also between different enteric-coated products over the same aspirin dose. 2 A recent clinical comparison of a leading entericcoated aspirin tablet and a plain aspirin tablet demonstrated no difference in the levels of platelet inhibition. 3General statements such as those regarding the efficacy of enteric-coated aspirin are frequently picked up by the lay media and may have a significant impact.There is already an underuse of aspirin in appropriate populations, and suggestions that enteric-coated formulations may not be effective could only negatively affect this situation.
Anakinra treatment in patients with adult-onset Still's disease is fast, effective, safe and steroid sparing: experience from an uncontrolled trial
Authors: G. D Kalliolias, P. E Georgiou, I. A Antonopoulos, A. P Andonopoulos, S.-N. C Liossis
Journal: Annals of the Rheumatic Diseases (2007)

Adult-onset Still’s disease (AOSD) is characterised by a group of clinical and laboratory findings indicating systemic inflammation.1 Recent data support the hypothesis that interleukin 1 is essential in mediating inflammation, particularly in recalcitrant AOSD.2,3

From December 2003 we treated 10 patients with AOSD diagnosed according to proposed criteria.4 Four of these 10 consecutive patients, 4 had refractory AOSD with persistently active disease, despite administration of high-dose steroids. Herein, we report that all four patients rapidly responded to administration of anakinra (100 mg/day) and were promptly weaned from high-dose steroids. Table 1 shows the patients’ demographics, …
Non-invasive ventilation for acute exacerbations of COPD: a new standard of care
Authors: L. BROCHARD
Journal: Thorax (2000)

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a frequent cause of admission to hospital and the intensive care unit (ICU). During these episodes a major deterioration in gas exchange is accompanied by a worsening in the clinical condition of the patient, characterised by a rapid and shallow breathing pattern, severe dyspnoea, right ventricular failure, and encephalopathy. The pathophysiological pathway of all these features is the inability of the respiratory system to maintain adequate alveolar ventilation in the presence of major abnormalities in respiratory mechanics. Hypercapnia, acidosis, and hypoxaemia all ensue, leading to clinical deterioration in cardiovascular and neurological functions. What triggers the abnormal breathing pattern of the patient is still unclear. Although it has been suggested that rapid shallow breathing may afford a protection against the development of respiratory muscle fatigue, this notion has been challenged by studies of weaning off mechanical ventilation where the occurrence of acute respiratory failure can be closely monitored and analysed.1 2 The key element during decompensation seems to be the shortening of the inspiratory time, inducing both a decrease in tidal volume and an increase in respiratory frequency. Because this is associated with, or is secondary to, excessive respiratory loads, treatment should be directed at reducing the loads imposed on the respiratory muscles. Unfortunately, the ability of medical treatment to reverse severe respiratory failure in these patients is limited. When hypoventilation becomes so severe that several organ dysfunctions occur, there is no choice other than to provide “artificial” ventilation to avoid a fatal outcome. The traditional way has been to use endotracheal intubation as a means of access to the lower airways and to deliver ventilation to the patient's lungs. A more recent approach, called non-invasive ventilation (NIV), has profoundly changed the management and outcome of these patients.3 4 

Three …
Barrett's oesophagus: from metaplasia to dysplasia and cancer
Authors: J-F Flejou
Journal: Gut (2005)

Barrett's oesophagus is a premalignant condition that predisposes to the development of oesophageal adenocarcinoma. It is detected on endoscopy and confirmed histologically by the presence in the lower oesophagus of a metaplastic mucosa, the so-called specialised epithelium, which resembles incomplete intestinal metaplasia in the stomach. These similarities with incomplete intestinal metaplasia are present on histology, mucin histochemistry, and immunohistochemistry with various differentiation markers (cytokeratins and MUC antigens). On morphology, the carcinogenetic process of Barrett's mucosa progresses through increasing grades of epithelial dysplasia. Dysplasia, a synonym of intraepithelial neoplasia, is the only marker that can be used at the present time to delineate a population of patients at high risk of cancer. Among the numerous molecular events that have been shown to play a role in the neoplastic transformation of Barrett's mucosa, only changes in DNA ploidy, increased proliferation, and alterations of the p53 gene have been suggested to be of potential help in the surveillance of patients.
Distinct neurological disorders with ATP1A3 mutations
Authors: Erin L Heinzen, Alexis Arzimanoglou, Allison Brashear, Steven J Clapcote, Fiorella Gurrieri, David B Goldstein, Sigurður H Jóhannesson, Mohamad A Mikati, Brian Neville, Sophie Nicole, Laurie J Ozelius, Hanne Poulsen, Tsveta Schyns, Kathleen J Sweadner, Arn van den Maagdenberg, Bente Vilsen
Journal: The Lancet Neurology (2014)