tbuckley/cabot-search huggingface dataset:
Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study
Authors: Elisa Gremese, Fausto Salaffi, Silvia Laura Bosello, Alessandro Ciapetti, Francesca Bobbio-Pallavicini, Roberto Caporali, Gianfranco Ferraccioli
Journal: Annals of the Rheumatic Diseases (2012)

Background To assess whether, in the real world of three early arthritis clinics, early referral could allow the best outcome, ie, remission, to be reached, and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa. Methods 1795 patients with early arthritis (symptom duration ≤12 months) were entered into a prospective follow-up study. 711 patients (39.6%) were diagnosed with rheumatoid arthritis (RA). Each RA patient was treated according to the local algorithm, in three tertiary referral centres (representing a small province, a medium sized province and a metropolitan area, respectively). Remission, defined using the disease activity score in 28 joints (DAS28 &lt;2.6) and American College of Rheumatology (ACR) criteria, was the major outcome evaluated at the 12-month follow-up. Results DAS28 remission was achieved in 34.3% (range 19.5–49%) of RA patients and ACR remission in 15.2% (range 8.5–20.6%). At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome: being in very early rheumatoid arthritis (VERA; less than 12 weeks symptom duration at the time of first treatment) and being on disease-modifying antirheumatic drugs (DMARD) within 3 months from disease onset. Among RA patients in remission, only 10% of VERA subjects received an anti-TNF blocker compared with 32.2% of non-VERA patients (p=0.002, OR 0.23, 95% CI 0.09 to 0.64). Conclusions In a real-world setting, the 12 weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome, ie, remission of RA. Moreover, VERA represents a window of opportunity in terms of cost saving.
Empirical constraints for perceptual modeling
Authors: Charles R. Fox
Journal: Behavioral and Brain Sciences (2003)

This new heuristic model of perceptual analysis raises interesting issues but in the end falls short. Its arguments are more in the Cartesian than Gestalt tradition. Much of the argument is based on setting up theoretical straw men and ignores well known perceptual and brain science. Arguments are reviewed in light of known physiology and traditional Gestalt theory.
Radon therapy ameliorates disease progression and prolongs survival in TNF α tg mice
Authors: Matthias Pauthner, Christina Janko, Wolfgang Baum, Christine Schorn, Heidemarie Dobias, Angelika Moder, Georg Schett, Martin Herrmann
Journal: Annals of the Rheumatic Diseases (2012)

Leukotrienes generated by 5-lipoxygenase (5-LOX)–catalyzed reaction are key regulators of inflammation. In ionophore-stimulated (A23187; 1–2.5 μM) human blood neutrophils or differentiated HL-60 cells, vitamin E forms differentially inhibited leukotriene B<sub>4</sub> (LTB<sub>4</sub>) with an IC<sub>50</sub> of 5–20 μM for γ-tocopherol, δ-tocopherol (δT), and γ-tocotrienol, but a much higher IC<sub>50</sub> for α-tocopherol. 13′-Carboxychromanol, a long-chain metabolite of δT, suppressed neutrophil- and HL-60 cell-generated LTB<sub>4</sub> with an IC<sub>50</sub> of 4–7 μM and potently inhibited human recombinant 5-LOX activity with an IC<sub>50</sub> of 0.5–1 μM. In contrast, vitamin E forms had no effect on human 5-LOX activity but impaired ionophore-induced intracellular calcium increase and calcium influx as well as the subsequent signaling including ERK1/2 phosphorylation and 5-LOX translocation from cytosol to the nucleus, a key event for 5-LOX activation. Further investigation showed that δT suppressed cytosolic Ca<sup>2+</sup> increase and/or LTB<sub>4</sub> formation triggered by ionophores, sphingosine 1-phosphate, and lysophosphatidic acid but not by fMLP or thapsigargin, whereas 13′-carboxychromanol decreased cellular production of LTB<sub>4</sub> regardless of different stimuli, consistent with its strong inhibition of the 5-LOX activity. These observations suggest that δT does not likely affect fMLP receptor-mediated signaling or store depletion-induced calcium entry. Instead, we found that δT prevented ionophore-caused cytoplasmic membrane disruption, which may account for its blocking of calcium influx. These activities by vitamin E forms and long-chain carboxychromanol provide potential molecular bases for the differential anti-inflammatory effects of vitamin E forms in vivo.
Increasing Peritoneal Contact Area During Dialysis Improves Mass Transfer
Authors: MICHAEL F. FLESSNER, JOANNE LOFTHOUSE, ANGELA WILLIAMS
Journal: Journal of the American Society of Nephrology (2001)

Previous studies in mice demonstrated that relatively large volumes in the peritoneal cavity made contact with only 40% of the anatomic peritoneum and that this contact area (Acontact) could be increased with use of a surfactant, dioctyl sodium sulfosuccinate (DSS). To investigate the hypothesis that mass transfer rates during peritoneal dialysis are dependent on the area of peritoneum in contact with the dialysis solution, rats were dialyzed for 2 h with a solution that contained 14C-mannitol, with or without 0.02% DSS. The mass transfer-area coefficients (MTAC) were determined to be (mean ± SEM, ml/min): no DSS, 0.163 ± 0.008; with DSS, 0.247 ± 0.006 (P < 0.002). DSS also caused an increase in total protein loss over 2 h (mean ± SEM, mg): no DSS, 83.8 ± 15.8; DSS, 159.5 ± 6.3 (P < 0.001). In a separate set of animals, the ratio (R) of Acontact to anatomic area in each plane was measured as in the previous study Rmean (mean ± SEM) and equaled 0.466 ± 0.075, no DSS; 0.837 ± 0.074, with DSS. The ratio of MTAC (1.52) and protein loss (1.90) approximate the ratio of Rmeans (1.78). Because MTAC = mass transfer coefficient (MTC) × Acontact, small peritoneal transport chambers were used to determine MTC for 14C-mannitol and fluorescein isothiocyanate-albumin. MTCmannitol did not change significantly with the addition of DSS. MTCalnbumin (cm/min × 104, mean ± SEM) equaled 1.47 ± 0.45 without DSS and 1.78 ± 0.52 with DSS (P < 0.04). It was concluded that DSS increases the mass transfer rates of mannitol and protein by increasing Acontact, whereas protein transport is further augmented by an apparent increase in the barrier permeability to protein.
IMMUNITY IN INTESTINAL OBSTRUCTION
Authors: Carl A. Dragstedt, James J. Moorhead
Journal: The Journal of Experimental Medicine (1918)

1. There is no increased immunity or tolerance to intestinal obstruction after recovery from previous obstruction. 2. Dogs recovered from intestinal obstruction are not more resistant to injections of closed loop fluid than normal dogs. 3. Dogs injected with closed loop fluid are not more resistant to intestinal obstruction than normal dogs. 4. In dogs the normal variation in resistance both to intestinal obstruction and to the injection of closed loop fluid is large.
Let's forget the everyday/laboratory controversy
Authors: Lia Kvavilashvili, Judi Ellis
Journal: Behavioral and Brain Sciences (1996)

Abstract In contrast to its aims, Koriat &amp; Goldsmith&amp;apos;s article vividly demonstrates(1) the complementarity of ecological and traditional approaches and (2) the difficulty of characterising the growing diversity of memory research with a single set of distinctions. Moreover, the contrast between correspondence and storehouse metaphors is important enough to stand alone without reference to an everyday/laboratory controversy, which is neither acute nor necessary.
Down-regulation of Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 Expression by Soy Isoflavones Enhances Prostate Cancer Radiotherapy <i>In vitro</i> and <i>In vivo</i>
Authors: Julian J. Raffoul, Sanjeev Banerjee, Vinita Singh-Gupta, Zvi E. Knoll, Alemu Fite, Hao Zhang, Judith Abrams, Fazlul H. Sarkar, Gilda G. Hillman
Journal: Cancer Research (2007)

We previously showed that genistein, the major bioactive component of soy isoflavones, acts as a radiosensitizer and potentiates prostate tumor cell killing by radiation in vitro and in animal tumor models in vivo. However, when given alone in vivo, pure genistein promoted increased lymph node metastasis, which was not observed with a soy isoflavone mixture consisting of genistein, daidzein, and glycitein. In this study, we show that soy inhibit tumor cell growth and potentiates radiation-induced cell killing in vitro like pure genistein. In an orthotopic model, combining soy isoflavones with tumor irradiation inhibited prostate tumor growth. To determine the molecular mechanisms by which soy isoflavones potentiate radiotherapy, we investigated apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) and nuclear factor kappaB (NF-kappaB), two signaling molecules involved in survival pathways. Soy isoflavones decreased APE1/Ref-1 expression in vitro, whereas radiation up-regulated it. Pretreatment with soy isoflavones followed by radiation inhibited APE1/Ref-1 expression. APE1/Ref-1 decrease correlated with decreased DNA-binding activity of NF-kappaB mediated by soy isoflavones and radiation, thus promoting cell killing. In vivo treatment of prostate tumors with soy isoflavones and radiation down-regulated APE1/Ref-1 protein expression and NF-kappaB activity, confirming the molecular alterations observed in vitro. The down-regulation of APE1/Ref-1 and NF-kappaB by isoflavones, in vitro and in vivo, supports our hypothesis that these markers represent biological targets of isoflavones. Indeed, a 2-fold increase in APE1/Ref-1 expression, obtained by cDNA transfection, resulted in a 2-fold increase in NF-kappaB DNA-binding activity, and both of which were down-regulated by soy isoflavones, confirming the cross-talk between these molecules and, in turn, causing radiosensitization.
Characterization of anion exchangers in an inner medullary collecting duct cell line.
Authors: G Obrador, H Yuan, T M Shih, Y H Wang, M A Shia, E A Alexander, J H Schwartz
Journal: Journal of the American Society of Nephrology (1998)

Although the inner medullary collecting duct (IMCD) plays a major role in urinary acidification, the molecular identification of many of the specific components of the transport system in this nephron segment are lacking. A cultured line of rat IMCD cells was used to characterize the mediators of cellular HCO3 exit. This cell line functionally resembles alpha-intercalated cells. Physiologic experiments document that HCO3- transport is a reversible, electroneutral, Cl dependent, Na+-independent process. It can be driven by Cl-gradients and inhibited by stilbenes such as 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid. Immunohistochemical analysis, using a rabbit polyclonal antibody against the carboxy-terminal 12 amino acids of anion exchanger 1 (AE1), revealed a distribution of immunoreactive protein that is consistent with a basolateral localization of AE in cultured cells and in alpha-intercalated cells identified in sections of rat kidney cortex. Immunoblot revealed two immunoreactive bands (approximately 100 and 180 kD in size) in membranes from cultured IMCD cells, rat renal medulla, and freshly isolated IMCD cells. The mobility of the lower molecular weight band was similar to that of AE1 in red blood cell ghosts and kidney homogenate and therefore probably represents AE1. The mobility of the 180-kD band is similar to that for rat stomach and kidney AE2 and therefore probably represents AE2. Selective biotinylation of the apical or basolateral membrane proteins in cultured IMCD cells revealed that both AE1 and AE2 are polarized to the basolateral membrane. Northern blot analysis documented the expression of mRNA for AE1 and AE2 but not AE3. Furthermore, the cDNA sequence of AE1 and AE2 expressed by these cells was found to be virtually identical to that reported for kidney AE1 and rat stomach AE2. It is concluded that this cultured line of rat IMCD cells expresses two members of the anion exchanger gene family, AE1 and AE2, and both of these exchangers probably mediate the electroneutral Cl--dependent HCO3-transport observed in this cell line.
P19 Worrying Trend Of Labelling Ambiguous Deaths As Pneumonia And Potential Impact On Respiratory Service In A District General Hospital
Authors: EL Tan, E Davies, S Javed, R Sundar, I Aziz
Journal: Thorax (2013)

<h3>Background</h3> Pneumonia is a common cause of death recorded on death certificates. This data is used by Dr Foster to calculate hospital specific mortality rate (HSMR). However there is a general impression that pneumonia is recorded as the cause of death without confirmation. The British Thoracic Society (BTS) defines pneumonia as ‘symptoms and signs consistent with an acute lower respiratory tract infection associated with new radiographic shadowing for which there is no other explanation’ <h3>Aims </h3> Our aim was to establish if patients reported to have died of pneumonia had radiographic shadowing in accordance with the BTS definition and if they have been managed with appropriate antibiotics as per BTS guidelines <sup>1</sup>. <h3>Methods </h3> We reviewed the case notes and chest x-rays (CXR) of 111 consecutive patients where pneumonia was stated as the cause of the death. We also investigated whether correct antibiotic therapy was used as per hospital guidelines. <h3>Results </h3> 111 patients (53 male, mean age 80.6) were given diagnosis of pneumonia on their death certificates as follows; aspiration pneumonia 20 patients, bronchopneumonia 8 patients, community acquired pneumonia 19 patients, pneumonia 44 patients and hospital acquired pneumonia 20 patients. Out of these 111 patients, 75 (67.6%) patients had radiological changes consistent with a diagnosis of pneumonia on CXR. Out of these 75 patients with radiologically confirmed pneumonia 29 (38.7%) were given incorrect antibiotics as they were treated mainly for sepsis. <h3>Conclusions </h3> Our findings show a very worrying trend of incorrectly recording pneumonia as cause of death in a third of patients, who were given pneumonia as cause of death. This would increase the HSMR for pneumonia as calculated by Dr Foster. In our opinion pneumonia as a cause of death is an easy option for many medical practitioners. <h3>Recommendations </h3> We recommend an early input by respiratory physicians for all respiratory admisssions to make sure that respiratory illnesses are managed correctly. <h3>References</h3> <i>Thorax</i> 2009; 64 (Supplement III) : 1–61.
Uniformity of dissecting microscope appearances in proximal small intestine
Authors: J. A. Walker-Smith
Journal: Gut (1972)

The uniformity of mucosal morphology within the distal duodenum and the first loop of jejunum, ie, the area usually biopsied, was examined at necropsy in 116 children. In those with no evidence of gastrointestinal disease there was no significant variation within this area, but in 25 children with mucosal abnormality, variation occurred within a small area. The crests of the plicae circulares were more often more severely abnormal than the area in the valleys between. Owing to the small size of biopsy specimens, it is apparent from this study that such specimens may not be representative of the proximal small intestinal mucosa in children suffering from the disorders of the small intestine encountered in this study.
Bortezomib With or Without Dexamethasone in Primary Systemic (Light Chain) Amyloidosis
Authors: Efstathios Kastritis, Ashutosh D. Wechalekar, Meletios A. Dimopoulos, Giampaolo Merlini, Philip N. Hawkins, Vittorio Perfetti, Julian D. Gillmore, Giovanni Palladini
Journal: Journal of Clinical Oncology (2010)

PURPOSE To assess the efficacy and tolerability of bortezomib with or without dexamethasone and to define prognostic factors for patients with primary systemic light chain (AL) amyloidosis treated with bortezomib or both. PATIENTS AND METHODS Ninety-four patients from three centers were analyzed: 19% received the combination as first-line treatment, 81% had a median of two previous therapies, and 69% had refractory disease, while most patients had symptomatic heart involvement or elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Results A hematologic response was achieved in 71% within a median of 52 days, including 25% complete responses (CRs). Previously untreated patients had a 47% CR rate. Age 65 years or younger (P = .043) and twice weekly administration of bortezomib (P = .041) were associated with higher response rates. A cardiac response was documented in 29% of patients, in most as sustained improvement of functional class and less often as a decrease in wall thickness. Hematologic responses were associated with a cardiac response and NT-proBNP reduction. After a median follow-up of 12 months, 29% of patients had organ progression and 27% had hematologic progression. Median survival has not been reached and the 1-year survival rate is 76%. Baseline NT-proBNP was independently associated with survival (P = .001), while in a landmark analysis, survival was associated with NT-proBNP reduction of > or = 30% (P = .006) and achievement of hematologic response (P = .001). Toxicity was manageable and mostly consisted of neuropathy, orthostasis, peripheral edema, and constipation or diarrhea. CONCLUSION Bortezomib with or without dexamethasone is active in AL amyloidosis and induces rapid responses and high rates of hematologic and organ responses. Serial measurement of cardiac biomarkers is a powerful predictor of outcome.
Reduction and Cessation of Cigarette Smoking and Risk of Cancer: A Cohort Study of Korean Men
Authors: Yun-Mi Song, Joohon Sung, Hong-Jun Cho
Journal: Journal of Clinical Oncology (2008)

Purpose Reducing cigarette smoking has been proposed as a method of harm reduction. The effect of smoking reduction on cancer risk has not been studied in Asian populations. Patients and Methods A total of 479,156 Korean men, age 30 to 58 years, were stratified into nine groups based on smoking status in 1990 and 1992. From 1992 to 2003, patients were observed and tested for the occurrence of cancer. Results There was no association between smoking reduction and risk of all cancers. However, the risk of smoking-related cancers tended to decrease, though not significantly, when heavy smokers (≥ 20 cigarettes/d) became moderate smokers (10 to 19 cigarettes/d), with a hazard ratio (HR) of 0.91 (95% CI, 0.82 to 1.02). For lung cancer, patients who reduced from heavy to moderate smoking and from heavy to light smoking (&lt; 10 cigarettes/d) had significantly decreased risks based on multivariable-adjusted HRs (HR = 0.72, 95% CI, 0.49 to 0.89; HR = 0.63, 95% CI, 0.46 to 0.84, respectively). Study participants who never smoked, sustained ex-smokers, and quitters had lower risks for all cancers, smoking-related cancers, and lung cancer in a dose-response manner as compared with heavy smokers. Conclusion Smoking reduction was associated with a significant decrease in the risk of lung cancer, but the size of risk reduction was disproportionately smaller than that expected from the reduced amount of cigarette consumption. Although smoking cessation should be the cornerstone of preventing smoking-related cancers, smoking reduction could be considered as a strategy to supplement smoking cessation for those who are unable to quit smoking immediately.
Conflicting findings on effectiveness of low level laser therapy for tendinopathy
Authors: Daniel Steffens, Chris G Maher
Journal: British Journal of Sports Medicine (2011)

▶ 1. Tumilty S, 2. Munn J, 3. McDonough S, 4. et al . Photomed Laser Surg 2010;28:3–16. [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Low level laser therapy (LLLT) has a long history of use in the management of soft tissue injuries and inflammation. Its effectiveness in the management of tendinopathy is not yet established. To establish the effectiveness of LLLT in the treatment of tendinopathy and any effect of LLLT dosage on study outcomes. Eight key biomedical databases were searched for randomised controlled trials published up to August 2008. Eligible trials had to compare LLLT as a single modality with placebo, no treatment or other treatments, and measure pain or function outcomes. Independent reviewers applied the selection criteria, assessed study quality using the 0–10 PEDro scale, and extracted study … [1]: {openurl}?query=rft.jtitle%253DPhotomedicine%2Band%2Blaser%2Bsurgery%26rft.stitle%253DPhotomed%2BLaser%2BSurg%26rft.aulast%253DTumilty%26rft.auinit1%253DS.%26rft.volume%253D28%26rft.issue%253D1%26rft.spage%253D3%26rft.epage%253D16%26rft.atitle%253DLow%2Blevel%2Blaser%2Btreatment%2Bof%2Btendinopathy%253A%2Ba%2Bsystematic%2Breview%2Bwith%2Bmeta-analysis.%26rft_id%253Dinfo%253Adoi%252F10.1089%252Fpho.2008.2470%26rft_id%253Dinfo%253Apmid%252F19708800%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1089/pho.2008.2470&link_type=DOI [3]: /lookup/external-ref?access_num=19708800&link_type=MED&atom=%2Fbjsports%2F45%2F5%2F459.atom [4]: /lookup/external-ref?access_num=000274597500002&link_type=ISI
Development of Cardiomyopathy in Female Carriers of Duchenne and Becker Muscular Dystrophies
Authors: L Politano, V Nigro, G Nigro, V R Petretta, L Passamano, S Papparella, S Di Somma, L I Comi
Journal: JAMA (1996)

To characterize the presence and behavior of the dystrophinopathic myocardial damage in female carriers of a gene defect at the Xp21 locus of the X chromosome that causes Duchenne and Becker muscular dystrophies (DMD and BMD).Cohort study from April 1, 1985, to April 30, 1995, with cardiologic follow-up performed yearly for a minimum of 3 to a maximum of 10 years.Counseling center for genetic muscular disorders.A total of 197 women and girls aged 5 to 60 years ascertained to be carriers of the DMD (n = 152) or BMD (n = 45) gene.Cardiac status at yearly examinations as determined by 12-lead electrocardiogram (ECG), 24-hour ambulatory ECG, M-mode and 2-dimensional echocardiography, and carotid pulse tracing. Myocardial scintigram was performed on each individual at least twice during the study. Immunohistochemical analysis of dystrophin from myocardium and/or skeletal muscle biopsy was performed in 12 carriers.Preclinical or clinically evident myocardial involvement was found in 166 cases (84.3%), without significant differences in percentage and behavior between DMD and BMD carriers. Its occurrence increased significantly with age, from 54.5% (18 cases) in carriers aged between 5 and 16 years to 90.2% (148 cases) in carriers older than 16 years. Dystrophin anomalies were detected at the membrane level of the myocardial fibers in all endomyocardial biopsy specimens.Genetic anomalies can be considered the primary cause of myocardial damage in carriers of dystrophinopathic myopathies; myocardial damage shows the same behavior already described in DMD and BMD patients and progresses from preclinical to dilated cardiomyopathy, passing through stages of myocardial hypertrophy or dysrhythmias.