tbuckley/cabot-search huggingface dataset:
Orchestrated Information Transfer Underlying Leukocyte Endothelial Interactions
Authors: Klaus Ebnet, Eric P. Kaldjian, Arthur O. Anderson, Stephen Shaw
Journal: Annual Review of Immunology (1996)

The specificity and efficiency of leukocyte binding to endothelial cells (ECs) depends on coordinated information transfer from the underlying tissue to endothelium and from there to the leukocyte. We address three distinct information-transfer points in this system: 1, How does the leukocyte read information from the EC? This process is best accounted for by the paradigm of a multi-step adhesion cascade optimized for rapid information readout; it consists of primary adhesion (rolling/tethering), triggering, and strong adhesion. Recent studies with T cells, monocytes, and eosinophils confirm the generality of the paradigm. The concept of primary adhesion has been expanded to involve not only the selectins, but also certain integrins; furthermore, it depends on receptor concentration on leukocyte microvilli. 2. What information from the underlying tissue does the EC transform into signals for the leukocytes? And what rules govern that process? We illustrate the principles with chemokines, believed to participate in the triggering step. The endothelium displays chemokines either (a) directly by "posting" them from other cells or (b) by integrating a variety of tissue and environmental signals and "relaying" that information by producing its own chemokines and surface adhesion molecules. The rules for this endothelial transduction include specificity coupled with redundancy, amplification, synergy, and coordinated induction of ensembles of molecules. Finally, 3. How does the relevant information reach the endothelium? Simple diffusion is sufficient to deliver signals from cells close to the vessel. However, longer range soluble mediator transport appears to be facilitated by fiber bundles, particularly those ensheathed by fibroblastic reticular cells in the lymph node.
Evidence of methodological bias in hospital standardised mortality ratios: retrospective database study of English hospitals
Authors: M. A Mohammed, J. J Deeks, A. Girling, G. Rudge, M. Carmalt, A. J Stevens, R. J Lilford
Journal: BMJ (2009)

<b>Objective</b> To assess the validity of case mix adjustment methods used to derive standardised mortality ratios for hospitals, by examining the consistency of relations between risk factors and mortality across hospitals. <b>Design</b> Retrospective analysis of routinely collected hospital data comparing observed deaths with deaths predicted by the Dr Foster Unit case mix method. <b>Setting</b> Four acute National Health Service hospitals in the West Midlands (England) with case mix adjusted standardised mortality ratios ranging from 88 to 140. <b>Participants</b> 96 948 (April 2005 to March 2006), 126 695 (April 2006 to March 2007), and 62 639 (April to October 2007) admissions to the four hospitals. <b>Main outcome measures</b> Presence of large interaction effects between case mix variable and hospital in a logistic regression model indicating non-constant risk relations, and plausible mechanisms that could give rise to these effects. <b>Results</b> Large significant (P≤0.0001) interaction effects were seen with several case mix adjustment variables. For two of these variables—the Charlson (comorbidity) index and emergency admission—interaction effects could be explained credibly by differences in clinical coding and admission practices across hospitals. <b>Conclusions</b> The Dr Foster Unit hospital standardised mortality ratio is derived from an internationally adopted/adapted method, which uses at least two variables (the Charlson comorbidity index and emergency admission) that are unsafe for case mix adjustment because their inclusion may actually increase the very bias that case mix adjustment is intended to reduce. Claims that variations in hospital standardised mortality ratios from Dr Foster Unit reflect differences in quality of care are less than credible.
Cellular profiles of induced sputum in children with stable cystic fibrosis: comparison with BAL
Authors: N. Reinhardt, C.I.U. Chen, D. Loppow, T. Schink, I. Kleinau, R.A. Jörres, U. Wahn, H. Magnussen, K.P. Paul
Journal: European Respiratory Journal (2003)

Neutrophil-dominated endobronchial inflammation is a major characteristic of cystic fibrosis (CF) and there is increasing demand for easy-to-perform noninvasive monitoring for prediction and intervention. Fourteen stable paediatric CF patients (8–17 yrs; mean forced expiratory volume in one second 86.7% of the predicted value) were investigated once by fractional bronchoalveolar lavage (BAL) and by sputum induction on three occasions, 2–6 weeks apart. Sputum was induced by consecutive 10‐min inhalations of 3, 4 and 5% saline. CFsputum cellular profiles were compared with BAL fluid cell counts and samples from age-matched healthy children, and between different time points to assess reproducibility. Adequate sputum was recovered on &gt;95% of occasions. In all sputum fractions, CF patients showed higher neutrophil counts than healthy children. Neutrophil percentages were highest in the first BAL fraction (median 92%), followed by sputum, in which the percentages decreased in consecutive fractions (72, 66 and 64%), whereas counts were lowest in the pooled BAL fraction (53%). Increasing percentages of macrophages mirrored the decreases in neutrophil percentage. Results of sputum induction at different time points in the CF patients showed good reproducibility and nonoverlap with counts from healthy children. In conclusion, the results of sputum induction in children with mild stable cystic fibrosis adequately describe airway inflammation by providing cellular profiles with lower relative neutrophil counts than in the first (“bronchial”) bronchoalveolar lavage fraction and higher relative neutrophil counts than in subsequent pooled (“more peripheral”) bronchoalveolar lavage fractions.
Killing the messenger: new insights into nonsense-mediated mRNA decay
Authors: Peter H. Byers
Journal: Journal of Clinical Investigation (2002)

A When the accession numbers are entered at the National Center for Biotechnology Information home site (http://www.ncbi.nlm.nih.gov/)they will provide direct links to nucleotide and protein sequences as well as references to the identification of these genes.B UPF3B (XM_016123) and UPF3X (NM_023010) appear to represent two additional copies of the UPF3 gene.How they differ in function from the UPF3A gene and transcript is not understood.C The web address for WormBase, the database for C. elegans genome information, is http://www.wormbase.org/.EST, expressed sequence tag.
Pulmonary complications in patients with haematological malignancies treated at a respiratory ICU
Authors: S Ewig, A Torres, R Riquelme, M El-Ebiary, M Rovira, E Carreras, A Rano, A Xaubet
Journal: European Respiratory Journal (1998)

Patients with haematological malignancies developing severe pulmonary complications have a poor outcome, especially after bone-marrow transplantation (BMT). We studied the aetiology, the yield of different diagnostic tools, as well as the outcome and prognostic factors in the corresponding population admitted to our respiratory intensive care unit (RICU). Overall, 89 patients with haematological malignancies and pulmonary complications treated within a 10 yr period were included. The underlying malignancies were predominantly acute leukaemia and chronic myeloid leukaemia (66/89, 74%). Fifty-two of 89 (58%) patients were bone marrow recipients. An aetiological diagnosis could be obtained in 61/89 (69%) of cases. The aetiology was infectious in 37/89 (42%) and noninfectious in 24/89 (27%). Blood cultures and cytological examinations of bronchoalveolar lavage fluid were the diagnostic tools with the highest yield (13/43 (30%) and 13/45 (29%) positive results, respectively). Necropsy results were coincident with results obtained during the lifetime in 43% of cases with infectious and 60% with noninfectious aetiologies. Overall mortality was 70/89 (79%), and 47/52 (90%) in transplant recipients. The requirement of mechanical ventilation, BMT, and an interval &lt;90 days of BMT prior to ICU admission were independent adverse prognostic factors. The outcome in this patient population was uniformly poor. It was worst in bone marrow recipients developing pulmonary complications &lt;90 days after transplantation and requiring mechanical ventilation. Decisions about intensive care unit admission and mech-anical ventilation should seriously consider the dismal prognosis of these patients.
Cholesterol-Lowering Drugs and Colorectal Cancer Incidence in a Large United States Cohort
Authors: Eric J. Jacobs, Carmen Rodriguez, Kerri A. Brady, Cari J. Connell, Michael J. Thun, Eugenia E. Calle
Journal: JNCI Journal of the National Cancer Institute (2006)

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, account for most cholesterol-lowering drug use in the United States. A recent large case-control study reported that use of statins for more than 5 years was associated with a 47% reduction in risk of colorectal cancer. No other large studies have examined this association. We examined the association between use of cholesterol-lowering drugs and colorectal cancer incidence among 132,136 men and women in the Cancer Prevention Study II Nutrition Cohort. We identified 815 incident cases of colorectal cancer among study participants during follow-up from the date of completion of a study questionnaire in 1997 through August 31, 2001. Current use of cholesterol-lowering drugs was not associated with colorectal cancer incidence (multivariable adjusted rate ratio [RR] = 1.03, 95% confidence interval [CI] = 0.85 to 1.26). Current use of cholesterol-lowering drugs for 5 years or more was also not associated with colorectal cancer incidence (multivariable adjusted RR = 1.09, 95% CI = 0.83 to 1.43). Our results do not support the hypothesis that statin use strongly reduces risk of colorectal cancer. However, we cannot rule out a small reduction in risk or an effect associated with only specific types or doses of statins.
New e-records system leads to 20% drop in emergency department performance at Addenbrooke's
Authors: A. O'Dowd
Journal: BMJ (2014)

The first hospital trust in the United Kingdom to implement a new electronic patient records system has experienced a 20% drop in the performance of its emergency department, as well as other serious problems.

The new eHospital system was launched at Addenbrooke’s and Rosie Hospitals in Cambridge in October, promising improvements to the care of patients. But so far the system has experienced what the local clinical commissioning group (CCG) has called “significant problems” that have affected the hospital’s performance and local GPs.

Cambridge University Hospitals NHS Foundation Trust, which runs the two hospitals, has given reassurances that it made allowances for delays while the new system was being implemented and said that it was treating concerns over the potential effect on the safety of patients seriously.

The eHospital system, which went live on 26 October, is designed to improve the quality of care for patients by ensuring that clinical staff can access relevant patient information wherever they are using handheld devices with bespoke software designed by clinicians. The trust has worked with two partners over 18 months to implement the system, which was provided by a company called Epic, while Hewlett Packard provided the …
Differences in the management of shoulder pain between primary and secondary care in Europe: time for a consensus
Authors: D G Kassimos, G Panayi, D A W M van der Windt
Journal: Annals of the Rheumatic Diseases (2004)

We read with great interest the articles of Van der Windt and Bouter1 and Hay et al .2 There is no doubt that the study of Hay et al is well designed and has practical implications. They showed that physiotherapy or subacromial joint injection are equally effective for shoulder pain. This is new evidence as, so far, there has been little evidence to support the effectiveness of any common intervention for shoulder pain.3 However, the definition of “shoulder pain” illustrates the practical problem in diagnosis that general practitioners and hospital specialists face in routine clinical practice. We agree that the positive outcome for physiotherapy may reflect the increased contact time between physiotherapist and patient or the better understanding of the anatomical problem by the physiotherapist. The differences in management and in the effectiveness of physiotherapy by the British compared with the Dutch may also represent a cultural difference between the expectations and beliefs of patients in the two countries. It is likely that physiotherapy departments could be overloaded with referrals from primary care doctors if they are always the first next step in the pathway of managing …
Chemotherapy Induces Tumor Clearance Independent of Apoptosis
Authors: Jennifer L. Guerriero, Dara Ditsworth, Yongjun Fan, Fangping Zhao, Howard C. Crawford, Wei-Xing Zong
Journal: Cancer Research (2008)

Abstract Dysregulation of apoptosis is associated with the development of human cancer and resistance to anticancer therapy. The ultimate goal of cancer treatment is to selectively induce cancer cell death and overcome drug resistance. A deeper understanding of how a given chemotherapy affects tumor cell death is needed to develop strategically designed anticancer agents. Here, we use a xenograft mouse tumor system generated from genetically defined cells deficient in apoptosis to examine the involvement of multiple forms of cell death induced by cyclophosphamide (CP), a DNA alkylating agent commonly used in chemotherapy. We find that although apoptosis facilitates tumor regression, it is dispensable for complete tumor regression as other forms of cell death are activated. Sporadic necrosis is observed in both apoptosis-competent and deficient tumors evident by tumor cell morphology, extracellular release of high mobility group box 1 protein, and activation of innate immune cells in CP-treated tumors. Our findings indicate that in apoptosis-deficient tumors, necrosis may play a fundamental role in tumor clearance by stimulating the innate immune response. [Cancer Res 2008;68(23):9595–600]
Investigations on health-related properties of two sepiolite samples.
Authors: B Bellmann, H Muhle, H Ernst
Journal: Environmental Health Perspectives (1997)

Published i.p. injection studies have shown different biological behavior of different sepiolite samples. There was no evidence for carcinogenic potential of sepiolite from Vicalvaro, Spain, whereas a high tumor incidence was reported for sepiolite from Finland. The low biological activity of the sepiolite from Vicalvaro, compared to the Finnish sample, could be caused by low in vivo persistence or by the short length of the fibers, or both. In this study a further sepiolite sample, obtained as a commercial sample originating from China, was investigated. This sample contained a higher fraction of fibers longer than 5 microns, comparable to the Finnish sepiolite sample. The fraction of fibers with a length > 5 microns was 0.12 and 2.2% for the Vicalvaro and Chinese sepiolite, respectively. For the fiber fraction longer than 8 microns, the corresponding values were 0.0045 and 0.82%. The in vivo persistence of the sepiolite samples from China and Vicalvaro was analyzed after intratracheal instillation of 2 mg in female Wistar rats. Fiber retention in the lungs was analyzed by transmission electron microscopy at different sacrifice dates up to 12 months after application. For the Vicalvaro sepiolite, a splitting of fiber bundles was found during retention time in the lung. Therefore, no half-time of the fiber clearance could be calculated from the number of fibers. The decrease of the calculated retained fiber mass was faster for the Vicalvaro sepiolite (T1/2 = 89 days) compared to the Chinese sepiolite (T1/2 = 129 days). For 2 or 3 rats per group, at sacrifice date 12 months after i.p. injection, the lung was investigated by histopathology. The main difference between both treatment groups was a more pronounced fibrotic response in the Chinese sepiolite-treated rats compared to those treated with Vicalvaro sepiolite. It is concluded that both the higher fraction of long sepiolite fibers and the slower elimination rate of the fiber mass in the Chinese sample were important factors for the different biological reaction in comparison with Vicalvaro sepiolite.
Pharmacotherapy and Family-Focused Treatment for Adolescents With Bipolar I and II Disorders: A 2-Year Randomized Trial
Authors: David J. Miklowitz, Christopher D. Schneck, Elizabeth L. George, Dawn O. Taylor, Catherine A. Sugar, Boris Birmaher, Robert A. Kowatch, Melissa P. DelBello, David A. Axelson
Journal: American Journal of Psychiatry (2014)

Intensive family-focused treatment together with pharmacotherapy proved no more effective than pharmacotherapy with brief psychotherapy in hastening recovery or delaying recurrence of bipolar disorder among adolescents.
The Global Burden of Ischemic Heart Disease in 1990 and 2010
Authors: Andrew E. Moran, Mohammad H. Forouzanfar, Gregory A. Roth, George A. Mensah, Majid Ezzati, Abraham Flaxman, Christopher J.L. Murray, Mohsen Naghavi
Journal: Circulation (2014)

Ischemic heart disease (IHD) burden consists of years of life lost from IHD deaths and years of disability lived with 3 nonfatal IHD sequelae: nonfatal acute myocardial infarction, angina pectoris, and ischemic heart failure. Our aim was to estimate the global and regional burden of IHD in 1990 and 2010.Global and regional estimates of acute myocardial infarction incidence and angina and heart failure prevalence by age, sex, and world region in 1990 and 2010 were estimated based on data from a systematic review and nonlinear mixed-effects meta-regression methods. Age-standardized acute myocardial infarction incidence and angina prevalence decreased globally between 1990 and 2010; ischemic heart failure prevalence increased slightly. The global burden of IHD increased by 29 million disability-adjusted life-years (29% increase) between 1990 and 2010. About 32.4% of the growth in global IHD disability-adjusted life-years between 1990 and 2010 was attributable to aging of the world population, 22.1% was attributable to population growth, and total disability-adjusted life-years were attenuated by a 25.3% decrease in per capita IHD burden (decreased rate). The number of people living with nonfatal IHD increased more than the number of IHD deaths since 1990, but >90% of IHD disability-adjusted life-years in 2010 were attributable to IHD deaths.Globally, age-standardized acute myocardial infarction incidence and angina prevalence have decreased, and ischemic heart failure prevalence has increased since 1990. Despite decreased age-standardized fatal and nonfatal IHD in most regions since 1990, population growth and aging led to a higher global burden of IHD in 2010.
Gly82Ser Polymorphism of the Receptor for Advanced Glycation End Products Is Associated with an Increased Risk of Gastric Cancer in a Chinese Population
Authors: Haijuan Gu, Li Yang, Qingmin Sun, Bo Zhou, Naping Tang, Rihong Cong, Ying Zeng, Bin Wang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: It has been shown that the expression of the receptor for advanced glycation end products (RAGE) is closely associated with invasion and metastasis in gastric cancer. A Gly82Ser polymorphism in exon 3 of RAGE gene was identified and thought to have an effect on the functions of its protein. Therefore, the goal of the present study was to investigate whether the polymorphism is involved in the development or progression of gastric cancer. Experimental Design: In the hospital-based case-control study, the RAGE genotypes were determined using PCR-RFLP in 566 individuals (283 gastric cancer patients and 283 age- and sex-matched controls). Results: The distribution of genotype was significantly different between cases and controls (P = 0.038). Compared with the wild-type 82Gly/Gly carriers, subjects with the variant genotypes (82Gly/Ser and 82Ser/Ser) had a significantly higher risk of gastric cancer (adjusted odds ratio, 1.47; 95% confidence interval, 1.05-2.06). Moreover, the elevated gastric cancer risk was especially evident in younger individuals (ages ≤58 years), nonsmokers, and rural subjects. Further analyses revealed that the variant genotypes were associated with adjacent organ invasion in the subanalysis of gastric cancer patients. Conclusions: Our findings indicate that the RAGE Gly82Ser polymorphism may confer not only an increased risk of gastric cancer but also with invasion of gastric cancer in the Chinese population.
SERIAL RENAL CLEARANCES IN DOGS WITH NEPHROGENIC AND SPONTANEOUS HYPERTENSION
Authors: J. Stamler, L. N. Katz, S. Rodbard
Journal: The Journal of Experimental Medicine (1949)

Evidence is presented on the occurrence of spontaneous hypertension in dogs. All dogs with spontaneous hypertension exhibited normal renal plasma flow and glomerular filtration rate. Clearances on nephrogenic hypertensive dogs revealed that some exhibited normal kidney function, while others had significant depression of renal plasma flow and glomerular filtration rate. In the latter, the filtration fraction may or may not be elevated. Serial renal clearances were done at intervals on 3 dogs with spontaneous hypertension during their 3rd year of known hypertension. They exhibited no tendency to develop impaired renal function in the face of prolonged benign hypertension. Serial renal clearances on nephrogenic hypertensive dogs revealed no tendency for kidney function to become progressively impaired. This was true, whether the immediate postoperative clearance values were normal or depressed. It was also true regardless of the duration of the hypertension. It is suggested that mechanisms other than elevated blood pressure per se operate to produce progressive kidney damage and impairment of renal function. No tendency was revealed over the course of a year or more for the kidney function to improve in Goldblatt dogs exhibiting depressed clearances immediately postoperatively. This is interpreted as evidence against the postoperative development in persistently hypertensive Goldblatt dogs of a renal collateral circulation sufficient to augment significantly effective renal blood flow. Pathological studies on 2 dogs with spontaneous hypertension revealed slight to moderate chronic focal lesions in the kidneys, and bilateral adrenal cortical adenomatous hyperplasia. Both lesions may have no pathogenetic significance. In accord with previous observations, autopsies on 3 Goldblatt dogs revealed minimal renal changes in one, and unilateral kidney atrophy with contralateral hypertrophy in the 2 others. The adrenals were normal. In general, data on renal clearances showed correlation with postmortem kidney findings. However, normal renal clearances are found in the presence of anatomically abnormal kidneys. The findings in canine spontaneous and nephrogenic hypertension are compared and contrasted with data obtained in human essential hypertension. Pathogenetic relationships are discussed.