tbuckley/cabot-search huggingface dataset:
Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome.
Authors: S Idell, K K James, E G Levin, B S Schwartz, N Manchanda, R J Maunder, T R Martin, J McLarty, D S Fair
Journal: Journal of Clinical Investigation (1989)

To determine the possible mechanism(s) promoting alveolar fibrin deposition in the adult respiratory distress syndrome (ARDS), we investigated the initiation and regulation of both fibrinolysis and coagulation from patients with ARDS (n = 14), at risk for ARDS (n = 5), and with interstitial lung diseases (ILD) (n = 8), and normal healthy individuals (n = 13). Bronchoalveolar lavage (BAL) extrinsic pathway inhibitor activity was increased in ARDS BAL compared with patients at risk for ARDS (P = 0.0146) or normal controls (P = 0.0013) but tissue factor-factor VII procoagulant activity was significantly increased in ARDS BAL compared with all other groups (P less than 0.001). Fibrinolytic activity was not detectable in BAL of 10 of the 14 patients with ARDS and low levels of activity were found in BAL of the other four ARDS patients. Depressed fibrinolysis in ARDS BAL was not due to local insufficiency of plasminogen; rather, there was inhibition of both plasmin and plasminogen activator. Plasminogen activator inhibitor 1 was variably detected and low levels of plasminogen activator inhibitor 2 were found in two ARDS BAL samples, but plasminogen activator inhibitor 2 was otherwise undetectable. ARDS BAL antiplasmin activity was, in part, due to alpha 2-antiplasmin. We conclude that abnormalities that result in enhanced coagulation and depressed fibrinolysis, thereby predisposing to alveolar fibrin deposition, occur in the alveolar lining fluids from patients with ARDS.
Effectiveness of Removable Walker Cast Versus Nonremovable Fiberglass Off-Bearing Cast in the Healing of Diabetic Plantar Foot Ulcer
Authors: Ezio Faglia, Carlo Caravaggi, Giacomo Clerici, Adriana Sganzaroli, Vincenzo Curci, Wanda Vailati, Daniele Simonetti, Francesco Sommalvico
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate the efficacy of a removable cast walker compared with that of a nonremovable fiberglass off-bearing cast in the treatment of diabetic plantar foot ulcer. RESEARCH DESIGN AND METHODS Forty-five adult diabetic patients with nonischemic, noninfected neuropathic plantar ulcer were randomly assigned for treatment with a nonremovable fiberglass off-bearing cast (total contact cast [TCC] group) or walker cast (Stabil-D group). Treatment duration was 90 days. Percent reduction in ulcer surface area and total healing rates were evaluated after treatment. RESULTS A total of 48 patients were screened; however, 2 patients in the TCC group and 1 patient in the Stabil-D group did not complete the study and were considered dropouts. There were no significant differences in demographic and clinic characteristics of the 45 patients completing the study. Ulcer surface decreased from 1.41 to 0.21 cm2 (P &amp;lt; 0.001) in the TCC group and from 2.18 to 0.45 cm2 (P &amp;lt; 0.001) in the Stabil-D group, with no significant differences between groups (P = 0.722). Seventeen patients (73.9%) in the TCC group and 16 patients (72.7%) in the Stabil-D group achieved healing (P = 0.794). Average healing time was 35.3 ± 3.1 and 39.7 ± 4.2 days in the TCC and Stabil-D group, respectively (P = 0.708). CONCLUSIONS The Stabil-D cast walker, although removable, was equivalent in efficacy to the TCC in terms of ulcer size reduction and total healing rate. The easier use of Stabil-D may help increase the use of off-loading devices in the management of plantar neuropathic diabetic foot ulcers.
Anticoagulation With Otamixaban and Ischemic Events in Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Philippe Gabriel Steg, Shamir R. Mehta, Charles V. Pollack, Christoph Bode, Marc Cohen, William J. French, James Hoekstra, Sunil V. Rao, Witold Ruzyllo, Juan M. Ruiz-Nodar, Manel Sabaté, Petr Widimsky, Robert Gabor Kiss, Jose Luis Navarro Estrada, Hanoch Hod, Prafulla Kerkar, Sema Guneri, Murat Sezer, Mikhail Ruda, José Carlos Nicolau, Claudio Cavallini, Iftikhar Ebrahim, Ivo Petrov, Jae Hyung Kim, Myung Ho Jeong, Gabriel Arturo Ramos Lopez, Peep Laanmets, Frantisek Kovar, Christophe Gaudin, Karen C. Fanouillere, Pascal Minini, Elaine B. Hoffman, Angele Moryusef, Stephen D. Wiviott, Marc S. Sabatine
Journal: JAMA (2013)

IMPORTANCEThe optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial.OBJECTIVE To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy.DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, active-controlled superiority trial that enrolled 13 229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013.A planned interim analysis was conducted for otamixaban dose selection.INTERVENTIONS Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide.The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURESThe primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7.RESULTS Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16];P = .93).There were no differences for the secondary end points, including procedural thrombotic complications.The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78];P < .001).Results were consistent across prespecified subgroups. CONCLUSIONS AND RELEVANCEOtamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding.These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention.
Presenting the European Forum for TB Innovation: innovative thinking in progressing towards TB elimination in Europe: Table 1
Authors: Francesco Blasi, Lee B. Reichman, Giovanni Battista Migliori
Journal: European Respiratory Journal (2012)

On March 9, 2012 the European Respiratory Society (ERS) launched its first ever think tank on tuberculosis (TB): the European Forum for TB Innovation. When we, as prospective authors, sat down to tackle the content layout of this short editorial, we realised that we could not just use the academic tone that commonly characterises scientific articles. The principles that have led the ERS to embrace the discussion surrounding TB innovation transcend science and academic discussion. They are principles originating from the need to re-think TB control in Europe and beyond. We therefore felt that our personal account on how we came to agree to contribute to this new initiative was the only acceptable way of bringing this editorial to life.

I will admit it. I am not a TB expert. I started my career as a cardiologist, to later embrace the field of respiratory care with a keen interest in pneumonia. I am, in other words, not a usual suspect. But even while immersed in my clinical practice in one of the major Italian cities, Milan, I was alarmed by the subtle and ominous presence of TB.

I am not referring to the persistent and tireless reminding by ERS colleagues from the TB Assembly, that TB is everywhere and well rooted among our population. That played a role, too. But my awakening came with the realisation that TB and multidrug-resistant (MDR)-TB in Europe, in Italy and in my city were and are besieging the life of the most vulnerable and anchoring their roots among the general population again [1–8]. Silently, but relentlessly.

The realisation that, in the 21st century, the tools to control the disease and alleviate patient suffering are still those described in the textbook I used throughout medical school has led me to commit …
Bronchoalveolar lavage cell analysis in patients with human immunodeficiency virus related diseases.
Authors: V Plaza, P Jimenez, A Xaubet, C Picado, A Torres, C Agusti, A Agusti-Vidal
Journal: Thorax (1989)

The value of differential cell counts in bronchoalveolar lavage fluid in patients who were serologically positive for the human immunodeficiency virus (HIV) was studied in 30 patients with classified into four groups according to the severity of illness: (1) seven subjects with the AIDS related complex without clinical or radiological evidence of pulmonary infection; (2) eight patients with the AIDS related complex and pulmonary tuberculosis; (3) eight patients with AIDS and Pneumocystis carinii pneumonia; and (4) seven patients with AIDS, Pneumocystis carinii pneumonia, and severe respiratory failure. All four groups had a similar percentage of lymphocytes, significantly higher than that of a control group of 15 healthy volunteers. A significant increase in the percentage of neutrophils was observed in groups 2, 3, and 4. The lavage fluid differential cell count does not therefore appear to help in the differential diagnosis of pulmonary infections in HIV positive patients. The abnormal percentage of lymphocytes observed in some patients with the AIDS related complex without clinical evidence of pulmonary infection suggests that lung injury may exist before clinical or radiological abnormalities develop. This might be related to an immunological mechanism or might be caused by an undetected subclinical infection.
Cross-domain thinking: Common representation format or generalized mapping process?
Authors: Peter F. Dominey
Journal: Behavioral and Brain Sciences (2002)

In Carruthers’ formulation, cross-domain thinking requires translation of domain specific data into a common format, and linguistic LF thus plays the role of the common medium of exchange. Alternatively, I propose a process-oriented characterization, in which there is no common representation and cross-domain thinking is rather the process of establishing mappings across domains, as in the process of analogical reasoning.
Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis
Authors: Eveline Nüesch, Winfried Häuser, Kathrin Bernardy, Jürgen Barth, Peter Jüni
Journal: Annals of the Rheumatic Diseases (2012)

Objectives To synthesise the available evidence on pharmacological and non-pharmacological interventions recommended for fibromyalgia syndrome (FMS). Methods Electronic databases including MEDLINE, PsycINFO, Scopus, the Cochrane Controlled Trials Registry and the Cochrane Library were searched for randomised controlled trials comparing any therapeutic approach as recommended in FMS guidelines (except complementary and alternative medicine) with control interventions in patients with FMS. Primary outcomes were pain and quality of life. Data extraction was done using standardised forms. Results 102 trials in 14 982 patients and eight active interventions (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors (SNRIs), the gamma-amino butyric acid analogue pregabalin, aerobic exercise, balneotherapy, cognitive behavioural therapy (CBT), multicomponent therapy) were included. Most of the trials were small and hampered by methodological quality, introducing heterogeneity and inconsistency in the network. When restricted to large trials with ≥100 patients per group, heterogeneity was low and benefits for SNRIs and pregabalin compared with placebo were statistically significant, but small and not clinically relevant. For non-pharmacological interventions, only one large trial of CBT was available. In medium-sized trials with ≥50 patients per group, multicomponent therapy showed small to moderate benefits over placebo, followed by aerobic exercise and CBT. Conclusions Benefits of pharmacological treatments in FMS are of questionable clinical relevance and evidence for benefits of non-pharmacological interventions is limited. A combination of pregabalin or SNRIs as pharmacological interventions and multicomponent therapy, aerobic exercise and CBT as non-pharmacological interventions seems most promising for the management of FMS.
Cancer Risk in Nontransplanted and Transplanted Cystic Fibrosis Patients: A 10-Year Study
Authors: P. Maisonneuve, S. C. FitzSimmons, J. P. Neglia, P. W. Campbell, A. B. Lowenfels
Journal: JNCI Journal of the National Cancer Institute (2003)

Cancer in patients with cystic fibrosis (CF), the most common genetic disorder in Caucasians, has been a rare event. However, more patients now reach adulthood, and more patients undergo organ transplantation-factors associated with an increased cancer risk. Our aim was to assess the risk of cancer in nontransplanted and transplanted CF patients.We followed 28 858 patients whose data were reported to the Cystic Fibrosis Foundation patient registry from 1990 through 1999 and compared the number of cancers observed in transplanted and nontransplanted patients to the number expected from population-based cancer incidence data. All statistical tests were two-sided.In 202 999 person-years of observation of nontransplanted CF patients, 75 cancers were observed, but 69.7 were expected (standardized incidence ratio [SIR] = 1.1, 95% confidence interval [CI] = 0.8 to 1.4). Twenty-three digestive tract tumors were observed, but 4.5 were expected (SIR = 5.1, 95% CI = 3.2 to 7.6). More cancers than expected were observed of the small bowel, colon, and biliary tract but not of the stomach or rectum. We found that the deficit of non-digestive tract tumors was not statistically significant (52 observed versus 65.2 expected; SIR = 0.80, 95% CI = 0.6 to 1.0; P =.055). In 2725 person-years of observation of 1063 transplanted patients, 13 cancers were observed, but 2.05 were expected (SIR = 6.3, 95% CI = 3.4 to 10.8), and more digestive tract tumors (four observed versus 0.19 expected; SIR = 21.2, 95% CI = 5.8 to 54.2) and lymphomas (seven observed versus 0.16 expected; SIR = 44.0, 95% CI = 17.7 to 90.7) were observed than expected.We observed an increased risk of digestive tract cancers among adult CF patients, particularly of the small bowel, colon, and biliary tract. This increased risk appeared to be more pronounced in patients who had had an organ transplantation.
Flaxseed and Its Lignans Inhibit Estradiol-Induced Growth, Angiogenesis, and Secretion of Vascular Endothelial Growth Factor in Human Breast Cancer Xenografts <i>In vivo</i>
Authors: Malin Bergman Jungeström, Lilian U. Thompson, Charlotta Dabrosin
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, which is crucial in cancer progression. We have previously shown that estradiol (E2) increases VEGF in breast cancer. Phytoestrogens are potential compounds in breast cancer prevention and treatment by poorly understood mechanisms. The main phytoestrogens in Western diet are lignans, and flaxseed is a rich source of the mammalian lignans enterodiol and enterolactone. Experimental Design: In the present study, ovariectomized mice were treated with continuous release of E2. MCF-7 tumors were established and mice were fed with basal diet or 10% flaxseed, and two groups that were fed basal diet received daily injections with enterodiol or enterolactone (15 mg/kg body weight). Results: We show that flaxseed, enterodiol, and enterolactone counteracted E2-induced growth and angiogenesis in solid tumors. Extracellular VEGF in vivo, sampled using microdialysis, in all intervention groups was significantly decreased compared with tumors in the basal diet group. Our in vivo findings were confirmed in vitro. By adding enterodiol or enterolactone, E2-induced VEGF secretion in MCF-7 cells decreased significantly without agonistic effects. The increased VEGF secretion by E2 in MCF-7 cells increased the expression of VEGF receptor-2 in umbilical vein endothelial cells, suggesting a proangiogenic effect by E2 by two different mechanisms, both of which were inhibited by the addition of lignans. Conclusions: Our results suggest that flaxseed and its lignans have potent antiestrogenic effects on estrogen receptor–positive breast cancer and may prove to be beneficial in breast cancer prevention strategies in the future.
Rapid Identification of Myocardial Infarction Risk Associated With Diabetes Medications Using Electronic Medical Records
Authors: John S. Brownstein, Shawn N. Murphy, Allison B. Goldfine, Richard W. Grant, Margarita Sordo, Vivian Gainer, Judith A. Colecchi, Anil Dubey, David M. Nathan, John P. Glaser, Isaac S. Kohane
Journal: Diabetes Care (2009)

OBJECTIVE To assess the ability to identify potential association(s) of diabetes medications with myocardial infarction using usual care clinical data obtained from the electronic medical record. RESEARCH DESIGN AND METHODS We defined a retrospective cohort of patients (n = 34,253) treated with a sulfonylurea, metformin, rosiglitazone, or pioglitazone in a single academic health care network. All patients were aged >18 years with at least one prescription for one of the medications between 1 January 2000 and 31 December 2006. The study outcome was acute myocardial infarction requiring hospitalization. We used a cumulative temporal approach to ascertain the calendar date for earliest identifiable risk associated with rosiglitazone compared with that for other therapies. RESULTS Sulfonylurea, metformin, rosiglitazone, or pioglitazone therapy was prescribed for 11,200, 12,490, 1,879, and 806 patients, respectively. A total of 1,343 myocardial infarctions were identified. After adjustment for potential myocardial infarction risk factors, the relative risk for myocardial infarction with rosiglitazone was 1.3 (95% CI 1.1-1.6) compared with sulfonylurea, 2.2 (1.6-3.1) compared with metformin, and 2.2 (1.5-3.4) compared with pioglitazone. Prospective surveillance using these data would have identified increased risk for myocardial infarction with rosiglitazone compared with metformin within 18 months of its introduction with a risk ratio of 2.1 (95% CI 1.2-3.8). CONCLUSIONS Our results are consistent with a relative adverse cardiovascular risk profile for rosiglitazone. Our use of usual care electronic data sources from a large hospital network represents an innovative approach to rapid safety signal detection that may enable more effective postmarketing drug surveillance.
Exercise in primary prevention of osteoporosis in women.
Authors: E.J Bassey
Journal: Annals of the Rheumatic Diseases (1995)

After treatment with human normal IgM, 78 +/- 8% of purified CD3-CD56+ resting human NK cells and 93 +/- 6% of IL-2-activated NK cells selected by adherence to plastic reacted with FITC-goat anti-human IgM. Binding of IgM to the FcR for IgM (Fc mu R) on human NK cells was not species specific because mouse myeloma IgM also bound to these cells. The percentage of CD56+ cells binding IgM after incubation with anti-CD16 mAb was similar to that of cells incubated with medium alone (95 +/- 1% vs 93 +/- 4%). Binding of anti-CD16 mAb to Fc gamma RIII on NK cells was unaffected by pretreatment with IgM (65 +/- 12% vs 69 +/- 4%). The CD7 molecule has been reported to be the Fc mu R on the surface of T cells. Two-color flow cytometry showed that 94 +/- 3% of CD3-CD56+ resting NK cells and 71 +/- 16% of activated NK cells were CD7+. Preincubation of NK cells with three anti-CD7 mAb (Leu-9, 8H8-1, and LAU-A1) failed to block the binding of IgM to the Fc mu R. Modulation of the CD7 molecule off the cell surface (CD7+ = 1.5% +/- 0.3) did not reduce IgM binding, thus excluding the possibility that IgM anti-CD7 might bind to different epitopes of the same molecule. These data indicate that the Fc mu R is a specific Ig-binding structure, distinct from the Fc gamma RIII (CD16) or CD7. The Fc mu R on NK cells functions as a signal-transducing molecule because the addition of 0.2 mg/ml IgM to R-NK cells caused a rapid increase in [Ca2+]i (delta = 40 nM). One of the early events that followed signaling through the Fc mu R was the down-modulation of IFN-gamma gene expression and IFN gamma production in NK cells. The presence of IgM during culture of NK cells consistently decreased the expression of HLA-DR (16% vs 40% in control). Thus, the Fc mu R, a constitutively-expressed receptor on human NK cells, seems to be an important functional molecule, which delivers negative regulatory signals to NK cells.
The timed up and go test and quadriceps strength in COPD
Authors: Ali Albarrati, Nichola Gale, Stephanie Enright, Iain Munnery, Margaret Munnery, John Cockcroft, Dennis Shale
Journal: European Respiratory Journal (2013)

Background   The Timed Up and Go (TUG) test is a simple and rapid measure of submaximal physical activity in elderly. In COPD, the TUG is prolonged and it relates to the six-minute walk distance (6MWD), which reflects similar impairment in the elderly. We hypothesised that the TUG would relate to quadriceps muscle strength.   Methods   In 190 patients COPD, isometric quadriceps maximum voluntary contraction (QMVC), 6MWD, the COPD assessment test (CAT), spirometry and the TUG were determined.   Results   Patients (97 males) mean age 67±7 years and FEV 1 % predicted 57±15. The QMVC, TUG and 6MWD were related to FEV 1 % predicted, p   Conclusion   The TUG test, an integrated measure of strength, balance and function, was closely associated to the 6MWD, was related similarly to the CAT score and predicted quadriceps muscle strength. These parallels between the 6MWD and TUG with its rapid and simple performance suggests the TUG test could be used in both research and clinical settings to assess the impact of COPD on exercise performance.