tbuckley/cabot-search huggingface dataset:
Fatal postoperative airway obstruction in a patient with rheumatoid arthritis
Authors: T. Lehmann, W. Nef, B. Stalder, D. Thomson, N. J Gerber
Journal: Annals of the Rheumatic Diseases (1997)

<h3>Objective:</h3> To undertake a systematic review and meta-analysis of studies that investigated prognostic factors and survival in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). <h3>Background:</h3> PSP and MSA are relentlessly progressive neurodegenerative conditions that are associated with a poor prognosis. Numerous primary studies have examined prognostic factors in PSP and MSA but a systematic review or meta-analysis has not been undertaken previously. <h3>Design/Methods:</h3> Publications of at least 10 patients with a likely or confirmed diagnosis of PSP or MSA were eligible for inclusion. Methodological quality was rated using a modified version of the Quality in Prognostic Studies tool. For frequently examined prognostic factors, hazard ratios (HR) derived by univariate and multivariate analysis were pooled in separate subgroups; other results were synthesised narratively and HRs could not be reported here. <h3>Results:</h3> Thirty-seven studies presenting findings on 6257 patients (1911 PSP, 4346 MSA) fulfilled the inclusion criteria. We identified the following variables as unfavourable predictors of survival: In PSP: PSP-Richardson’s phenotype (univariate HR: 2.53; 95%CIs: 1.69, 3.78), early dysphagia and early cognitive symptoms. In MSA: severe dysautonomia and early development of combined autonomic and motor features. In PSP and MSA: early falls (multivariate HR: 2.32; 95%CIs: 1.94, 2.77), the NNIPPS Parkinson plus score and the Clinical Global Impression disease severity score. Sex (multivariate HR: 0.93; 95%CIs: 0.67, 1.28) and MSA phenotype (multivariate HR: 1.22; 95%CIs: 0.83, 1.80) did not predict survival and there was conflicting evidence regarding the prognostic effect of age at disease onset. <h3>Conclusions:</h3> Several clinical variables were strongly associated with shorter survival in PSP and MSA. Results on most prognostic factors were consistent across methodologically diverse studies; however, the lack of commonality of prognostic factors investigated is a significant limitation. <b>Disclosure:</b> Dr. Glasmacher has nothing to disclose. Dr. Leigh has received personal compensation for activities with GSK and Biogen Idec as an advisory board member. Dr. Saha has nothing to disclose.
A role for nitric oxide in hydroxyurea-mediated fetal hemoglobin induction
Authors: S. Bruce King
Journal: Journal of Clinical Investigation (2003)

Hydroxyurea is a newly approved therapeutic agent for the treatment of sickle-cell disease. Hydroxyurea reduces the number of painful crises in sickle-cell patients presumably by increasing the levels of fetal hemoglobin, which has a large solubilizing effect on sickle-cell hemoglobin and reduces polymerization (1). Despite being used to treat a number of cancers for nearly 30 years, the mechanism of how hydroxyurea increases fetal hemoglobin levels remains unclear. In this issue of the JCI, Cokic et al. present results that provide the first explanation of how hydroxyurea increases fetal hemoglobin levels (2). Specifically, they show that fetal hemoglobin increases in response to activation of soluble guanylyl cyclase (sGC) by hydroxyurea-derived NO. The importance of this work manifests itself in at least three ways: 1) the in vitro identification of some of the molecular species involved in fetal hemoglobin induction, 2) a further demonstration of a role for NO in the activity of hydroxyurea, and 3) the application of this work to the development of new NO based treatments for sickle-cell disease.

The work described in this study (2) relies on the authors’ ability to recognize clues from previous basic and clinical research. First, hydroxyurea reacts with enzymes and proteins, particularly heme-containing proteins, to release NO (3–7). Other studies reveal that patients taking hydroxyurea demonstrate increased levels of nitrite, nitrate, and iron nitrosyl hemoglobin, all of which are markers for NO (8–10). Finally, sGC activators increase γ-globin gene expression in both eryth-roleukemic cells and primary human erythroblasts and sGC inhibitors prevent this increase (11). The combination of these results with the ability of NO to stimulate sGC led to the design and execution of the described experiment to determine the effect of nitric oxide donors and hydroxyurea on fetal hemoglobin induction.
Pneumothorax in HIV-infected patients: role of Pneumocystis carinii pneumonia and pulmonary tuberculosis
Authors: M Tumbarello, E Tacconelli, T Pirronti, R Cauda, L Ortona
Journal: European Respiratory Journal (1997)

Patients with acquired immune deficiency syndrome (AIDS) are at increased risk for pneumothorax, which usually occurs in the setting of Pneumocystis carinii pneumonia. The rationale of the present study was based on the hypothesis that the increased incidence of pulmonary tuberculosis in human immunodeficiency virus (HIV)-infected patients could favour the development of pneumothorax in such patients. A case-control study was performed comprising 140 HIV-infected patients grouped as follows: 35 patients with pneumothorax and 105 matched controls without pneumothorax. Univariate analysis identified four risk factors for pneumothorax: 1) previous P. carinii pneumonia (p=0.01); 2) current P. carinii pneumonia (p=0.02); 3) pulmonary tuberculosis (p=0.01); and 4) cysts, pneumatoceles or bullae on chest radiographs (p&lt;0.001). Multivariate analysis indicated that current P. carinii pneumonia (p=0.01) and pulmonary tuberculosis (p=0.04) were both independent risk factors for pneumothorax. In conclusion, our findings demonstrate that, in addition to Pneumocystis carinii pneumonia, pulmonary tuberculosis enhances the risk of pneumothorax in patients with acquired immune deficiency syndrome.
PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis
Authors: Jancy Stephen, Chris Delvecchio, Naomi Spitale, Amanda Giesler, Katherine Radford, Pat Bilan, P. Gerard Cox, John P. Capone, Parameswaran Nair
Journal: European Respiratory Journal (2012)

Airway smooth muscle cells produce extracellular matrix proteins, which in turn can promote smooth muscle survival, proliferation and migration. Currently available therapies have little effect on airway smooth muscle matrix production and migration. Peroxisome proliferator-activated receptor (PPAR) ligands are reported to decrease migration and matrix production in various cell lines. In this study, we examined the effect of PPAR ligands on human airway smooth muscle (HASM) matrix production and migration. PPAR expression was examined by RT-PCR and Western blotting. Endogenous PPAR activity was examined by transfecting cells with a PPAR response element-luciferase reporter plasmid. We observed that HASM cells express PPARα, β and γ. A six-fold induction of luciferase activity was observed by stimulating cells with a pan-agonist, indicating endogenous PPAR activity. The PPAR ligands ciglitazone, 15-deoxy-Δ12,14-prostaglandin J(2) and WY-14643 decreased migration towards platelet-derived growth factor receptor. This was not mediated by inhibiting Akt phosphorylation or promoting PTEN activity, but partly through cyclooxygenase-2 induction and prostaglandin E(2) production that increased cyclic AMP levels in the cells. All three ligands also caused an inhibition of collagen and fibronectin secretion by cultured smooth muscle cells. We conclude that PPAR ligands decrease HASM migration and matrix production and are, therefore, potentially useful for modulating airway remodelling.
THE CHLORACETIC ACIDS: A BIOCHEMICAL STUDY
Authors: H. LESLIE ROBERTS
Journal: British Journal of Dermatology (1926)

Journal Article THE CHLORACETIC ACIDS: A BIOCHEMICAL STUDY Get access H. LESLIE ROBERTS, M.D. H. LESLIE ROBERTS, M.D. Lately Lecturer in Dermatology in the University of Liverpool; Consulting Dermatologist to the Liverpool Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 38, Issue 10, 1 October 1926, Pages 375–391, https://doi.org/10.1111/j.1365-2133.1926.tb09235.x Published: 01 October 1926
Fecal Occult Blood Testing When Colonoscopy Capacity is Limited
Authors: Janneke A. Wilschut, J. Dik F. Habbema, Monique E. van Leerdam, Lieke Hol, Iris Lansdorp-Vogelaar, Ernst J. Kuipers, Marjolein van Ballegooijen
Journal: JNCI Journal of the National Cancer Institute (2011)

Fecal occult blood testing (FOBT) can be adapted to a limited colonoscopy capacity by narrowing the age range or extending the screening interval, by using a more specific test or hemoglobin cutoff level for referral to colonoscopy, and by restricting surveillance colonoscopy. Which of these options is most clinically effective and cost-effective has yet to be established.We used the validated MISCAN-Colon microsimulation model to estimate the number of colonoscopies, costs, and health effects of different screening strategies using guaiac FOBT or fecal immunochemical test (FIT) at various hemoglobin cutoff levels between 50 and 200 ng hemoglobin per mL, different surveillance strategies, and various age ranges. We optimized the allocation of a limited number of colonoscopies on the basis of incremental cost-effectiveness.When colonoscopy capacity was unlimited, the optimal screening strategy was to administer an annual FIT with a 50 ng/mL hemoglobin cutoff level in individuals aged 45-80 years and to offer colonoscopy surveillance to all individuals with adenomas. When colonoscopy capacity was decreasing, the optimal screening adaptation was to first increase the FIT hemoglobin cutoff value to 200 ng hemoglobin per mL and narrow the age range to 50-75 years, to restrict colonoscopy surveillance, and finally to further decrease the number of screening rounds. FIT screening was always more cost-effective compared with guaiac FOBT. Doubling colonoscopy capacity increased the benefits of FIT screening up to 100%.FIT should be used at higher hemoglobin cutoff levels when colonoscopy capacity is limited compared with unlimited and is more effective in terms of health outcomes and cost compared with guaiac FOBT at all colonoscopy capacity levels. Increasing the colonoscopy capacity substantially increases the health benefits of FIT screening.
Erlotinib Prolongs Survival in Pancreatic Cancer by Blocking Gemcitabine-Induced MAPK Signals
Authors: Koji Miyabayashi, Hideaki Ijichi, Dai Mohri, Motohisa Tada, Keisuke Yamamoto, Yoshinari Asaoka, Tsuneo Ikenoue, Keisuke Tateishi, Yousuke Nakai, Hiroyuki Isayama, Yasuyuki Morishita, Masao Omata, Harold L. Moses, Kazuhiko Koike
Journal: Cancer Research (2013)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. Although many regimens have been used for PDAC treatment, the combination of the EGF receptor (EGFR) inhibitor erlotinib with gemcitabine has been the only molecular-targeted drug tested so far that has been superior to gemcitabine alone. The mechanism underlying this effective combinational regimen remains unknown. Here, we show that the combination is superior to gemcitabine alone in blocking progression and prolonging survival in a murine model of PDAC (Kras activation with Tgfbr2 knockout). We found that gemcitabine induced mitogen-activated protein kinase signaling, which was dramatically inhibited by erlotinib even in the Kras-activated PDAC cells in the mouse model. Mechanistic investigations suggested that gemcitabine induces EGFR ligand expression and ERBB2 activation by increasing heterodimer formation with EGFR, thereby maintaining high levels of ERBB2 protein in PDAC cells. Overall, our findings suggest a significant role of ERBB in PDAC treatment.
Walking and primary prevention: a meta-analysis of prospective cohort studies
Authors: M Hamer, Y Chida
Journal: British Journal of Sports Medicine (2007)

Objective: To quantify the association between walking and the risk of cardiovascular disease (CVD) and all-cause mortality in healthy men and women. Data sources: Medline, Cochrane Database of Systematic Reviews, and Web of Science databases were searched to May 2007. Study selection: Prospective epidemiological studies of walking and CVD and all-cause mortality. Results: 18 prospective studies were included in the overall analysis, which incorporated 459 833 participants free from CVD at baseline with 19 249 cases at follow-up. From the meta-analysis the pooled hazard ratio of CVD in the highest walking category compared with the lowest was 0.69, (95% CI 0.61 to 0.77, p&lt;0.001), and 0.68 (0.59 to 0.78, p&lt;0.001) for all-cause mortality. These effects were robust among men and women, although there was evidence of publication biases for the associations with CVD risk. Walking pace was a stronger independent predictor of overall risk compared with walking volume (48% versus 26% risk reductions, respectively). There was also evidence of a dose–response relationship across the highest, intermediate, and lowest walking categories in relation to the outcome measures. Conclusions: The results suggest walking is inversely associated with clinical disease endpoints and largely support the current guidelines for physical activity. The mechanisms that mediate this relationship remain largely unknown and should be the focus of future research.
Severe obstructive sleep apnoea treated with long term nasal continuous positive airway pressure.
Authors: R W Frith, B R Cant
Journal: Thorax (1985)

Seven patients with the severe obstructive sleep apnoea syndrome were treated with nasal continuous positive airway pressure for from three to 22 months. This treatment reversed all symptoms due to the syndrome in every patient and continued to be used in five patients. One patient stopped treatment after eight months and subsequently remained incapacitated and another underwent tracheostomy at the time of transphenoidal hypophysectomy. Nasal continuous positive airway pressure is a safe, non-invasive treatment, which may be used in the presence of cardiac and respiratory failure. It is able fully to reverse upper airway obstruction and can be used at home on a long term basis.
A Randomized, Controlled Crossover Trial of Two Oral Appliances for Sleep Apnea Treatment
Authors: KONRAD E. BLOCH, ANGELO ISELI, JINNONG N. ZHANG, XIAOBIN XIE, VLADIMIR KAPLAN, PAUL W. STOECKLI, ERICH W. RUSSI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Our purpose was to compare the effectiveness and side effects of a novel, single-piece mandibular advancement device (OSA-Monobloc) for sleep apnea therapy with those of a two-piece appliance with lateral Herbst attachments (OSA-Herbst) as used in previous studies. An OSA-Monobloc and an OSA-Herbst with equal protrusion were fitted in 24 obstructive sleep apnea patients unable to use continuous positive airway pressure (CPAP) therapy. After an adaptation period of 156 +/- 14 d (mean +/- SE), patients used the OSA-Monobloc, the OSA-Herbst, and no appliance in random order, using each appliance for 1 wk. Symptom scores were recorded and sleep studies were done at the end of each week. Several symptom scores were significantly improved with both appliances, but to a greater degree with the OSA-Monobloc. Epworth Sleepiness Scale scores were 8.8 +/- 0.7 with the OSA-Herbst, and 8.6 +/- 0.8 with the OSA-Monobloc devices, and 13.1 +/- 0.9 without therapy (p < 0.05 versus both appliances). The apnea/hypopnea index was 8.7 +/- 1.5/h with the OSA-Herbst and 7.9 +/- 1.6/h with the OSA-Monobloc device, and 22.6 +/- 3.1/h without therapy (p < 0.05 versus both appliances). Side effects were mild and of equal prevalence with both appliances. Fifteen patients preferred the OSA-Monobloc, eight patients had no preference, and one patient preferred the OSA-Herbst device (p < 0.008 versus OSA-Monobloc). We conclude that both the OSA-Herbst and the OSA-Monobloc are effective therapeutic devices for sleep apnea. The OSA-Monobloc relieved symptoms to a greater extent than the OSA-Herbst, and was preferred by the majority of patients on the basis of its simple application.
Operative delivery and postnatal depression: a cohort study
Authors: Roshni R Patel, Deirdre J Murphy, Tim J Peters
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To assess the association between elective caesarean section and postnatal depression compared with planned vaginal delivery and whether emergency caesarean section or assisted vaginal delivery is associated with postnatal depression compared with spontaneous vaginal delivery. <b>Design</b> Prospective population based cohort study. <b>Setting</b> ALSPAC (the Avon longitudinal study of parents and children). <b>Participants</b> 14 663 women recruited antenatally with a due date between 1 April 1991 and 31 December 1992. <b>Main outcome measure</b> Edinburgh postnatal depression scale score ≥ 13 at eight weeks postnatal on self completed questionnaire. <b>Results</b> Albeit with wide confidence intervals, there was no evidence that elective caesarean section altered the odds of postnatal depression compared with planned vaginal delivery (adjusted odds ratio 1.06, 95% confidence interval 0.66 to 1.70, P = 0.80). Among planned vaginal deliveries there was similarly little evidence of a difference between women who have emergency caesarean section or assisted vaginal delivery and those who have spontaneous vaginal delivery (1.17, 0.77 to 1.79, P = 0.46, and 0.89, 0.68 to 1.18, P = 0.42, respectively). <b>Conclusions</b> There is no reason for women at risk of postnatal depression to be managed differently with regard to mode of delivery. Elective caesarean section does not protect against postnatal depression. Women who plan vaginal delivery and require emergency caesarean section or assisted vaginal delivery can be reassured that there is no reason to believe that they are at increased risk of postnatal depression.
Impaired Chronotropic and Vasodilator Reserves Limit Exercise Capacity in Patients With Heart Failure and a Preserved Ejection Fraction
Authors: Barry A. Borlaug, Vojtech Melenovsky, Stuart D. Russell, Kristy Kessler, Karel Pacak, Lewis C. Becker, David A. Kass
Journal: Circulation (2006)

Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role.Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180+/-71 versus 455+/-184 seconds; peak oxygen consumption 9.0+/-3.4 versus 14.4+/-3.4 mL x kg(-1) x min(-1); both P<0.001). At matched low-level workload, HFpEF subjects displayed approximately 40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P<0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups.HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.
Abnormalities of Gastric Mucosal Oxygenation in Septic Shock
Authors: BETTINA TEMMESFELD-WOLLBRÜCK, ANTAL SZALAY, KONSTANTIN MAYER, HORST OLSCHEWSKI, WERNER SEEGER, FRIEDRICH GRIMMINGER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Splanchnic mucosal perfusion abnormalities have been implicated in the development of sepsis and multiorgan failure. We employed reflectance spectrophotometry for direct assessment of the microvascular hemoglobin oxygen saturation (HbiO2 ) and hemoglobin concentration (rel Hbconc) in the mucosa of the upper gastrointestinal tract. Owing to the high recording frequency together with a small catchment volume, assessment of spatial heterogeneity is enabled. Results were as follows: In healthy controls (n = 7), mean HbiO2 was 70.3 ± 2.1%, with narrow dispersion and near-Gaussian distribution of the histogram. In patients presenting with hyperdynamic septic shock (n = 15) mean HbiO2 was reduced to 51.0 ± 1.6% in spite of high normal whole-body oxygen delivery, with tailing of the histogram to severely hypoxic values (18.4 % of data < 40%). In parallel, markedly reduced rel Hbconc values were recorded and the standardized intramucosal pH (pHi) was lowered to 7.25 ± 0.01. Short-term infusion of dopexamine (2 μ g/kg/min) caused a significant rise in HbiO2 and rel Hbconc , whereas whole-body oxygen uptake and standardized pHi values were not altered. In conclusion, decreased oxygenation and tissue hemoglobin concentration, with the appearance of severely hypoxic microdomains, were noted in patients with hyperdynamic sepsis, strongly suggesting pronounced microcirculatory disturbances in this compartment. The partial responsiveness of these abnormalities to dopexamine warrants further elucidation. Temmesfeld-Wollbrück B, Szalay A, Mayer K, Olschewski H, Seeger W, Grimminger F. Abnormalities of gastric mucosal oxygenation in septic shock: partial responsiveness to dopexamine.
Compliance of patients and physicians: experience and lessons from tuberculosis-II.
Authors: W Fox
Journal: BMJ (1983)

Fully supervised intermittent chemotherapyThe already obvious clinical need to try to overcome the problems of self administration of medicaments,'6 supported by a scientific basis,4' led us to explore the efficacy and acceptability of intermittent regimens based on twice weekly or once weekly treatment with isoniazid and streptomycin in Madras.6I Subsequently Mitchison and Dickinson43 showed that single pulses of bactericidal drugs could inhibit all division of bacilli for several days.