tbuckley/cabot-search huggingface dataset:
Regulation of Signal Transduction by Reactive Oxygen Species in the Cardiovascular System
Authors: David I. Brown, Kathy K. Griendling
Journal: Circulation Research (2015)

Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species (ROS) in normal physiological signaling has been elucidated. Signaling pathways modulated by ROS are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here, we review the current literature on ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases, including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy, and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis, and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress.
Human Resource and Funding Constraints for Essential Surgery in District Hospitals in Africa: A Retrospective Cross-Sectional Survey
Authors: Margaret E. Kruk, Andreas Wladis, Naboth Mbembati, S. Khady Ndao-Brumblay, Renee Y. Hsia, Moses Galukande, Sam Luboga, Alphonsus Matovu, Helder de Miranda, Doruk Ozgediz, Ana Romàn Quiñones, Peter C. Rockers, Johan von Schreeb, Fernando Vaz, Haile T. Debas, Sarah B. Macfarlane
Journal: PLoS Medicine (2010)

Background There is a growing recognition that the provision of surgical services in low-income countries is inadequate to the need. While constrained health budgets and health worker shortages have been blamed for the low rates of surgery, there has been little empirical data on the providers of surgery and cost of surgical services in Africa. This study described the range of providers of surgical care and anesthesia and estimated the resources dedicated to surgery at district hospitals in three African countries. Methods and Findings We conducted a retrospective cross-sectional survey of data from eight district hospitals in Mozambique, Tanzania, and Uganda. There were no specialist surgeons or anesthetists in any of the hospitals. Most of the health workers were nurses (77.5%), followed by mid-level providers (MLPs) not trained to provide surgical care (7.8%), and MLPs trained to perform surgical procedures (3.8%). There were one to six medical doctors per hospital (4.2% of clinical staff). Most major surgical procedures were performed by doctors (54.6%), however over one-third (35.9%) were done by MLPs. Anesthesia was mainly provided by nurses (39.4%). Most of the hospital expenditure was related to staffing. Of the total operating costs, only 7% to 14% was allocated to surgical care, the majority of which was for obstetric surgery. These costs represent a per capita expenditure on surgery ranging from US$0.05 to US$0.14 between the eight hospitals. Conclusion African countries have adopted different policies to ensure the provision of surgical care in their respective district hospitals. Overall, the surgical output per capita was very low, reflecting low staffing ratios and limited expenditures for surgery. We found that most surgical and anesthesia services in the three countries in the study were provided by generalist doctors, MLPs, and nurses. Although more information is needed to estimate unmet need for surgery, increasing the funds allocated to surgery, and, in the absence of trained doctors and surgeons, formalizing the training of MLPs appears to be a pragmatic and cost-effective way to make basic surgical services available in underserved areas. Please see later in the article for the Editors' Summary
The Genomic, Biochemical, and Cellular Responses of the Retina in Inherited Photoreceptor Degenerations and Prospects for the Treatment of These Disorders
Authors: Alexa N. Bramall, Alan F. Wright, Samuel G. Jacobson, Roderick R. McInnes
Journal: Annual Review of Neuroscience (2010)

The association of more than 140 genes with human photoreceptor degenerations, together with studies of animal models of these monogenic diseases, has provided great insight into their pathogenesis. Here we review the responses of the retina to photoreceptor mutations, including mechanisms of photoreceptor death. We discuss the roles of oxidative metabolism, mitochondrial reactive oxygen species, metabolic stress, protein misfolding, and defects in ciliary proteins, as well as the responses of Müller glia, microglia, and the retinal vasculature. Finally, we report on potential pharmacologic and biologic therapies, the critical role of histopathology as a prerequisite to treatment, and the exciting promise of gene therapy in animal models and in phase 1 trials in humans.
The Cutaneous B-Cell Lymphoma Prognostic Index: A Novel Prognostic Index Derived From a Population-Based Registry
Authors: Benjamin D. Smith, Grace L. Smith, Dennis L. Cooper, Lynn D. Wilson
Journal: Journal of Clinical Oncology (2005)

Purpose Three classification and prognostic systems exist for primary cutaneous B-cell lymphoma (PCBCL). Whereas the WHO classification defines its categories based on histology, both the European Organisation for Research and Treatment of Cancer classification and the conventional staging system consider skin site. We sought to incorporate both histology and skin site into a single prognostic index designed to predict survival in patients with PCBCL. Methods The associations between histology, skin site, and survival were determined using adjusted proportional hazards analysis conducted on 926 patients with PCBCL identified in the Surveillance, Epidemiology, and End Results data, spanning 1973 to 2001. Results Four primary CBCL prognostic index (CBCL-PI) groups were identified. Group IA included indolent histologies involving any skin site. Group IB included diffuse large B-cell histology involving favorable skin sites (head/neck, arm). Group II included diffuse large B-cell histology involving unfavorable skin sites (trunk, legs, disseminated) or immunoblastic large B-cell histology involving favorable skin sites. Group III included immunoblastic large B-cell histology involving unfavorable skin sites. The adjusted mortality hazards ratios were 1.0, 1.3 (95% CI, 0.99 to 1.7), 2.1 (95% CI, 1.6 to 2.7), and 4.5 (95% CI, 2.8 to 7.2) for groups IA/B to III, respectively. The corresponding 5-year relative survivals were 94%, 86%, 60%, and 34%. Conclusion The CBCL-PI identifies adverse combinations of histology and skin site, helping to reconcile differences in current classification and prognostic systems for PCBCL.
Pathogenesis of high-altitude pulmonary oedema: direct evidence of stress failure of pulmonary capillaries
Authors: JB West, GL Colice, YJ Lee, Y Namba, SS Kurdak, Z Fu, LC Ou, O Mathieu-Costello
Journal: European Respiratory Journal (1995)

The pathogenesis of high-altitude pulmonary oedema (HAPE) is disputed. Recent reports show a strong correlation between the occurrence of HAPE and pulmonary artery pressure, and it is known that the oedema is of the high-permeability type. We have, therefore, proposed that HAPE is caused by ultrastructural damage to pulmonary capillaries as a result of stress failure of their walls. However, no satisfactory electron microscopy studies are available in patients with HAPE, and animal models are difficult to find. Madison strain Sprague-Dawley rats show a brisk pulmonary pressure response to acute hypoxia and are susceptible to HAPE. We exposed 13 Madison rats to a pressure of 294 torr for up to 12.5 h, or 4 rats to 236 torr for up to 8 h. Pulmonary arterial or right ventricular systolic pressures measured with a catheter increased from 30.5 +/- 0.5 (SEM) in controls (n = 4) to 48 +/- 2 torr (n = 11). The lungs were fixed for electron microscopy with intravascular glutaraldehyde. Frothy bloodstained fluid was seen in the trachea of three animals. Ultrastructural examination showed evidence of stress failure of pulmonary capillaries, including disruption of the capillary endothelial layer, or all layers of the wall, swelling of the alveolar epithelial layer, red blood cells (RBCs) and oedematous fluid in the alveolar wall interstitium, proteinaceous fluid and RBCs in the alveolar spaces, and fluid-filled protrusions of the endothelium into the capillary lumen.(ABSTRACT TRUNCATED AT 250 WORDS)
Application of the Theory of Heat Exchangers to a Physiological Study of the Goat Placenta
Authors: JOHN H. RANKIN, EDWARD N. PETERSON
Journal: Circulation Research (1969)

The exchange characteristics of the goat placenta were compared to those of several simple models. A technique is described whereby the fetal side of the placenta of the goat near term can be perfused with blood. The ratio of fetal to maternal blood flow was controlled in the range 0.17 to 4.80. The fractions of the maternal and fetal blood flows that did not enter the area of exchange (shunts) were determined by perfusion of the uterine and umbilical circulations with Krebs solution containing dextran and saturated with carbon monoxide and were found to be 36% (SD 3.9%) and 23% (SD 2.2%), respectively. These values were compatible with the shunt values obtained by graphical extrapolation of the data obtained with nitrous oxide and acetylene during perfusion with blood. The N 2 O and C 2 H 2 data showed that the goat placenta has the exchange characteristics of a countercurrent exchanger with extremely unevenly distributed uterine and umbilical flows or those of a concurrent exchanger with moderately uneven distribution of flows. The only available information in the literature on the distribution of flow in this type of placenta indicates that the distribution is moderately uneven.
FRAX program as a method of assessing the risk of osteoporotic fractures in patients with chronic obstructive pulmonary disease
Authors: Ekaterina Kochetova
Journal: European Respiratory Journal (2012)

In patients with COPD have a high risk of osteoporosis.The most convenient tool to detect osteoporosis is a method of estimating the 10-year risk of osteoporotic fractures FRAX, proposed in 2008, JA Kanis. Objective: To explore the practical application of FRAX method to assess the 10-year risk of osteoporotic fractures in patients with COPD. Materials and methods: We examined 108 patients with COPD. The study group comprised men with long smoking history. Mean age 60,2 ± 5,5 years. The study of respiratory function was performed on a multi-type installation «Master-Lab/Jaeger». The study of bone mineral density (BMD) of lumbar spine and proximal femur was performed by X-ray ab-sorbtsiometrii on densitometer «Lunar DPX-NT». Evaluation of ten major osteoporotic fracture risk and the risk of hip fracture was calculated using the computer program FRAX. To calculate the risk methodology used FRAX T-score femoral neck. Results: In assessing the absolute risk of major common fractures associated with osteoporosis, using a computer program FRAX, revealed that the minimal risk of major fractures observed in patients with COPD 2 stage- 3,25, the maximum - in patients with COPD 4 stage -7,4. The maximum risk of hip fracture was observed in patients with COPD 4 stage- 4,5. Established reliable correlation values of ten osteoporotic fracture risk, estimated by the method of FRAX with BMI (r -0,62, p
Is Food Insecurity Associated with HIV Risk? Cross-Sectional Evidence from Sexually Active Women in Brazil
Authors: Alexander C. Tsai, Kristin J. Hung, Sheri D. Weiser
Journal: PLoS Medicine (2012)

Alexander Tsai and colleagues show that in sexually active women in Brazil severe food insecurity with hunger was positively associated with symptoms potentially indicative of sexually transmitted infection and with reduced odds of condom use.
Health benefits of different sport disciplines for adults: systematic review of observational and intervention studies with meta-analysis
Authors: Pekka Oja, Sylvia Titze, Sami Kokko, Urho M Kujala, Ari Heinonen, Paul Kelly, Pasi Koski, Charlie Foster
Journal: British Journal of Sports Medicine (2015)

The aim was to assess the quality and strength of evidence for the health benefits of specific sport disciplines. Electronic search yielded 2194 records and the selection resulted in 69 eligible studies (47 cross-sectional, 9 cohort, 13 intervention studies). 105 comparisons between participation and non-participation groups in 26 different sport disciplines were reported. Moderately strong evidence showed that both running and football improve aerobic fitness and cardiovascular function at rest, and football reduces adiposity. Conditional evidence showed that running benefits metabolic fitness, adiposity and postural balance, and football improves metabolic fitness, muscular performance, postural balance, and cardiac function. Evidence for health benefits of other sport disciplines was either inconclusive or tenuous. The evidence base for the health benefits of specific sports disciplines is generally compromised by weak study design and quality. Future research should address the health effects of different sport disciplines using rigorous research designs.
Orf-induced immunobullous disease: A distinct autoimmune blistering disorder
Authors: Kevin P. White, Daniel C. Zedek, Wain L. White, Eric L. Simpson, Eric Hester, Lynne Morrison, Zelmira Lazarova, Debra Liu, Alessandra Scagliarini, Stephen E. Kurtz, Clifton R. White, Kim B. Yancey, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2007)
Remote Ischemic Preconditioning Protects the Brain Against Injury After Hypothermic Circulatory Arrest
Authors: Hanna A. Jensen, Stavros Loukogeorgakis, Fredrik Yannopoulos, Eija Rimpiläinen, Axel Petzold, Hannu Tuominen, Pasi Lepola, Raymond J. MacAllister, John E. Deanfield, Tuomas Mäkelä, Kirsi Alestalo, Kai Kiviluoma, Vesa Anttila, Victor Tsang, Tatu Juvonen
Journal: Circulation (2011)

Background— Ischemic preconditioning (IPC) is a mechanism protecting tissues from injury during ischemia and reperfusion. Remote IPC (RIPC) can be elicited by applying brief periods of ischemia to tissues with ischemic tolerance, thus protecting vital organs more susceptible to ischemic damage. Using a porcine model, we determined whether RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA). Methods and Results— Twelve piglets were randomized to control and RIPC groups. RIPC was induced in advance of cardiopulmonary bypass by 4 cycles of 5 minutes of ischemia of the hind limb. All animals underwent cardiopulmonary bypass followed by 60 minutes of HCA at 18°C. Brain metabolism and electroencephalographic activity were monitored for 8 hours after HCA. Assessment of neurological status was performed for a week postoperatively. Finally, brain tissue was harvested for histopathological analysis. Study groups were balanced for baseline and intraoperative parameters. Brain lactate concentration was significantly lower ( P &lt;0.0001, ANOVA) and recovery of electroencephalographic activity faster ( P &lt;0.05, ANOVA) in the RIPC group. RIPC had a beneficial effect on neurological function during the 7-day follow-up (behavioral score; P &lt;0.0001 versus control, ANOVA). Histopathological analysis demonstrated a significant reduction in cerebral injury in RIPC animals (injury score; mean [interquartile range]: control 5.8 [3.8 to 7.5] versus RIPC 1.5 [0.5 to 2.5], P &lt;0.001, t test). Conclusions— These data demonstrate that RIPC protects the brain against HCA-induced injury, resulting in accelerated recovery of neurological function. RIPC might be neuroprotective in patients undergoing surgery with HCA and improve long-term outcomes. Clinical trials to test this hypothesis are warranted.
Characterization of acute myeloid leukemia based on levels of global hydroxymethylation
Authors: Leonie I. Kroeze, Mariam G. Aslanyan, Arno van Rooij, Theresia N. Koorenhof-Scheele, Marion Massop, Thomas Carell, Jan B. Boezeman, Jean-Pierre Marie, Constantijn J. M. Halkes, Theo de Witte, Gerwin Huls, Stefan Suciu, Ron A. Wevers, Bert A. van der Reijden, Joop H. Jansen
Journal: Blood (2014)
Recurrent Cancer of the Colon and Rectum
Authors: J. E. Dunphy
Journal: New England Journal of Medicine (1947)

ADVANCES in the treatment of cancer of the colon and rectum consist largely of measures that have extended the amount of resection.1 2 3 4 In early lesions, such radical surgery offers the best assurance of cure. In advanced lesions, it permits the removal of growths that were formerly regarded as totally inoperable. Even when cancer recurs it can be removed by a second attempt at radical surgery. Once a properly executed resection has been done, however, there is a tendency for the surgeon to believe that the die has been cast. Because most recurrences are beyond the scope of surgery, all recurrences . . .
Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children
Authors: David G Addiss, Michael J Beach, Thomas G Streit, Suzanne Lutwick, Fredrick H LeConte, Jack G Lafontant, Allen W Hightower, Patrick J Lammie
Journal: The Lancet (1997)
Does Counseling by Clinicians Improve Physical Activity? A Summary of the Evidence for the U.S. Preventive Services Task Force
Authors: Karen B. Eden, C. Tracy Orleans, Cynthia D. Mulrow, Nola J. Pender, Steven M. Teutsch
Journal: Annals of Internal Medicine (2002)

Purpose: To determine whether counseling adults in primary care settings improves and maintains physical activity levels. Data Sources: The Cochrane Database of Systematic Reviews and Registry of Controlled Trials and the MEDLINE, HealthStar, and Best Evidence databases were searched for papers published from 1994 to March 2002. Study Selection: Controlled trials, case–control studies, and observational studies that examined counseling interventions aimed at increasing physical activity in general primary care populations were reviewed. The researchers included trials in which 1) a patient's primary care clinician performed some of the counseling intervention; 2) behavioral outcomes [physical activity] were reported; and 3) the study was of "good" or "fair" quality, according to criteria developed by the U.S. Preventive Services Task Force. Data Extraction: Data were abstracted on design and execution, quality, providers, patients, setting, counseling intervention, and self-reported physical activity at follow-up. Data Synthesis: Eight trials involving 9054 adults met the inclusion criteria. Among six controlled trials with a usual care control group, the effects of counseling on physical activity were mixed. Because most studies had at least one methodologic limitation, it was difficult to rigorously assess the efficacy of the interventions. More research is needed to clarify the effect, benefits, and potential harms of counseling patients in primary care settings to increase physical activity. Conclusion: Evidence is inconclusive that counseling adults in the primary care setting to increase physical activity is effective.
IgG subclass and light chain distribution of anticardiolipin and anti-DNA antibodies in systemic lupus erythematosus.
Authors: A E Gharavi, E N Harris, M D Lockshin, G R Hughes, K B Elkon
Journal: Annals of the Rheumatic Diseases (1988)

The IgG subclass and light chain distribution of anticardiolipin and anti-DNA antibodies were determined in serum samples from patients with systemic lupus erythematosus. With an enzyme linked immunosorbent assay (ELISA) and mouse monoclonal antibodies to individual subclasses, significant differences in the distributions of IgG2, IgG3, and IgG4 subclasses were observed between anticardiolipin and anti-DNA antibodies. Whereas anti-DNA antibodies were predominantly IgG1 and IgG3, all subclasses of anticardiolipin were detected with a prevalence ranging from 34% (IgG3) to 57% (IgG1). Clinical complications were found slightly more frequently (83%) in patients with sera containing the non or weak complement fixing subclasses (IgG2 and IgG4) than in patients with sera containing complement fixing (IgG1 and IgG3) subclasses (62%). Light chain analysis by ELISA showed a trend towards use of kappa chains for anti-DNA and lambda chains for anticardiolipin antibodies. These findings further emphasise the differences between anti-DNA and anticardiolipin antibodies in terms of their origins and potential mechanisms for producing tissue injury.
Colistin stimulates the activity of neutrophil elastase and Pseudomonas aeruginosa elastase
Authors: A. Jones, H. Elphick, E. Pettitt, M.L. Everard, G.S. Evans
Journal: European Respiratory Journal (2002)

Nonantimicrobial effects of antibiotics may contribute to their activity in the treatment of infective airway disease. The aim of this study was to identify antibiotics used for the treatment of infection in cystic fibrosis that may alter the activity of human neutrophil elastase (HNE) and <i>Pseudomonas aeruginosa</i> elastase (PE). The effect of antibiotics on the activity of purified HNE and PE, and HNE in sputum was assessed using colourimetric and fluorescent substrate assays by kinetic measurements, and by examining the interaction of HNE with inhibitors. Ceftazidime, tobramycin, and gentamycin slightly inhibited purified HNE activity whereas erythromycin and colistin significantly stimulated purified HNE and PE (395 and 557%, respectively). However, only colistin increased HNE activity in sputum (+102%) and was therefore studied in more detail. This increase in activity was not due an interference with the specific inhibition of HNE by α<sub>1</sub>-antitrypsin but colistin was found to reverse the inhibitory effects of small molecular weight molecules like heparin. Colistin increases the activity of human neutrophil elastase and <i>Pseudomonas aeruginosa</i> elastase, two proteases that contribute to the pathogenesis of cystic fibrosis airway disease.
Alexithymia and Symptom Formation
Authors: Michael von Rad
Journal: Psychotherapy and Psychosomatics (1984)

In regard to its clinical descriptive aspects the concept of alexithymia is based on a broad consensus of the investigators. However, with respect to its etiopathogenesis (hereditary, neurophysiological, sociogenic, psychogenic) and its relevance for the formation and maintenance of psychosomatic symptoms, this concept is controversial and unclear. In this context the psychodynamic aspects which are under discussion for the development and maintenance of alexithymic behavior are reported particularly from an object relations point of view. Some resulting principles for a possible psychotherapy of these patients are finally presented.
Cellular theories of aging as related to the liver
Authors: J. Fred Dice
Journal: Hepatology (1985)

The age-associated decjline in function of several organs, including the liver, may be caused by mechanisms operating on the cellular level. Fibroblasts and several other cell types derived from normal individuals have limited lifespans in culture, and several abnormalities described for senescent cultured fibroblasts also apply to hepatocytes and other cell types obtained from aged organisms. Cellular theories of aging can be divided into two broad and overlapping categories: (a) those that view cell death as an actively programmed developmental process, and (b) those that consider cellular aging to result from a passive accumulation of errors in macromolecules. These theories are not necessarily mutually exclusive, and many of the phenotypic changes in senescent hepatocytes, fibroblasts and other cells are compatible with several different theories. The challenge for the future is to distinguish primary causes from secondary consequences of cellular aging so that rational attempts to intervene in the aging process are possible.