tbuckley/cabot-search huggingface dataset:
Increased Airway Smooth Muscle Mass in Children with Asthma, Cystic Fibrosis, and Non-Cystic Fibrosis Bronchiectasis
Authors: Nicolas Regamey, Matthias Ochs, Tom N. Hilliard, Christian Mühlfeld, Nikki Cornish, Louise Fleming, Sejal Saglani, Eric W. F. W. Alton, Andrew Bush, Peter K. Jeffery, Jane C. Davies
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Structural alterations to airway smooth muscle (ASM) are a feature of asthma and cystic fibrosis (CF) in adults.Objectives: We investigated whether increase in ASM mass is already present in children with chronic inflammatory lung disease.Methods: Fiberoptic bronchoscopy was performed in 78 children (median age [IQR], 11.3 [8.5–13.8] yr): 24 with asthma, 27 with CF, 16 with non-CF bronchiectasis (BX), and 11 control children without lower respiratory tract disease. Endobronchial biopsy ASM content and myocyte number and size were quantified using stereology.Measurements and Main Results: The median (IQR) volume fraction of subepithelial tissue occupied by ASM was increased in the children with asthma (0.27 [0.12–0.49]; P < 0.0001), CF (0.12 [0.06–0.21]; P < 0.01), and BX (0.16 [0.04–0.21]; P < 0.01) compared with control subjects (0.04 [0.02–0.05]). ASM content was related to bronchodilator responsiveness in the asthmatic group (r = 0.66, P < 0.01). Median (IQR) myocyte number (cells per mm2 of reticular basement membrane) was 8,204 (5,270–11,749; P < 0.05) in children with asthma, 4,504 (2,838–8,962; not significant) in children with CF, 4,971 (3,476–10,057; not significant) in children with BX, and 1,944 (1,596–6,318) in control subjects. Mean (SD) myocyte size (μm3) was 3,344 (801; P < 0.01) in children with asthma, 3,264 (809; P < 0.01) in children with CF, 3,177 (873; P < 0.05) in children with BX, and 1,927 (386) in control subjects. In all disease groups, the volume fraction of ASM in subepithelial tissue was related to myocyte number (asthma: r = 0.84, P < 0.001; CF: r = 0.81, P < 0.01; BX: r = 0.95, P < 0.001), but not to myocyte size.Conclusions: Increases in ASM (both number and size) occur in children with chronic inflammatory lung diseases that include CF, asthma, and BX.
Calcium and vitamin D in preventing fractures: Data are not sufficient to show inefficacy
Authors: Alex Vasquez, John Cannell
Journal: BMJ (2005)

Calcium and vitamin D in preventing fractures Vitamin K supplementation has powerful effectEditor-Porthouse et al conducted a good randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D 3 ) for prevention of fractures in primary care. 1 However, vitamin D and calcium are not enough.No mention was made of the extensive research from Japan and the Netherlands, which shows that vitamin K supplementation has a powerful effect in decreasing osteoporosis and osteoporosis related fractures.Combining vitamin K, vitamin D, and calcium seems ideal.Researchers from Osaka Medical College showed that vitamin K and vitamin D together increased bone density much better than vitamin K alone. 2hen comparing calcium and vitamin D alone with placebo, researchers at the University of Maastricht found little benefit on bone loss.But those randomised to take vitamin K in addition to calcium and vitamin D had significantly less femoral neck bone loss after three years. 3he Yamaguchi osteoporosis prevention study showed that vitamin K alone reduced vertebral fractures by 56% compared to placebo, comparable to the benefit found from etidronate. 4 Researchers at Hirosaki University in Japan showed that vitamin K lowered bone fractures in elderly female patients with Parkinson's by 90%. 5 The same research team showed an 86% decrease in fractures in elderly patients with Alzheimer's treated with a combination of vitamin K, vitamin D, and calcium compared with placebo.w1 If the medical standard became to first use vitamins D and K with calcium before using bisphosphonates or selective oestrogen receptor modulators, the public would save billions of dollars a year.
THE EFFECT OF DINITROPHENOL AND THYROXIN ON THE SUSCEPTIBILITY OF MICE TO STAPHYLOCOCCAL INFECTIONS
Authors: J. Maclean Smiths, René J. Dubos
Journal: The Journal of Experimental Medicine (1956)

Mice were given daily per os amounts of dinitrophenol or of thyroid extract sufficient to prevent or retard the normal weight gain of uninfected animals, but not large enough to cause their death. When mice maintained on these regimens for 1 or 2 weeks were infected with staphylococci, most of them died within 12 days-much more rapidly than did mice fed a normal diet. Deaths occurred even when the organism injected was a non-virulent staphylococcus, unable to cause fatal disease in mice fed a normal diet. There was some suggestion that thyroid treatment interfered with the bactericidal mechanism in the liver, spleen, and kidneys of mice during the initial phase of infection. In contrast there was no clear evidence at any time thereafter that either thyroid extract or dinitrophenol caused the staphylococci to multiply more rapidly in the various organs.
Contact allergy induced by bisphenol A diglycidyl ether leachables from aluminium tubes for pharmaceutical use
Authors: K. Breuer, C. Lipperheide, U. Lipke, T. Zapf, H. Dickel, R. Treudler, S. Molin, V. Mahler, C. Pföhler, H. Löffler, H. Schwantes, A. Schnuch
Journal: Allergy (2014)

Background Aluminium tubes for pharmaceutical use are internally lacquered with epoxy resins (ER) based on bisphenol A diglycidyl ether (BADGE). Recently, it was shown that remnants of ER polymerization like BADGE are extractable from epoxy-based coatings of commercially available tubes and may leach into semi-solid drug preparations. We aimed to evaluate the safety of BADGE-contaminated macrogol ointments in individuals sensitized to ER based on BADGE by use tests. Methods Repeated open application testing (ROAT) in 11 patients sensitized to ER based on BADGE with BADGE in macrogol ointments (3 mg/kg; 30 mg/kg, equivalent to BADGE concentration determined in macrogol ointment after storage in a commercially available tube; 300 mg/kg). Results The 30 mg/kg BADGE ointment elicited reactions in three patients, and another three patients reacted to 300 mg/kg BADGE ointment. No reactions to the vehicle control and 3 mg/kg BADGE were observed. Conclusions Elevated BADGE concentrations in ER-coated aluminium tubes pose a risk of developing contact dermatitis to patients sensitized to ER based on BADGE. Quality standards are deemed necessary for the production of ER-coated aluminium tubes intended for pharmaceutical use and should consider the results of the present ROAT study.
Ultrasound-guided intra-articular injections in the wrist in patients with rheumatoid arthritis: a double-blind, randomised controlled study
Authors: K R Luz, R N V Furtado, C C G Nunes, A Rosenfeld, A R C Fernandes, J Natour
Journal: Annals of the Rheumatic Diseases (2008)

genotype was more common among patients with RA (p,0.001).Furthermore, this difference reached significance after performing the Armitage trend test (p = 0.005).These association are in agreement with the results found in other autoimmune diseases. [3]4][5] However, these results should be considered with caution since a departure of HWE for this genetic variant was found in the control group.Noticeably, an independent control population from northern Spain showed very similar genotypic frequencies to our population and departure from HWE as well. 6 No significant differences were seen between patients with RA and controls for the CD24 TG/del polymorphism (table 1).The possibility that this lack of association might have arisen owing to type II error seems unlikely, since we estimated that our cohort has enough power (.90%) to detect the effect of the polymorphism considering an OR of 1.5 at 5% significance level.However, this finding contradicts a recent report which shows that TG deletion from the CD24 mRNA translation start site is associated with a reduced risk and progression of multiple sclerosis and systemic lupus erythematosus. 4 In addition, the haplotype defined by the two markers tested was also analysed.Although a significant association with protection from RA was found with the CD24 A/TG haplotype (p = 0.03) that turned out to be non-significant after the Bonferroni correction test was applied (p corr = 0.09).These findings are further evidence that specific disease-relevant alleles for some susceptibility genes vary between different populations or diseases.To conclude, it appears that the CD24 A57V polymorphism plays a role in the susceptibility to RA in a Spanish population.
Pyrvinium Attenuates Hedgehog Signaling Downstream of Smoothened
Authors: Bin Li, Dennis Liang Fei, Colin A. Flaveny, Nadia Dahmane, Valérie Baubet, Zhiqiang Wang, Feng Bai, Xin-Hai Pei, Jezabel Rodriguez-Blanco, Brian Hang, Darren Orton, Lu Han, Baolin Wang, Anthony J. Capobianco, Ethan Lee, David J. Robbins
Journal: Cancer Research (2014)

The Hedgehog (HH) signaling pathway represents an important class of emerging developmental signaling pathways that play critical roles in the genesis of a large number of human cancers. The pharmaceutical industry is currently focused on developing small molecules targeting Smoothened (Smo), a key signaling effector of the HH pathway that regulates the levels and activity of the Gli family of transcription factors. Although one of these compounds, vismodegib, is now FDA-approved for patients with advanced basal cell carcinoma, acquired mutations in Smo can result in rapid relapse. Furthermore, many cancers also exhibit a Smo-independent activation of Gli proteins, an observation that may underlie the limited efficacy of Smo inhibitors in clinical trials against other types of cancer. Thus, there remains a critical need for HH inhibitors with different mechanisms of action, particularly those that act downstream of Smo. Recently, we identified the FDA-approved anti-pinworm compound pyrvinium as a novel, potent (IC50, 10 nmol/L) casein kinase-1α (CK1α) agonist. We show here that pyrvinium is a potent inhibitor of HH signaling, which acts by reducing the stability of the Gli family of transcription factors. Consistent with CK1α agonists acting on these most distal components of the HH signaling pathway, pyrvinium is able to inhibit the activity of a clinically relevant, vismodegib -resistant Smo mutant, as well as the Gli activity resulting from loss of the negative regulator suppressor of fused. We go on to demonstrate the utility of this small molecule in vivo, against the HH-dependent cancer medulloblastoma, attenuating its growth and reducing the expression of HH biomarkers.
Predicting Corticosteroid Response in Chronic Obstructive Pulmonary Disease Using Exhaled Nitric Oxide
Authors: Jack F. Dummer, Michael J. Epton, Jan O. Cowan, Julie M. Cook, Robin Condliffe, C. Erik Landhuis, Andrew D. Smith, D. Robin Taylor
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Predicting corticosteroid response in COPD is important but difficult. Response is more likely to occur in association with eosinophilic airway inflammation, for which the fraction of exhaled nitric oxide (Fe(NO)) is a good surrogate marker.We aimed to establish whether Fe(NO) levels would predict the clinical response to oral corticosteroid in COPD.We performed a double-blind, crossover trial of steroid in patients with COPD. After a 4-week washout of inhaled steroids, patients received prednisone 30 mg/d or matching placebo, in random order, with an intervening 4-week washout. The predictive values of Fe(NO) for clinically significant changes in 6-minute-walk distance (6MWD), spirometry (FEV(1)), and St. George's Respiratory Questionnaire (SGRQ) were calculated.A total of 65 patients (mean FEV(1) = 57% predicted) were randomized. With prednisone, there was a net increase of 13 m in 6MWD (P = 0.02) and 0.06 L in postbronchodilator FEV(1) (P = 0.02) compared with placebo. The change in SGRQ was not significant. Using receiver operator characteristic analysis, the area under the curve for an increase of 0.2 L in FEV(1) was 0.69 (P = 0.04) with an optimum Fe(NO) cut-point of 50 ppb. The positive and negative predictive values were 67 and 82%, respectively. FE(NO) was not a significant predictor for changes in 6MWD or SGRQ.Fe(NO) is a weak predictor of short-term response to oral corticosteroid in COPD, its usefulness being limited to predicting increase in FEV(1). Clinical trial registered with www.anzctr.org.au (ACTRN12605000683639).
Beliefs and attitudes of health care workers on influenza and pneumococcal vaccine
Authors: Fatma Ciftci, Elif Sen, Nalan Demir, Oya Kayacan
Journal: European Respiratory Journal (2012)

It is recommended to vaccinate health care workers against influenza and streptococcus pneumoniae if at risk group. This study is done to determine the vaccination rates and attitudes on vaccines of health care workers. A total of 192 health care workers (100 female, 92 males) consisting of 55 nurses, 42 health officers, 21 paramedics, 19 medical secretaries, 52 auxiliary staff, and 3 domestic health care givers were questioned between October 2011-January 2012. One-hundred and fifty-five (80.7%) health care workers were nonvaccinated against influenza. The reasons of this were fear of side effects (% 30,2 (n:29), doubt on efficacy (%27,1 (26), unawaraness of the vaccine (%23,5 (n:23), doubt on safety (%19,8 (n:19), and lack of adequate data %16,8 (n:16). Sixty-eight (48.6%) of influenza-nonvaccinated workers recommended patients vaccination whereas 23 (69.7%) of vaccinated workers recommended the vaccine. Vaccine recommendation rates of influenza-vaccinated workers were significantly higher. Pneumococcal vaccinatation recommendation rates were similar in influenza-vaccinated or nonvaccinated workers. Six (3.4%) health care workers were vaccinated against streptoccocus pneumoniae. Vaccine recommendation rates for pneumococcal vaccine were significantly higher in vaccinated than nonvaccinated workers (66% and 48%, respectively). The reasons for nonvaccination were fear of side effects (% 28,9 (n:33), doubt on efficacy (%25,4 (n:29), unawareness of the vaccine (%23,1 (n:27), doubt on safety (%20,2 (n:23), and lack of adequate data (%16,8 (n:19).  As a conclusion, health care workers have a low rate of vaccination and recommendation of vaccination against influenza and streptococcus pneumoniae.
Effects of Hypothyroidism on Estrogen-Induced Inhibition of Coronary Atherogenesis in Cholesterol-Fed Cockerels
Authors: RUTH PICK, JEREMIAH STAMLER, LOUIS N. KATZ, Philip Johnson, Dolores Friedman
Journal: Circulation Research (1957)

This report deals with the question of whether hypothyroidism induced in various ways can influence the ability of estrogens to prevent coronary atherosclerosis in cholesterol-fed chicks.
Combining isometric knee extension exercises with hip adduction or abduction does not increase quadriceps EMG activity
Authors: J Hertel, J E Earl, K K W Tsang, S J Miller
Journal: British Journal of Sports Medicine (2004)

Objective: To determine if the combined isometric contractions of knee extension/hip adduction and knee extension/hip abduction will elicit a different quadriceps and gluteus medius electromyographic (EMG) pattern as compared to isometric contraction of a uniplanar knee extension exercise. Methods: Eight healthy young adult volunteers without history of knee or quadriceps injury participated. Surface EMG data were collected from the vastus medialis oblique (VMO), vastus lateralis (VL), and gluteus medius (Gmed) muscles of the dominant leg of each subject during three single leg, weight bearing, isometric exercises (uniplanar knee extension, knee extension/hip adduction, knee extension/hip abduction). All exercises were performed at a position of 60° knee flexion. Three trials lasting 5 s each were performed for each of the three exercises. EMG data from each muscle were integrated and the maximum root mean square activity over a 0.5 s window for each trial was averaged. Analyses of variance were performed with exercise (straight extension, extension/adduction, extension/abduction) as the independent variable and VMO, VL, and Gmed activity and VMO:VL ratio as dependent variables. Results: A significant main effect for exercise was found for the VMO (p = 0.006) and VL (p = 0.02), but not the Gmed (p = 0.25) or the VMO:VL ratio (p = 0.13). For the VMO and VL, the uniplanar knee extension task produced significantly more EMG activity than the extension/adduction or extension/abduction tasks. Conclusions: Uniplanar knee extension exercises may be more appropriate than combining isometric knee extension exercises with hip adduction or abduction when eliciting maximal VMO and VL contractions.
Evaluation of assays for antibody to hepatitis E virus by a serum panel
Authors: Eric E. Mast, Miriam J. Alter, Paul V. Holland, Robert H. Purcell
Journal: Hepatology (1998)

Few data are available to evaluate the performance of existing assays for antibody to the hepatitis E virus (anti-HEV). A panel of 164 randomized and coded sera was tested for anti-HEV by 12 different assays. The panel included a dilution series of an early convalescent human serum, known-positive sera (undiluted human sera obtained 2 months to 13 years after acute hepatitis E, and postinoculation chimpanzee sera), known-negative sera (preinoculation chimpanzee sera; sera from chimpanzees with hepatitis A virus, hepatitis B virus, or hepatitis C virus infection; and normal human sera), and sera obtained from previously tested U.S. blood donors without a history of hepatitis. Six tests detected anti-HEV in > or =90% of undiluted known-positive sera. The sensitivity of all of the assays with known-positive sera ranged from 17% to 100%, and the limit of detection by endpoint dilution ranged from 1:5 to 1:160. Ten tests were nonreactive for all of the 22 known-negative sera, one test was reactive for one serum, and one test was reactive for 5 sera. In pairwise comparisons of different tests in blood donor sera, the overall concordance ranged from 49% to 94% (median, 69%) and the concordance among reactive sera ranged from 0% to 89% (median, 32%). Several of these tests performed well in detecting anti-HEV in known positive sera. However, highly discrepant results among U.S. blood donor sera indicate that anti-HEV seroprevalence data in non-HEV-endemic countries may be unreliable and should be interpreted with caution.
Acetylcholine induces contractile and relaxant effects in canine nasal venous systems
Authors: M. Wang, M. A. Lung
Journal: European Respiratory Journal (2006)

Acetylcholine (ACh) induces nasal congestion at low doses but decongestion at high doses. The current study investigated the vascular mechanisms underlying this biphasic nasal airway response in dogs. Collecting and outflow veins from anterior and posterior nasal venous systems and the septal mucosa (containing sinusoidal venous plexuses) were isolated. The in vitro isometric tension of the vascular segments was monitored to reflect vascular reactivity. Immunohistochemical localisation of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and endothelial nitric oxide synthase (eNOS) was performed. ACh did not affect the venous plexuses but contracted the anterior collecting vein and the outflow veins of both systems in a concentration-dependent manner; the responses were unaffected by nitro- L -arginine-methyl-ester ( L -NAME). ACh relaxed posterior collecting veins at low concentrations but contracted them at higher concentrations; L -NAME enhanced the contractions but inhibited the relaxations, with the inhibition reversed by L -arginine. NADPH-diaphorase and eNOS were located predominantly in the posterior collecting veins. The fact that acetylcholine at low concentrations relaxes posterior collecting veins but contracts other collecting and outflow veins implies that the agonist in vivo may induce nasal congestion by increasing posterior blood volume. At higher concentrations, acetylcholine contracts posterior collecting veins as well, implying diminished blood volume in both venous systems, and consequently nasal decongestion. The induced contraction in posterior collecting veins is nitric oxide-independent, while the induced relaxation is nitric oxide-dependent.
Comparative Analysis of Regulatory and Effector T Cells in Progressively Growing versus Rejecting Tumors of Similar Origins
Authors: Jack D. Bui, Ravindra Uppaluri, Chyi-Song Hsieh, Robert D. Schreiber
Journal: Cancer Research (2006)

Although regulatory T cells (Tregs) have been detected in clinically apparent and experimentally induced tumors, the significance of their presence is obscured because past studies examined late-stage tumors that had formed in immunocompetent hosts and thus had evolved mechanisms to escape immunologic recognition and/or elimination. Herein, we report the first comparative analysis of the antitumor response to 3'-methylcholanthrene-induced tumors, which either grow progressively (progressor tumors) or are rejected by the immune system (regressor tumors). Surprisingly, we found that both progressor and regressor tumors harbored proliferating (i.e., activated) Foxp3+CD25+Tregs. However, progressor tumors contained a higher percentage of Tregs in the lymphocyte subset versus regressor tumors. The Tregs in progressor tumors were derived from peripheral CD25+ natural Tregs, accumulated early after tumor challenge and were actively proliferating, suggesting that progressor tumors recruited and/or activated endogenous Tregs as a mechanism of escaping immune destruction. To explore whether Tregs directly contributed to the progressive growth phenotype of progressor tumors, we monitored tumor outgrowth in naive wild-type recipients pretreated with either a control monoclonal antibody (mAb) or a depleting CD25-specific mAb. In mice predepleted of CD25+ cells, the tumors that subsequently developed displayed an increased accumulation of proliferating CD8+ T cells and were rejected. These results show that, although Tregs are activated in both regressor and progressor tumors, the ratio of regulatory to effector T cells is critical in determining whether the host successfully rejects the tumor or eventually succumbs to tumor outgrowth.
Weekly Paclitaxel and Gemcitabine in Advanced Transitional-Cell Carcinoma of the Urothelium: A Phase II Hoosier Oncology Group Study
Authors: Jinxing Li, Beth Juliar, Constantin Yiannoutsos, Rafat Ansari, Edward Fox, Michael J. Fisch, Lawrence H. Einhorn, Christopher J. Sweeney
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the efficacy and toxicity of weekly paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma (TCC) of the urothelial tract. Patients and Methods Patients with advanced unresectable TCC were enrolled onto this multicenter, community-based, phase II trial. Initially, patients were treated with paclitaxel 110 mg/m 2 and gemcitabine 1,000 mg/m 2 by intravenous infusion on days 1, 8, and 15 every 28 days. Patients who had an objective response or stable disease continued treatment for a maximum of six courses. Paclitaxel was decreased to 90 mg/m 2 and gemcitabine was decreased to 800 mg/m 2 for the last 12 patients because of a concerning incidence of pulmonary toxicity in the first 24 patients. Results Thirty-six patients were enrolled between September 1998 and March 2003. Twenty-four patients received the higher doses of paclitaxel and gemcitabine, and 12 patients received the lower doses. Twenty-five (69.4%) of 36 patients had major responses to treatment, including 15 patients (41.7%) with complete responses. With a median follow-up time of 38.7 months, the median survival time was 15.8 months. Grade 3 and 4 toxicities included granulocytopenia (36.1%), thrombocytopenia (8.3%), and neuropathy (16.7%). Five patients (13.9%) had grades 3 to 5 pulmonary toxicity, and one patient had grade 2 pulmonary toxicity. Conclusion Weekly paclitaxel and gemcitabine is an active regimen in the treatment of patients with advanced TCC. However, because of the high incidence of pulmonary toxicity associated with this schedule of paclitaxel and gemcitabine, we recommend against the use of this regimen in this patient population.