tbuckley/cabot-search huggingface dataset:
Identification of craniofacial risk factors for obstructive sleep apnoea using three-dimensional MRI
Authors: L. Chi, F-L. Comyn, N. Mitra, M.P. Reilly, F. Wan, G. Maislin, L. Chmiewski, M.D. Thorne-FitzGerald, U.N. Victor, A.I. Pack, R.J. Schwab
Journal: European Respiratory Journal (2011)

The alteration of craniofacial structures has been associated with obstructive sleep apnoea (OSA). We hypothesised that: 1) a smaller mandible is a risk factor for OSA; and 2) the previously observed inferiorly positioned hyoid bone in apnoeics is associated with enlarged tongue volume. This is a case-control study using three-dimensional magnetic resonance imaging cephalometry. 55 apneics and 55 controls were matched for age, sex and race. The analysis was stratified by sex and controlled for age, race, height, neck visceral fat, skeletal type and tongue volume. We found that a 1-sd increase in mandibular length and depth were associated with decreased risk of sleep apnoea (OR 0.52, 95% CI 0.28-0.99 and OR 0.46, 95% CI 0.23-0.91, respectively) in males but not in females. Greater hyoid-to-nasion (OR 2.64, 95% CI 1.19-5.89 in males and OR 5.01, 95% CI 2.00-12.52 in females) and supramentale-to-hyoid (OR 2.39, 95% CI 1.12-5.14) in males and OR 3.38, 95% CI 1.49-7.68 in females) distances were associated with increased risk of OSA. The difference for hyoid position between apnoeics and controls was lost after controlling for tongue volume. Enlargement of tongue is likely to be the pathogenic factor for inferior-posterior positioning of hyoid. A small and shallow mandible is an independent risk factor for OSA in males but not in females.
Approaches to Sudden Death from Coronary Heart Disease
Authors: BERNARD LOWN, MARSHALL WOLF
Journal: Circulation (1971)

Sudden cardiac death (SCD) continues unabated. Coronary care units, while effective in lowering hospital mortality, cannot significantly reduce SCD which occurs primarily outside the hospital and accounts for the majority of deaths from coronary heart disease (CHD). In view of the frequent precipitous nature of SCD, only a program which identifies and protects the victim prior to the event can hope to be successful in preventing the majority of SCD. Since it is likely that SCD is due to an arrhythmia, drug prophylaxis might prove effective. In view of the toxicity of currently available agents, it is mandatory to preselect a population at highest risk before embarking on a drug trial. Ventricular premature beats (VPB) may identify subjects susceptible to SCD. Epidemiologic and physiologic information on VPB is reviewed, and proposals are made for studies designed to establish the usefulness of VPB as a risk factor for SCD.
Global Molecular Effects of Tocilizumab Therapy in Rheumatoid Arthritis Synovium
Authors: Julie Ducreux, Patrick Durez, Christine Galant, Adrien Nzeusseu Toukap, Benoît Van den Eynde, Frédéric A. Houssiau, Bernard R. Lauwerys
Journal: Arthritis & Rheumatology (2013)

Objective To investigate the global molecular effects of tocilizumab (TCZ) in comparison with methotrexate (MTX) treatment in synovial biopsy tissue obtained from patients with previously untreated rheumatoid arthritis (RA) before therapy (T0) and 12 weeks after the initiation of therapy (T12), and to compare the results with previous gene expression data obtained in synovial biopsy tissue from adalimumab (ADA)– and rituximab (RTX)–treated patients with RA. Methods Paired synovial biopsy samples were obtained at T0 and T12 from the affected knee of TCZ‐treated RA patients and MTX‐treated RA patients. Gene expression studies were performed using GeneChip Human Genome U133 Plus 2.0 microarrays, and confirmatory quantitative real‐time reverse transcription–polymerase chain reaction experiments were performed on selected transcripts. The effects of TCZ and MTX on synovial cell populations and histologic characteristics were assessed by immunohistochemistry. Results Gene expression studies showed that blockade of the interleukin‐6 receptor (IL‐6R) gene ( IL6R ) using TCZ induced a significant decrease in the expression of numerous chemokine and T cell activation genes in the RA synovium. These effects strongly correlated with the molecular effects of MTX and RTX therapy on RA synovial tissue, but differed from the molecular changes induced by ADA (decreased expression of genes involved in cell proliferation). Conclusion The molecular similarities between the effects of TCZ, RTX, and MTX therapies in the RA synovium indicate that B cell– and IL‐6 –dependent pathways play synergistic roles in the pathogenesis of the disease, in particular through activation of T cell responses. Moreover, these results open perspectives for the individualization of therapeutic decisions, based on a better knowledge of the synovial molecular effects of each type of RA therapy.
Steroids, non-steroidal anti-inflammatory drugs, and sigmoid diverticular abscess perforation in rheumatic conditions
Authors: S Mpofu
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Corticosteroids and non-steroidal anti-inflammatory drugs are widely used for the treatment of rheumatic conditions, but their gastrointestinal damage significantly limits their use. Sigmoid diverticular abscess perforation (SDAP) is a very serious complication of diverticular disease. <b>Objective:</b> To determine the aetiology of large bowel SDAP in rheumatic conditions. <b>Methods:</b> 64 patients with SPAD and 320 controls from a similar geographical area and of similar socioeconomic status were studied. <b>Results:</b> The results showed that independently of rheumatic diagnosis corticosteroid treatment is strongly associated with SDAP (OR 31.9 (95% CI 6.4 to 159.2; p&lt;0.001), and non-steroidal anti-inflammatory drugs only weakly associated (OR 1.8 (95% CI 0.96 to 3.4); p = 0.069). A rheumatic diagnosis is also strongly associated with the development of SDAP (OR 3.5 (95% CI 1.9 to 6.7); p&lt;0.001). <b>Conclusions:</b> SDAP has serious implications for patients and consumes many healthcare resources. Patients and physicians should be warned of this potential complication.
The Effect of Topically Applied Corticosteroids on the Dinitrochlorobenzene sensitivity Reaction in Guinea-Pigs
Authors: A. F. Heald, F. Ridgway
Journal: British Journal of Dermatology (1969)

Journal Article The Effect of Topically Applied Corticosteroids on the Dinitrochlorobenzene sensitivity Reaction in Guinea‐Pigs Get access A. F. Heald, A. F. Heald E. R. Squibb & sons Ltd., International Development Laboratories, Moreton. Wirral. Cheshire Search for other works by this author on: Oxford Academic Google Scholar F. Ridgway F. Ridgway E. R. Squibb & sons Ltd., International Development Laboratories, Moreton. Wirral. Cheshire Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 1, 1 January 1969, Page 76, https://doi.org/10.1111/j.1365-2133.1969.tb15925.x Published: 01 January 1969
Cause-Specific Mortality in the Unionized U.S. Trucking Industry
Authors: Francine Laden, Jaime E. Hart, Thomas J. Smith, Mary E. Davis, Eric Garshick
Journal: Environmental Health Perspectives (2007)

Occupational and population-based studies have related exposure to fine particulate air pollution, and specifically particulate matter from vehicle exhausts, to cardiovascular diseases and lung cancer.We have established a large retrospective cohort to assess mortality in the unionized U.S. trucking industry. To provide insight into mortality patterns associated with job-specific exposures, we examined rates of cause-specific mortality compared with the general U.S. population.We used records from four national trucking companies to identify 54,319 male employees employed in 1985. Cause-specific mortality was assessed through 2000 using the National Death Index. Expected numbers of all and cause-specific deaths were calculated stratifying by race, 10-year age group, and calendar period using U.S. national reference rates. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated for the entire cohort and by job title.As expected in a working population, we found a deficit in overall and all-cancer mortality, likely due to the healthy worker effect. In contrast, compared with the general U.S. population, we observed elevated rates for lung cancer, ischemic heart disease, and transport-related accidents. Lung cancer rates were elevated among all drivers (SMR = 1.10; 95% CI, 1.02-1.19) and dockworkers (SMR = 1.10; 95% CI, 0.94-1.30); ischemic heart disease was also elevated among these groups of workers [drivers, SMR = 1.49 (95% CI, 1.40-1.59); dockworkers, SMR = 1.32 (95% CI, 1.15-1.52)], as well as among shop workers (SMR = 1.34; 95% CI, 1.05-1.72).In this detailed assessment of specific job categories in the U.S. trucking industry, we found an excess of mortality due to lung cancer and ischemic heart disease, particularly among drivers.
High mutation rates have driven extensive structural polymorphism among human Y chromosomes
Authors: Sjoerd Repping, Saskia K M van Daalen, Laura G Brown, Cindy M Korver, Julian Lange, Janet D Marszalek, Tatyana Pyntikova, Fulco van der Veen, Helen Skaletsky, David C Page, Steve Rozen
Journal: Nature Genetics (2006)
miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma
Authors: Nataliya Razumilava, Steve F. Bronk, Rory L. Smoot, Christian D. Fingas, Nathan W. Werneburg, Lewis R. Roberts, Justin L. Mott
Journal: Hepatology (2011)

It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of miR-25 in culture sensitized cells to apoptotic death. Computational analysis identified the TRAIL Death Receptor-4 (DR4) as a potential novel miR-25 target, and this prediction was confirmed by immunoblot, cell staining, and reporter assays.These data implicate elevated miR-25 levels in the control of tumor cell apoptosis in cholangiocarcinoma. The identification of the novel miR-25 target DR4 provides a mechanism by which miR-25 contributes to evasion of TRAIL-induced cholangiocarcinoma apoptosis.
Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis
Authors: Sonya L Heltshe, Christopher H Goss, Valeria Thompson, Scott D Sagel, Don B Sanders, Bruce C Marshall, Patrick A Flume
Journal: Thorax (2015)

<h3>Background</h3> Treatment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) varies widely with no consensus on management practices or best indicators of therapeutic success. To design trials evaluating PEx treatment factors, we characterise the heterogeneity of PEx care in adults and paediatrics, and correlate it with measures of clinical response including short-term and long-term lung function changes, change in symptom severity score and time to next intravenous antibiotic therapy. <h3>Methods</h3> Data were used from a prospective observational study of patients with CF ≥10 years of age enrolled at six sites between 2007 and 2010. All were started on intravenous antibiotics for a clinically diagnosed PEx. Analysis of variance, logistic and Cox regression were used to examine the association of treatment factors with short-term and long-term clinical response. <h3>Results</h3> Of 123 patients with CF (60% women, aged 23.1±10.2 years), 33% experienced &lt;10% relative improvement in FEV<sub>1</sub> during treatment, which was associated with failing to recover baseline lung function 3 months after treatment (OR=7.8, 95% CI 1.9 to 31.6, p=0.004) and a longer time to next intravenous antibiotic (HR=0.48, 95% CI 0.27 to 0.85, p=0.011). Symptom improvement was observed but was not associated with subsequent lung function or time to next antibiotic therapy, which had a median recurrence time of 143 days. <h3>Conclusions</h3> Immediate symptomatic or respiratory response to PEx treatment did not have a clear relationship with subsequent outcomes such as lung function or intravenous antibiotic-free interval. These results can inform future research of treatment regimens for PEx in terms of interventions and outcome measures. <h3>Trial registration</h3> NCT00788359 (www.clinicaltrials.gov).
Phase I/II Trial of Preoperative Oxaliplatin, Docetaxel, and Capecitabine With Concurrent Radiation Therapy in Localized Carcinoma of the Esophagus or Gastroesophageal Junction
Authors: David R. Spigel, F. Anthony Greco, Anthony A. Meluch, Cassie M. Lane, Cynthia Farley, James R. Gray, Bobby L. Clark, Howard A. Burris, John D. Hainsworth
Journal: Journal of Clinical Oncology (2010)

Purpose Preoperative chemoradiotherapy is a primary treatment option for patients with resectable esophageal cancer. Combination regimens using newer agents may improve patient outcomes. This multicenter community-based phase I/II trial examined a modern triplet regimen comprised of oxaliplatin, docetaxel, and capecitabine (ODC) combined with radiation therapy (RT). Patients and Methods The primary end point was the pathologic complete response (pCR) rate. Eligibility criteria included resectable stage I to III cancer of the mid-/distal-esophagus or gastroesophageal junction, measurable disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Treatment included oxaliplatin 40 mg/m 2 , docetaxel 20 mg/m 2 (intravenous, weekly × 5); capecitabine 1,000 mg/m 2 orally twice daily on days 1 to 7, 15 to 21, and 29 to 35; and concurrent RT (45 Gy). Resection was performed during weeks 9 to 12. ODC and RT safety was determined in a phase I portion (n = 10) preceding phase II. Results Fifty-nine patients were enrolled (September 2005 to February 2008; phase I/cohort 1, 10 patients; phase I/cohort 2/phase II, 49 patients). Baseline characteristics included median age of 63 years; 84% male; ECOG PS 0 and 1, 51% and 49%, respectively; adenocarcinoma and squamous cell, 69% and 18%, respectively; stage I, II, and III, 12%, 41%, and 45%, respectively. Phase I revealed no dose-limiting toxicity. Responses: pCR rate, 49%; objective response rate, 61% (24 complete and six partial responses); stable disease, 6%; and progressive disease, 2%. Sixty-nine percent of patients underwent surgery. Survival: median follow-up, 116 weeks; median disease-free survival (DFS) and overall survival (OS) were 16.3 and 24.1 months, respectively. Two-year DFS and OS were 45.1% and 52.2%, respectively. Most common (≥ 5%) grade 3 to 4 nonhematologic toxicities were anorexia (20%), dehydration (16%), diarrhea (8%), dysphagia (10%), esophagitis (20%), fatigue (12%), hyperglycemia (6%), nausea (16%), pulmonary symptoms (14%), sepsis (6%), and vomiting (16%). All other grade 3 to 4 hematologic and nonhematologic toxicities were uncommon (&lt; 5%). Conclusion Preoperative ODC plus RT is active and relatively safe in patients with locoregional esophageal cancer. Importantly, this therapy can be administered within 8 weeks. This regimen warrants additional study in this setting and in combination with newer biologic agents.
Molecular Targets in Melanoma from Angiogenesis to Apoptosis
Authors: Jeffrey A. Sosman, Igor Puzanov
Journal: Clinical Cancer Research (2006)

Abstract Angiogenesis is a hallmark of melanoma progression. Antiangiogenic agents have been infrequently tested in patients with advanced melanoma. Experience with most other cancers suggests that single-agent application of angiogenic inhibitors is unlikely to have substantial clinical antitumor activity in melanoma. It is more likely that combinations of antiangiogenic agents with either chemotherapy or other targeted therapy will be needed to produce significant clinical benefit. In melanoma, numerous cellular pathways important to cell proliferation, apoptosis, or metastases have recently been shown to be activated. Activation occurs through specific mutations (B-RAF, N-RAS, and PTEN) or changes in expression levels of various proteins (PTEN, BCL-2, NF-κB, CDK2, and cyclin D1). Agents that block these pathways are rapidly entering the clinical setting, including RAF inhibitors (sorafenib), mitogen-activated protein kinase inhibitors (PD0325901), mammalian target of rapamycin inhibitors (CCI-779), and farnesyl transferase inhibitors (R115777) that inhibit N-RAS and proteasome inhibitors (PS-341) that block activation of nuclear factor-κB (NF-κB). It will be a challenge to evaluate these agents alone, in combination with each other, or with chemotherapy in patients with melanoma. Trials with large populations of biologically ill-defined tumors run the risk of missing clinical antitumor activity that is important for a particular yet-to-be-defined subset of patients. To rationally and optimally develop these targeted agents, it will be critical to adequately test for the presence of the presumed cellular target in tumor specimens and the effect of therapy on the proposed target (biological response). Investigators in this field will need to carefully plan these trials so that at the end of the day, we learn from both the failures and successes of targeted therapy.
Intact β-Adrenergic Response and Unmodified Progression Toward Heart Failure in Mice With Genetic Ablation of a Major Protein Kinase A Phosphorylation Site in the Cardiac Ryanodine Receptor
Authors: Nancy A. Benkusky, Craig S. Weber, Joseph A. Scherman, Emily F. Farrell, Timothy A. Hacker, Manorama C. John, Patricia A. Powers, Héctor H. Valdivia
Journal: Circulation Research (2007)

Increased phosphorylation of the cardiac ryanodine receptor (RyR)2 by protein kinase A (PKA) at the phosphoepitope encompassing Ser2808 has been advanced as a central mechanism in the pathogenesis of cardiac arrhythmias and heart failure. In this scheme, persistent activation of the sympathetic system during chronic stress leads to PKA "hyperphosphorylation" of RyR2-S2808, which increases Ca2+ release by augmenting the sensitivity of the RyR2 channel to diastolic Ca2+. This gain-of-function is postulated to occur with the unique participation of RyR2-S2808, and other potential PKA phosphorylation sites have been discarded. Although it is clear that RyR2 is among the first proteins in the heart to be phosphorylated by beta-adrenergic stimulation, the functional impact of phosphorylation in excitation-contraction coupling and cardiac performance remains unclear. We used gene targeting to produce a mouse model with complete ablation of the RyR2-S2808 phosphorylation site (RyR2-S2808A). Whole-heart and isolated cardiomyocyte experiments were performed to test the role of beta-adrenergic stimulation and PKA phosphorylation of Ser2808 in heart failure progression and cellular Ca2+ handling. We found that the RyR2-S2808A mutation does not alter the beta-adrenergic response, leaves cellular function almost unchanged, and offers no significant protection in the maladaptive cardiac remodeling induced by chronic stress. Moreover, the RyR2-S2808A mutation appears to modify single-channel activity, although modestly and only at activating [Ca2+]. Taken together, these results reveal some of the most important effects of PKA phosphorylation of RyR2 but do not support a major role for RyR2-S2808 phosphorylation in the pathogenesis of cardiac dysfunction and failure.
Successful chemical cholecystectomy: a laparoscopic guided technique.
Authors: A Cuschieri, A A Abd el Ghany, M P Holley
Journal: Gut (1989)

A laparoscopic guided technique of percutaneous chemical destruction of the gall bladder is described. The procedure entails the creation of a percutaneous access cholecystostomy for stone removal/fragmentation. After endoscopic occlusion of the cystic duct, the alkali corrosive, sodium carbonate was instilled into the gall bladder for 10-15 minutes. The treatment was applied in 11 animals with three deaths because of technical mishaps and eight survivors, in five of which a histologically confirmed complete destruction of the gall bladder (chemical cholecystectomy) was achieved without damage to the rest of the biliary tract or liver parenchyma.
Multiple Drug Resistance in Osteogenic Sarcoma: INT0133 From the Children's Oncology Group
Authors: Cindy L. Schwartz, Richard Gorlick, Lisa Teot, Mark Krailo, Zhengjia Chen, Allen Goorin, Holcombe E. Grier, Mark L. Bernstein, Paul Meyers
Journal: Journal of Clinical Oncology (2007)

Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma.From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp-positive disease and were compared with patients with P-gp-negative disease.P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494-negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1-positive versus JSB-1-negative tumors (P = .65). OS for patients with C-494-positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494-negative tumors (P = .61).Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.
Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data
Authors: Stella G Muthuri, Sudhir Venkatesan, Puja R Myles, Jo Leonardi-Bee, Tarig S A Al Khuwaitir, Adbullah Al Mamun, Ashish P Anovadiya, Eduardo Azziz-Baumgartner, Clarisa Báez, Matteo Bassetti, Bojana Beovic, Barbara Bertisch, Isabelle Bonmarin, Robert Booy, Victor H Borja-Aburto, Heinz Burgmann, Bin Cao, Jordi Carratala, Justin T Denholm, Samuel R Dominguez, Pericles A D Duarte, Gal Dubnov-Raz, Marcela Echavarria, Sergio Fanella, Zhancheng Gao, Patrick Gérardin, Maddalena Giannella, Sophie Gubbels, Jethro Herberg, Anjarath L Higuera Iglesias, Peter H Hoger, Xiaoyun Hu, Quazi T Islam, Mirela F Jiménez, Amr Kandeel, Gerben Keijzers, Hossein Khalili, Marian Knight, Koichiro Kudo, Gabriela Kusznierz, Ilija Kuzman, Arthur M C Kwan, Idriss Lahlou Amine, Eduard Langenegger, Kamran B Lankarani, Yee-Sin Leo, Rita Linko, Pei Liu, Faris Madanat, Elga Mayo-Montero, Allison McGeer, Ziad Memish, Gokhan Metan, Auksė Mickiene, Dragan Mikić, Kristin G I Mohn, Ahmadreza Moradi, Pagbajabyn Nymadawa, Maria E Oliva, Mehpare Ozkan, Dhruv Parekh, Mical Paul, Fernando P Polack, Barbara A Rath, Alejandro H Rodríguez, Elena B Sarrouf, Anna C Seale, Bunyamin Sertogullarindan, Marilda M Siqueira, Joanna Skręt-Magierło, Frank Stephan, Ewa Talarek, Julian W Tang, Kelvin K W To, Antoni Torres, Selda H Törün, Dat Tran, Timothy M Uyeki, Annelies Van Zwol, Wendy Vaudry, Tjasa Vidmar, Renata T C Yokota, Paul Zarogoulidis, Jonathan S Nguyen-Van-Tam
Journal: The Lancet Respiratory Medicine (2014)