tbuckley/cabot-search huggingface dataset:
STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMONIA DUE TO FRIEDLÄDER'S BACILLUS
Authors: Mary Ruth Smith, W. Barry Wood
Journal: The Journal of Experimental Medicine (1947)

Phagocytosis of encapsulated Friedländer's bacilli has been demonstrated in the lungs of rats in the absence of both circulating and local antibody. The mechanism of phagocytosis independent of antibody has been shown to be due to the same surface factors that operate in the phagocytosis of Type I pneumococcus under similar conditions. Direct observation of the phagocytic process reveals that leucocytes in the lung can phagocyte unopsonized Friedländer's bacilli only by trapping them against the surfaces of alveolar walls or bronchi, or by pinning them against the surfaces of adjacent leucocytes. Evidence is presented that Friedländer's bacilli thus phagocyted are rapidly killed in the cytoplasm of the phagocytic cells. Reasons are discussed for the failure of prolonged chemotherapy to cure lung abscesses that not infrequently complicate the pneumonia due to Friedländer's bacillus.
Analysis of Observational Studies in the Presence of Treatment Selection Bias
Authors: Thérèse A. Stukel, Elliott S. Fisher, David E. Wennberg, David A. Alter, Daniel J. Gottlieb, Marian J. Vermeulen
Journal: JAMA (2007)

Comparisons of outcomes between patients treated and untreated in observational studies may be biased due to differences in patient prognosis between groups, often because of unobserved treatment selection biases.To compare 4 analytic methods for removing the effects of selection bias in observational studies: multivariable model risk adjustment, propensity score risk adjustment, propensity-based matching, and instrumental variable analysis.A national cohort of 122,124 patients who were elderly (aged 65-84 years), receiving Medicare, and hospitalized with acute myocardial infarction (AMI) in 1994-1995, and who were eligible for cardiac catheterization. Baseline chart reviews were taken from the Cooperative Cardiovascular Project and linked to Medicare health administrative data to provide a rich set of prognostic variables. Patients were followed up for 7 years through December 31, 2001, to assess the association between long-term survival and cardiac catheterization within 30 days of hospital admission.Risk-adjusted relative mortality rate using each of the analytic methods.Patients who received cardiac catheterization (n = 73 238) were younger and had lower AMI severity than those who did not. After adjustment for prognostic factors by using standard statistical risk-adjustment methods, cardiac catheterization was associated with a 50% relative decrease in mortality (for multivariable model risk adjustment: adjusted relative risk [RR], 0.51; 95% confidence interval [CI], 0.50-0.52; for propensity score risk adjustment: adjusted RR, 0.54; 95% CI, 0.53-0.55; and for propensity-based matching: adjusted RR, 0.54; 95% CI, 0.52-0.56). Using regional catheterization rate as an instrument, instrumental variable analysis showed a 16% relative decrease in mortality (adjusted RR, 0.84; 95% CI, 0.79-0.90). The survival benefits of routine invasive care from randomized clinical trials are between 8% and 21%.Estimates of the observational association of cardiac catheterization with long-term AMI mortality are highly sensitive to analytic method. All standard risk-adjustment methods have the same limitations regarding removal of unmeasured treatment selection biases. Compared with standard modeling, instrumental variable analysis may produce less biased estimates of treatment effects, but is more suited to answering policy questions than specific clinical questions.
Negative expiratory pressure technique correlates with the measurements of upper airway collapsibility (UAC) during sleep in children
Authors: Helena Larramona Carrera, Joseph M. McDonough, Joan Carles Oliva, Paul R. Gallagher, Jingtao Huang, Carole Marcus
Journal: European Respiratory Journal (2014)

The gold standard to measure UAC in children is the slope of pressure-flow (SPF) while applying a nasal pressure (PN).Studies have shown differences between controls and OSAS when it is applied a negative pressure in expiration (NEP) during wakefulness.Hypothesis: there is a relationship between NEP technique and SPF. We also evaluate differences in seated and supine. Methods: Controls (AHI [≤ 1.5/h) and OSAS (AHI ≥ 5/h). During wakefulness, NEP in sitting/supine was applied during 1st second of expiration. UA muscle activity was measured using intra-oral electrodes. The ratio of the area under the expiratory flow-volume curve during NEP compared to tidal breathing (RatioNEP) was calculated. Integrated EMG moving average area under the curve during NEP/basal was measured (RatioEMG). Both groups underwent pressure-flow measurements during sleep while wearing same intraoral electrodes.Two techniques were applied to decrease PN to subatmospheric, resulting in an activated and relatively hypotonic UA. The SPF in each states was correlated with RatioNEP in both positions (ANOVA). Results: 20 controls; 7 OSAS. In seated position we found an inverse relationship between RatioNEP and SPF in states hypotonic and active with respectively coefficient -8.9 and -12.1 (p
Curcumin Extract for Prevention of Type 2 Diabetes
Authors: Somlak Chuengsamarn, Suthee Rattanamongkolgul, Rataya Luechapudiporn, Chada Phisalaphong, Siwanon Jirawatnotai
Journal: Diabetes Care (2012)

OBJECTIVE To assess the efficacy of curcumin in delaying development of type 2 diabetes mellitus (T2DM) in the prediabetic population. RESEARCH DESIGN AND METHODS This randomized, double-blinded, placebo- controlled trial included subjects (n = 240) with criteria of prediabetes. All subjects were randomly assigned to receive either curcumin or placebo capsules for 9 months. To assess the T2DM progression after curcumin treatments and to determine the number of subjects progressing to T2DM, changes in β-cell functions (homeostasis model assessment [HOMA]-β, C-peptide, and proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin), and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the course of intervention. RESULTS After 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (61.58 vs. 48.72; P &amp;lt; 0.01) and lower C-peptide (1.7 vs. 2.17; P &amp;lt; 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P &amp;lt; 0.001) and higher adiponectin (22.46 vs. 18.45; P &amp;lt; 0.05) when compared with the placebo group. CONCLUSIONS A 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of β-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial.
Decreased VEGF concentration in lung tissue and vascular injury during ARDS
Authors: Y. Abadie, F. Bregeon, L. Papazian, F. Lange, B. Chailley-Heu, P. Thomas, P. Duvaldestin, S. Adnot, B. Maitre, C. Delclaux
Journal: European Respiratory Journal (2005)

Endothelial injury is an important prognostic factor in acute respiratory distress syndrome (ARDS). Decreased production of vascular endothelial growth factor (VEGF) in ARDS may favour vascular lesions, since VEGF promotes endothelial survival by inhibiting apoptosis. This study sought to document low VEGF levels in lung tissue from ARDS patients, to determine whether the cause was injury to alveolar type II cells (the main pulmonary source of VEGF) and to evaluate the vascular consequences. Lung specimens were obtained by open biopsy or autopsy from 29 patients with severe ARDS (two survivors) and five controls. As compared with controls, homogenates of lung tissue from ARDS patients contained less VEGF (median (interquartile range) ARDS 8.2 (4.7–12.2) versus controls 28.4 (9.9–47.1) ng·g −1 protein). Increased immunostaining with surfactant protein B was seen in ARDS lungs. Extensive cellular apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling staining), including endothelial and alveolar type II cells, was demonstrated, and vascular bed density (CD31 immunostaining) decreased in ARDS lungs as compared with controls. VEGF levels were negatively correlated to apoptotic endothelial cell counts. In conclusion, decreased vascular endothelial growth factor levels in lung tissue may participate in the decrease in lung perfusion in acute respiratory distress syndrome.
A Phase I Study of Eribulin Mesylate (E7389), a Mechanistically Novel Inhibitor of Microtubule Dynamics, in Patients with Advanced Solid Malignancies
Authors: Sanjay Goel, Alain C. Mita, Monica Mita, Eric K. Rowinsky, Quincy S. Chu, Nancy Wong, Christopher Desjardins, Fang Fang, Mendel Jansen, Dale E. Shuster, Sridhar Mani, Chris H. Takimoto
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Eribulin mesylate (E7389), a non-taxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analogue of halichondrin B that acts via a mechanism distinct from conventional tubulin-targeted agents. This phase I study determined the maximum tolerated dose (MTD) and pharmacokinetics of eribulin administered on a 3 of 4 week schedule in patients with advanced solid malignancies. Experimental Design: Patients received eribulin mesylate (1-hour i.v. infusion) on days 1, 8, and 15 of a 28-day cycle. Dosing began at 0.25 mg/m2 with escalation guided by dose-limiting toxicities (DLT). MTD, DLTs, safety, pharmacokinetics, and antitumor activity were characterized. Results: Thirty-two patients received eribulin mesylate (0.25, 0.5, 0.7, 1.0, or 1.4 mg/m2). Neutropenia was the principal DLT: At 1.4 mg/m2, two patients experienced grade 4 neutropenia, one of whom also developed grade 3 fatigue; three additional patients experienced grade 3 neutropenia and were not treated during cycle 1 on day 15. Therefore, the MTD was 1.0 mg/m2. Fatigue (53% overall, 13% grade 3, no grade 4), nausea (41%, all grade 1/2), and anorexia (38% overall, 3% grade 3, no grade 4) were the most common eribulin-related adverse events. Eight patients reported grade 1/2 neuropathy (no grade 3/4). Eribulin pharmacokinetics were dose-proportional over the dose range studied. One patient (cervical cancer) achieved an unconfirmed partial response lasting 79 days. Ten patients reported stable disease. Conclusions: Eribulin mesylate, given on days 1, 8, and 15 of a 28-day cycle, exhibits manageable tolerability at 1.0 mg/m2 with further dose escalation limited by neutropenia and fatigue.
The Dock and Lock Method: A Novel Platform Technology for Building Multivalent, Multifunctional Structures of Defined Composition with Retained Bioactivity
Authors: Chien-Hsing Chang, Edmund A. Rossi, David M. Goldenberg
Journal: Clinical Cancer Research (2007)

Abstract The idea, approach, and proof-of-concept of the dock and lock (DNL) method, which has the potential for making a large number of bioactive molecules with multivalency and multifunctionality, are reviewed. The key to the DNL method seems to be the judicious application of a pair of distinct protein domains that are involved in the natural association between protein kinase A (PKA; cyclic AMP–dependent protein kinase) and A-kinase anchoring proteins. In essence, the dimerization and docking domain found in the regulatory subunit of PKA and the anchoring domain of an interactive A-kinase anchoring protein are each attached to a biological entity, and the resulting derivatives, when combined, readily form a stably tethered complex of a defined composition that fully retains the functions of individual constituents. Initial validation of the DNL method was provided by the successful generation of several trivalent bispecific binding proteins, each consisting of two identical Fab fragments linked site-specifically to a different Fab. The integration of genetic engineering and conjugation chemistry achieved with the DNL method may not only enable the creation of novel human therapeutics but could also provide the promise and challenge for the construction of improved recombinant products over those currently commercialized, including cytokines, vaccines, and monoclonal antibodies.
Age-associated changes in electrophysiologic remodeling: a potential contributor to initiation of atrial fibrillation
Authors: E ANYUKHOVSKY, E SOSUNOV, P CHANDRA, T ROSEN, P BOYDEN, P DANILOJR, M ROSEN
Journal: Cardiovascular Research (2004)

Although the incidence of atrial fibrillation (AF) increases with age, the cellular electrophysiological changes that render the atria of aged individuals more susceptible to AF remain poorly understood. We hypothesized that dispersion of atrial repolarization increases with aging, creating a substrate for initiation of AF.Four groups of dogs were studied: adult and old dogs in normal sinus rhythm (SR) and adult and old dogs with chronic AF (CAF) induced by rapid atrial pacing. In each dog, action potentials (AP) were recorded with microelectrodes from isolated endocardial preparations of four regions of right atrium and three regions of left atrium. Two indices of AP duration (APD) heterogeneity were obtained in each dog by calculating standard deviation (SD) and the coefficient of variation (COV=[SD/mean] x 100%).In SR groups, APD averaged across all regions was significantly longer in old than in adult tissues. Both indices of APD heterogeneity were higher in old dogs in comparison to adult. At both ages, CAF was associated with significant APD shortening and a decrease in APD adaptation to rate. While CAF significantly increased both indices of APD heterogeneity in adult dogs, it significantly decreased them in old dogs.The increase of spatial variability in repolarization in old atria may contribute to the initiation of AF in the aged. CAF-induced APD shortening and a decrease in APD adaptation appear to be important for the maintenance of sustained AF in both adult and old atria. The CAF-induced increase in dispersion of repolarization may be important for AF stabilization in adults, while previously reported fibrosis and slowed conduction of premature beats may be important in the old for both AF initiation during SR and subsequent stabilization of AF.
Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant
Authors: F P Vleggaar, H R van Buuren, P E Zondervan, F J W ten Kate, W C J Hop
Journal: Gut (2001)

The clinical and pathological findings of four females with primary biliary cirrhosis (PBC) with an unusual and hitherto not well recognised course are reported. Patients suffered severe pruritus and weight loss with progressive icteric cholestasis which did not respond to such treatments as ursodeoxycholic acid and immunosuppressives. In all cases liver histology revealed marked bile duct loss without however significant fibrosis or cirrhosis. Further diagnostic studies and repeat biopsies confirmed the absence of liver cirrhosis as well as other potential causes of hyperbilirubinaemia. Comparison of the fibrosis-ductopenia relationship for our cases with that for a group of 101 non-cirrhotic PBC patients indicated that in the former the severity of bile duct loss relative to the amount of fibrosis was significantly higher. The proportion of portal triads containing an interlobular bile duct was 3%, 4%, 6%, and 10% compared with 45% (median; range 8.3--100%) for controls (p<0.001). Three patients received a liver transplant 6--7 years after the first manifestation of PBC because of progressive cholestasis, refractory pruritus, and weight loss, while the fourth patient is considering this option. In one case cirrhosis had developed at the time of transplantation while the others still had non-cirrhotic disease. These cases suggest that cholestatic jaundice in non-cirrhotic PBC may be secondary to extensive "premature" or accelerated intrahepatic bile duct loss. Although the extent of fibrosis may be limited initially, progression to cirrhosis appears to be inevitable in the long run. Despite intact protein synthesis and absence of cirrhotic complications, liver transplantation in the pre-cirrhotic stage for preventing malnutrition and to improve quality of life should be considered for these patients.
CLINICAL EXPERIENCE WITH A NEW PHENOTHIAZINE (PIPERACETAZINE)
Authors: K. HAWORTH, L. M. JONES, W. MANDEL
Journal: American Journal of Psychiatry (1961)

Piperacetazine, a new phenothiazine derivative of the piperidine series, was clinically evaluated in 75 recently admitted hospitalized psychiatric patients. It over-all effectiveness in the treatment of the acute psychiatric disorders studies appeared comparable to that of other commonly used phenothiazine derivatives. The incidence of extrapyramidal reactions was low.
Methadone prescribing is to be reviewed in Scotland as user numbers continue to rise
Authors: B. Christie
Journal: BMJ (2012)

The use of opiate replacements such as methadone in the treatment of drug misuse is to be reviewed in Scotland after accusations that the policy had been a “disaster.”

The latest figures show that the number of drug users taking methadone has risen by 10% in the past five years to 24 507 and that methadone use is now responsible for more deaths (275 in 2011) than heroin (206).

That has led to emotive newspaper campaigns for a rethink of methadone prescribing and claims by the Scottish Conservative health spokesman, Jackson Carlaw, that its use had …
Asthma and dietary intake: an overview of systematic reviews
Authors: V. Garcia-Larsen, S. R. Del Giacco, A. Moreira, M. Bonini, D. Charles, T. Reeves, K.-H. Carlsen, T. Haahtela, S. Bonini, J. Fonseca, I. Agache, N. G. Papadopoulos, L. Delgado
Journal: Allergy (2015)

Epidemiological research on the relationship between diet and asthma has increased in the last decade. Several components found in foods have been proposed to have a series of antioxidant, anti-allergic and anti-inflammatory properties, which can have a protective effect against asthma risk. Several literature reviews and critical appraisals have been published to summarize the existing evidence in this field. In the context of this EAACI Lifestyle and asthma Task Force, we summarize the evidence from existing systematic reviews on dietary intake and asthma, using the PRISMA guidelines. We therefore report the quality of eligible systematic reviews and summarize the results of those with an AMSTAR score ≥32. The GRADE approach is used to assess the overall quality of the existing evidence. This overview is centred on systematic reviews of nutritional components provided in the diet only, as a way to establish what type of advice can be given in clinical practice and to the general population on dietary habits and asthma.
Cxcr7 Controls Neuronal Migration by Regulating Chemokine Responsiveness
Authors: Juan Antonio Sánchez-Alcañiz, Sammy Haege, Wiebke Mueller, Ramón Pla, Fabienne Mackay, Stefan Schulz, Guillermina López-Bendito, Ralf Stumm, Oscar Marín
Journal: Neuron (2011)
Prognostic predictors in younger and older incident idiopathic pulmonary arterial hypertension
Authors: Yi Ling, Martin Johnson, David Kiely, Robin Condliffe, Charlie Elliot, J. Simon R. Gibbs, Luke Howard, Joanna Pepke-Zaba, Karen Sheares, Paul Corris, Andrew Fisher, Jim Lordan, Sean Gaine, J. Gerry Coghlan, S. John Wort, Michael Gatzoulis, Andrew Peacock
Journal: European Respiratory Journal (2013)

Background:

We have recently shown that there are important phenotypic and survival differences between younger and older incident idiopathic pulmonary arterial hypertension patients (Ling et al, AJRCCM 2012;186:790-6). We sought to establish whether there are different prognostic associations between the two groups.

Methods:

Observational study of all incident idiopathic, heritable and anorexigen-associated pulmonary arterial hypertension diagnosed in all 8 pulmonary hypertension centres in the UK and Ireland between 2001-9 (n=482). Patients were divided into younger (age ≤50) and older (age>50) subgroups by the median age. Demographic and physiological data at diagnosis were analysed by multivariate Cox regression to determine independent predictors of survival.

Results:

View this table:

Predictors of survival according to age subgroups





Conclusion:

While we have shown that younger and older patients with idiopathic pulmonary arterial hypertension have different characteristics and survival, here we show that there may also be some different associations with survival between the two groups which merit further evaluation.
Effect of Propranolol on Blood Pressure and Plasma Renin Activity in the Spontaneously Hypertensive Rat
Authors: BARR H. FORMAN, PATRICK J. MULROW
Journal: Circulation Research (1974)

Spontaneously hypertensive Wistar rats have normal basal levels of plasma renin activity but do not respond to sodium depletion or the stress of ether anesthesia plus laparotomy. Both age and rat strain influence the development of this hyporesponsive renin system: normal Wistar and spontaneously hypertensive rats but not Sprague-Dawley rats develop the hyporesponsive system as they age. Therefore, these rat strains may serve as useful models for studying the effects of age and hypertension on plasma renin activity. In the present study, propranolol administration up to 18 mg/kg day -1 for 15 days did not lower plasma renin activity but did cause a paradoxical rise in blood pressure in spontaneously hypertensive rats. This paradoxical rise was prevented by placing the rats on a low-sodium diet prior to propranolol administration. The mechanism of the paradoxical rise is unknown, but we suggest that it could be the result of increased alpha-adrenergic activity in response to a fall in cardiac output.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Douglas M. Moore, S. Fai Cheuk, J. Dennis Morton, Richard D. Berlin, W. Barry Wood
Journal: The Journal of Experimental Medicine (1970)

Blood leukocytes, in contrast to exudate leukocytes, release little or no pyrogen when incubated in 0.15 M NaCl unless previously activated by exposure to endotoxin or to a protein activator that is present in acute exudate fluid. The activation process, which also occurs during phagocytosis, involves the synthesis of cellular protein, presumably related to the pyrogen molecule. Evidence is presented that generation of pyrogen in sterile inflammatory lesions depends on both the activator and the anaerobic conditions in the exudate fluid.