tbuckley/cabot-search huggingface dataset:
Erythropoietin Selectively Attenuates Cytokine Production and Inflammation in Cerebral Ischemia by Targeting Neuronal Apoptosis
Authors: Pia Villa, Paolo Bigini, Tiziana Mennini, Davide Agnello, Teresa Laragione, Alfredo Cagnotto, Barbara Viviani, Marina Marinovich, Anthony Cerami, Thomas R. Coleman, Michael Brines, Pietro Ghezzi
Journal: The Journal of Experimental Medicine (2003)

Ischemic brain injury resulting from stroke arises from primary neuronal losses and by inflammatory responses. Previous studies suggest that erythropoietin (EPO) attenuates both processes. Although EPO is clearly antiapoptotic for neurons after experimental stroke, it is unknown whether EPO also directly modulates EPO receptor (EPO-R)–expressing glia, microglia, and other inflammatory cells. In these experiments, we show that recombinant human EPO (rhEPO; 5,000 U/kg body weight, i.p.) markedly reduces astrocyte activation and the recruitment of leukocytes and microglia into an infarction produced by middle cerebral artery occlusion in rats. In addition, ischemia-induced production of the proinflammatory cytokines tumor necrosis factor, interleukin 6, and monocyte chemoattractant protein 1 concentration is reduced by &amp;gt;50% after rhEPO administration. Similar results were also observed in mixed neuronal-glial cocultures exposed to the neuronal-selective toxin trimethyl tin. In contrast, rhEPO did not inhibit cytokine production by astrocyte cultures exposed to neuronal homogenates or modulate the response of human peripheral blood mononuclear cells, rat glial cells, or the brain to lipopolysaccharide. These findings suggest that rhEPO attenuates ischemia-induced inflammation by reducing neuronal death rather than by direct effects upon EPO-R–expressing inflammatory cells.
Compliance With Evidence-Based Guidelines and Interhospital Variation in Mortality for Patients With Severe Traumatic Brain Injury
Authors: Aaron J. Dawes, Greg D. Sacks, H. Gill Cryer, J. Peter Gruen, Christy Preston, Deidre Gorospe, Marilyn Cohen, David L. McArthur, Marcia M. Russell, Melinda Maggard-Gibbons, Clifford Y. Ko
Journal: JAMA Surgery (2015)

Compliance with evidence-based guidelines in traumatic brain injury (TBI) has been proposed as a marker of hospital quality. However, the association between hospital-level compliance rates and risk-adjusted clinical outcomes for patients with TBI remains poorly understood.To examine whether hospital-level compliance with the Brain Trauma Foundation guidelines for intracranial pressure monitoring and craniotomy is associated with risk-adjusted mortality rates for patients with severe TBI.All adult patients (N = 734) who presented to a regional consortium of 14 hospitals from January 1, 2009, through December 31, 2010, with severe TBI (ie, blunt head trauma, Glasgow Coma Scale score of <9, and abnormal intracranial findings from computed tomography of the head). Data analysis took place from December 2013 through January 2015. We used hierarchical mixed-effects models to assess the association between hospital-level compliance with Brain Trauma Foundation guidelines and mortality rates after adjusting for patient-level demographics, severity of trauma (eg, mechanism of injury and Injury Severity Score), and TBI-specific variables (eg, cranial nerve reflexes and findings from computed tomography of the head).Hospital-level risk-adjusted inpatient mortality rate and hospital-level compliance with Brain Trauma Foundation guidelines for intracranial pressure monitoring and craniotomy.Unadjusted mortality rates varied by site from 20.0% to 50.0% (median, 42.6; interquartile range, 35.5-46.2); risk-adjusted rates varied from 24.3% to 56.7% (median, 41.1; interquartile range, 36.4-47.8). Overall, only 338 of 734 patients (46.1%) with an appropriate indication underwent placement of an intracranial pressure monitor and only 134 of 335 (45.6%) underwent craniotomy. Hospital-level compliance ranged from 9.6% to 65.2% for intracranial pressure monitoring and 6.7% to 76.2% for craniotomy. Despite widespread variation in compliance across hospitals, we found no association between hospital-level compliance rates and risk-adjusted patient outcomes (Spearman ρ = 0.030 [P = .92] for ICP monitoring and Spearman ρ = -0.066 [P = .83] for craniotomy).Hospital-level compliance with evidence-based guidelines has minimal association with risk-adjusted outcomes in patients with severe TBI. Our results suggest that caution should be taken before using compliance with these measures as independent quality metrics. Given the complexity of TBI care, outcomes-based metrics, including functional recovery, may be more accurate than current process measures at determining hospital quality.
The Relevance of Adler's Psychology to Present-Day Theory
Authors: KURT A. ADLER
Journal: American Journal of Psychiatry (1970)

Adler's Individual Psychology is an ego psychology. One of its bases is adaptation leading to goal-directed striving for mastery or superiority. Heredity, instincts, and environment are not seen as determining personality; they are only the building materials the child used to construct his unique personality. Man therefore strives freely for his progress rather than being a slave to his instincts. Another basis of Adler's psychology is man's social nature, which totally permeates his thinking, feeling, willing, and acting.
Early Decline in Cancer Antigen 125 as a Surrogate for Progression-Free Survival in Recurrent Ovarian Cancer
Authors: Chee K. Lee, Michael Friedlander, Chris Brown, Val J. Gebski, Alexander Georgoulopoulos, Ignace Vergote, Sandro Pignata, Nicoletta Donadello, Barbara Schmalfeldt, Rémy Delva, Mansoor Raza Mirza, Philippe Sauthier, Eric Pujade-Lauraine, Sarah J. Lord, R. John Simes
Journal: JNCI Journal of the National Cancer Institute (2011)

We used data from 886 patients from the CAELYX in Platinum Sensitive Ovarian Patients (CALYPSO) trial, recruited between April 2005 and September 2007, to examine the role of early decline in cancer antigen 125 (CA125) and early tumor response as prognostic factors and surrogates for superiority of treatment with carboplatin–pegylated liposomal doxorubicin (CPLD) compared with carboplatin–paclitaxel (CP) in a landmark analysis. Progression-free survival (PFS) was estimated by Kaplan–Meier analyses. We used univariate and multivariable Cox proportional hazards analyses to assess early decline and early response as surrogates for CPLD treatment benefit compared with CP. All statistical tests were two-sided. Early decline (defined as rate of CA125 decrease of at least 50% per month) was associated with improved PFS (adjusted hazard ratio [HR] for progression = 0.81, 95% confidence interval [CI] = 0.67 to 0.97 ,P = .02) but early response (complete or partial responses) was not. CPLD was associated with improved PFS compared with CP (HR = 0.82, 95% CI = 0.69 to 0.96, P = .01). However, fewer CPLD patients had an early decline (161 [37.4%] vs 233 [51.2%], P < .001) or an early response (146 [33.9%] vs 176 [38.7%], P = .14) compared with CP patients. The PFS for CPLD patients did not change statistically significantly after adjustment for early decline (adjusted HR = 0.80, 95% CI = 0.68 to 0.94, P = .007). These findings are opposite to what would be expected if these markers were good surrogates for treatment benefit.
Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates
Authors: Chang Z. Chun, Sukhbir Kaur, Ganesh V. Samant, Ling Wang, Kallal Pramanik, Maija K. Garnaas, Keguo Li, Lyndsay Field, Debabrata Mukhopadhyay, Ramani Ramchandran
Journal: Blood (2008)
Maternal B vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis in Apc1638N mouse offspring
Authors: E. D. Ciappio, Z. Liu, R. S. Brooks, J. B. Mason, R. T. Bronson, J. W. Crott
Journal: Gut (2011)

<h3>Objective</h3> Variations in the intake of folate are capable of modulating colorectal tumorigenesis; however, the outcome appears to be dependent on timing. This study sought to determine the effect of altering folate (and related B vitamin) availability during in-utero development and the suckling period on intestinal tumorigenesis. <h3>Design</h3> Female wildtype mice were fed diets either mildly deficient, replete or supplemented with vitamins B<sub>2</sub>, B<sub>6</sub>, B<sub>12</sub> and folate for 4 weeks before mating to Apc<sup>1638N</sup> males. Females remained on their diet throughout pregnancy and until weaning. After weaning, all Apc<sup>1638N</sup> offspring were maintained on replete diets for 29 weeks. <h3>Results</h3> At 8 months of age tumour incidence was markedly lower among offspring of supplemented mothers (21%) compared with those of replete (59%) and deficient (55%) mothers (p=0.03). Furthermore, tumours in pups born to deficient dams were most likely to be invasive (p=0.03). The expression of <i>Apc, Sfrp1, Wif1 and Wnt5a</i>—all of which are negative regulatory elements of the <i>Wnt</i> signalling cascade—in the normal small intestinal mucosa of pups decreased with decreasing maternal B vitamin intake, and for <i>Sfrp1</i> this was inversely related to promoter methylation. β-Catenin protein was elevated in offspring of deficient dams. <h3>Conclusions</h3> These changes indicate a de-repression of the <i>Wnt</i> pathway in pups of deficient dams and form a plausible mechanism by which maternal B vitamin intake modulates tumorigenesis in offspring. These data indicate that maternal B vitamin supplementation suppresses, while deficiency promotes, intestinal tumorigenesis in <i>Apc<sup>1638N</sup></i> offspring.
Exogenous female sex steroid hormones and risk of asthma and asthma-like symptoms: a cross sectional study of the general population
Authors: P Lange
Journal: Thorax (2001)

Background-Recent evidence suggests a role for hormonal factors in the aetiology of asthma.Methods-Data from a large study of women selected from the general population were used to relate treatment with oral hormonal contraceptives (OCP) and postmenopausal hormone replacement therapy (HRT) to the following asthma indicators: self-reported asthma, wheezing, cough at exertion, and use of medication for asthma.The study sample comprised 1536 premenopausal and 3016 postmenopausal women who participated in the third round of the Copenhagen City Heart Study in 1991-4.A total of 377 women were taking OCP (24.5% of premenopausal women) and 458 were on HRT (15.2% of postmenopausal women).Results-In premenopausal women 4.8% reported having asthma.The prevalence of self-reported asthma, wheeze, use of asthma medication, and cough at exertion was not significantly related to use of OCP.In postmenopausal women the prevalence of self-reported asthma was 6.2%.A weak but consistent association was observed between HRT and self-reported asthma (OR 1.42 (95% CI 0.95 to 2.12)), wheeze (OR 1.29 (95% CI 1.02 to 1.64)), cough at exertion (OR 1.34 (95% CI 1.01 to 1.77)), and use of asthma medication (OR 1.45 (95% CI 0.97 to 2.18)).Conclusions-In this study of the general population no relationship was found between the use of OCP and asthma.Although an association was observed between HRT and asthma and asthmalike symptoms, this was relatively weak and it is concluded that there is no necessity to change present prescription practice.
Chemoprevention of Precancerous Gastric Lesions With Antioxidant Vitamin Supplementation: A Randomized Trial in a High-Risk Population
Authors: Martyn Plummer, Jorge Vivas, Gladys Lopez, Juan Carlos Bravo, Simon Peraza, Elsa Carillo, Elsa Cano, Denis Castro, Olga Andrade, Victor Sánchez, Rita Garcia, Eva Buiatti, Claude Aebischer, Silvia Franceschi, Walter Oliver, Nubia Muñoz
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundGastric cancer is one of the most common malignancies worldwide. Histopathologic studies have identified a sequence of changes in the gastric mucosa that mark the slow progression from normal tissue to carcinoma. Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables could be a protective factor against this disease. This effect may be mediated through antioxidant vitamins.
Government seeks suitable sites for proton beam therapy
Authors: A. O'Dowd
Journal: BMJ (2009)

A new drive to boost the effectiveness of cancer treatment in the United Kingdom by using an advanced form of radiotherapy has been launched.

The Department of Health is inviting hospitals to bid to provide proton beam therapy―a type of radiotherapy in which a cyclotron produces a beam of protons.

Proton beam therapy can treat tumours without damaging vital organs because it targets the malignancy precisely, providing better dose distribution than conventional radiotherapy. It is particularly suitable for children.

The department has asked the NHS’s national specialised commissioning team to identify possible providers of proton beam services in England, though the services could be accessible to the whole of …
The endothelium-dependent effect of RTEF-1 in pressure overload cardiac hypertrophy: role of VEGF-B
Authors: Ming Xu, Yi Jin, Qinhui Song, Jiaping Wu, Melissa J. Philbrick, Brittany L. Cully, Xiaojin An, Lin Guo, Feng Gao, Jian Li
Journal: Cardiovascular Research (2010)

Related transcription enhancer factor-1 (RTEF-1) has previously been demonstrated to play an important role in both endothelial cells and cardiomyocytes. However, the function of RTEF-1 in the communication between these two adjacent cell types has not been elucidated. We have found that endothelium-specific RTEF-1 transgenic mice (VE-Cad/RTEF-1) developed significant cardiac hypertrophy after transverse aortic constriction surgery, as evidenced by an increased ratio of heart weight to tibia length, enlarged cardiomyocyte size, thickened left ventricular wall and elevated expression of hypertrophic gene markers, with up-regulation of vascular endothelial growth factor B (VEGF-B). Additionally, VEGF-B was increased in endothelial cells from VE-Cad/RTEF-1 mice, as well as in endothelial cells with forced RTEF-1 expression (HMEC-1/RTEF-1), and coincidentally decreased when RTEF-1 was deficient in HMEC-1. Using chromatin immunoprecipitation and luciferase assays, we found that RTEF-1 increased VEGF-B promoter activity through a direct interaction. Hypertrophy-associated genes and protein synthesis were up-regulated in cardiomyocytes that were incubated with conditioned medium from HMEC-1/RTEF-1 and the endothelial cells of VE-Cad/RTEF-1 mice. This effect could be abrogated by treating the myocytes with VEGF-B small interfering RNA and extracellular signal-regulated kinase 1/2 inhibitor. Our data demonstrated that increased RTEF-1 in endothelial cells upregulates VEGF-B, which is able to stimulate hypertrophic genes in cardiomyocytes. These results suggest that the RTEF-1-driven increase of VEGF-B plays an important role in communication between the endothelium and myocardium.
Gefitinib and irinotecan in patients with fluoropyrimidine-refractory, irinotecan-naive advanced colorectal cancer: a phase I–II study
Authors: I. Chau, D. Cunningham, T. Hickish, A. Massey, L. Higgins, R. Osborne, N. Botwood, A. Swaisland
Journal: Annals of Oncology (2007)
Prevalence and Determinants of Type 2 Diabetes Among Filipino-Americans in the Houston, Texas Metropolitan Statistical Area
Authors: Luceli C. Cuasay, Eun Sul Lee, Philip P. Orlander, Lyn Steffen-Batey, Craig L. Hanis
Journal: Diabetes Care (2001)

OBJECTIVE—The few available studies suggest that Filipino-Americans have an increased risk for developing type 2 diabetes. The purpose of this study was to determine the prevalence of previously diagnosed type 2 diabetes and its major risk factors among Filipino-Americans. RESEARCH DESIGN AND METHODS—A cross-sectional survey was conducted in the Houston, Texas, metropolitan statistical area between September 1998 and March 2000. The convenience sample included 831 Filipino-American participants aged 20–74 years. The major risk factors assessed were age, sex, family history of diabetes, socioeconomic status, obesity (BMI &amp;gt;30), physical inactivity, acculturation, region of birth and, in women, history of gestational diabetes and delivery of a baby weighing &amp;gt;9 lb. RESULTS—Overall prevalence was estimated to be 16.1% (95% CI 13.5–18.7). Multivariate logistic regression analyses identified independent risk factors: increasing age from ages 35–44 years (odds ratio [OR] 5.6, 95% CI 1.5–20.5) to 65–74 years (34.2, 7.2–163.0); male sex (1.8, 1.1–32.1); family history of diabetes (4.7, 2.6–8.5); obesity (3.6, 1.4–9.0); region of birth, Mindanao (3.2, 1.3–7.7); and, among women, gestational diabetes (21.7, 6.7–69.7) and low income (5.3, 1.4–20.2). CONCLUSIONS—The study observed a high prevalence of type 2 diabetes and supports earlier studies suggesting that Filipinos are at higher risk for type 2 diabetes than the U.S. non-Hispanic white population.
Immunofluorescent Examination of Biopsies from Long-Term Renal Allografts
Authors: J. J. McPhaul, F. J. Dixon, L. Brettschneider, T. E. Starzl
Journal: New England Journal of Medicine (1970)

Immunofluorescent examination of open renal biopsies revealed clear-cut glomerular localization of immunoglobulins not related clearly to the quality of donor-recipient histocompatibility in 19 of 34 renal allografts. The biopsies were obtained 18 to 31 months after transplantations primarily from related donors with a variable quality of histocompatibility match. IgG was the predominant immunoglobulin class fixed in 13 biopsies, and IgM in six. The pattern of immunoglobulin deposition was linear, connoting anti-GBM antibody in four of the 19; it was granular and discontinuous, connoting antigen–antibodycomplex deposits, in 13. An immune process may affect glomeruli of renal allografts by mechanisms comparable to those that cause glomerulonephritis in native kidneys. The transplant glomerulonephritis may represent a persistence of the same disease that originally destroyed the host kidneys or the consequence of a new humoral antibody response to allograft antigens.
Introducing MEDWatch. A new approach to reporting medication and device adverse effects and product problems
Authors: D. A. Kessler
Journal: JAMA (1993)

UNFORTUNATELY, many health professionals do not think to report adverse events that might be associated with medications or devices to the Food and Drug Administration (FDA) or to the manufacturer. That needs to change, and the FDA is taking steps to encourage that to happen. Reports from health professionals of adverse events or product quality problems are essential to ensure the safety of drugs, biologicals, medical devices, and other products regulated by the FDA once they are introduced into the US market. Even the large, well-designed clinical trials that are conducted to gain pre-market approval cannot uncover every problem that can come to light once a product is widely used. A new drug application, for example, typically includes safety data on several hundred to several thousand patients. If an adverse event occurs in perhaps one in 5000 or even one in 1000 users, it could be missed in clinical trials
The Diagnosis of the Acute Abdomen in Rhyme
Authors: J. F de Wolff
Journal: BMJ (2009)

Many a junior doctor has requested an opinion from a surgical registrar on a patient with a suspected acute abdominal disorder. The invariable reply is: “Get an abdominal x ray and a blood gas, and I’ll come and put a hand on their tummy.”

The author of this little work, written entirely in rhyme, would have disapproved. It first appeared in 1947. In those days preceding abdominal computed tomography he lamented: “We culture this, we plant out that with care / And on the places with hope we daily stare / We test the blood for complement-fixation …
Six month radiological and physiological outcomes in severe acute respiratory syndrome (SARS) survivors
Authors: C K Ng
Journal: Thorax (2004)

The long term physiological and radiological outcomes of SARS survivors and their possible determinants are uncertain.SARS survivors in a follow up clinic in a regional hospital underwent high resolution computed tomography (HRCT) of the thorax and lung function tests 6 months after admission to hospital. The associations between the clinical and demographic data of the patients and the physiological and radiological outcomes were examined.Fifty seven patients took part in the study. Lung function abnormalities were detected in 43 patients (75.4%), with restrictive defects (n = 16) being most common (28.1%). Radiological abnormalities of any degree were detected in 43 patients (75.4%). Only the use of pulse corticosteroids was associated with the presence of CT abnormalities (p = 0.043, OR 6.65, 95% CI 1.06 to 41.73).Physiological and radiological abnormalities are still present in a considerable proportion of SARS survivors at 6 months.
Arterial Stiffness Is Associated With Cardiovascular, Renal, Retinal, and Autonomic Disease in Type 1 Diabetes
Authors: Simone Theilade, Maria Lajer, Frederik Persson, Christel Joergensen, Peter Rossing
Journal: Diabetes Care (2012)

In patients with type 1 diabetes, we investigated the association between arterial stiffness and diabetes complications.This was a cross-sectional study including 676 Caucasian patients with type 1 diabetes (374 [55%] men, aged 54 ± 13 years [mean ± SD]) and 51 nondiabetic controls (28 [55%] men, aged 47 ± 13 years). Aortic pulse wave velocity (PWV) was measured with SphygmoCor (AtCor Medical, Sydney, Australia) for 635 patients and all 51 controls.PWVs (mean ± SD) in patients and controls were 10.4 ± 3.4 and 7.6 ± 1.9 m/s, respectively (P < 0.001). After multivariate adjustment, PWV correlated with age, diabetes duration, urinary albumin excretion rate, heart rate, and blood pressure (P < 0.05 for all). ANCOVA was used for comparisons between groups and adjusted for gender, age, estimated glomerular filtration rate, heart rate, HbA(1c), and 24-h mean arterial pressure. PWVs in normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 9.5 ± 3.2, 11.0 ± 3.6, and 11.4 ± 3.0 m/s, respectively (adjusted P < 0.001). PWV in patients with previous cardiovascular disease, versus patients without, was 12.1 ± 3.5 vs. 10.0 ± 3.2 m/s, respectively (adjusted P < 0.001). PWVs in patients with high (≥140/90 mmHg) versus intermediate (130-40/80-89 mmHg) and low (<130/80 mmHg) blood pressure were 11.8 ± 3.6, 10.0 ± 3.0, and 9.8 ± 3.3 m/s, respectively (adjusted P < 0.001). Furthermore, PWV increased with increasing degree of retinopathy: 8.0 ± 2.5 m/s (nil), 10.0 ± 2.8 m/s (simplex), 12.1 ± 3.5 m/s (proliferative), and 12.7 ± 2.4 m/s (blind), respectively (adjusted P < 0.001). Finally, PWV increased with abnormal heart rate variability: 11.5 ± 3.3 m/s vs. 10.1 ± 3.1 m/s (borderline) and 8.1 ± 2.1 m/s (normal) (adjusted P = 0.027).Arterial stiffness increased with presence and duration of type 1 diabetes. Furthermore, PWV increased with all the investigated diabetes complications (cardiovascular, renal, retinal, and autonomic disease) independently of other risk factors.
The Epithelial-derived Cytokines TSLP, IL-33, and IL-25 Converge on OX40L to Elicit Peanut Allergy and Anaphylaxis in Mice
Authors: D.K. Chu, A. Llop-Guevara, T.D. Walker, K. Flader, C.L. Moore, S. Goncharova, J. Boudreau, W. Khan, M.R. Comeau, A.L. Budelsky, R. Kolbeck, A.A. Humbles, M. Jordana
Journal: Journal of Allergy and Clinical Immunology (2011)
Want a friend? Get a dog
Authors: L. Farrell
Journal: BMJ (2011)

“I have a list,” he said. As inflammatory opening gambits go, it’s hard to beat.

Osler advised equanimity as the second most important medical virtue, next to sarcasm. So over many years I have cultivated a tranquil demeanour, which the casual observer might misinterpret as apathy. I sat back in my chair, closed my eyes, counted to ten, let peace come dropping slow upon linnet’s wings; a mote of dust floated down. Accordingly, my response …