tbuckley/cabot-search huggingface dataset:
Flavonoids Influence Monocytic GTPase Activity and Are Protective in Experimental Allergic Encephalitis
Authors: Jerome J.A. Hendriks, Jacqueline Alblas, Susanne M.A. van der Pol, Eric A.F. van Tol, Christine D. Dijkstra, Helga E. de Vries
Journal: The Journal of Experimental Medicine (2004)

In the chronic disabling disease multiple sclerosis (MS), migration of monocytes across the blood-brain barrier is a crucial step in the formation of new lesions in the central nervous system (CNS). Infiltrating monocyte-derived macrophages secrete inflammatory mediators such as oxygen radicals, which contribute to axonal demyelination and damage, resulting in neurological deficits. Flavonoids are compounds occurring naturally in food, which scavenge oxygen radicals and have antiinflammatory properties. To investigate whether they might suppress clinical symptoms in MS, we treated rats sensitized for acute and chronic experimental allergic encephalomyelitis, an experimental model of MS, with flavonoids. We demonstrated that the flavonoid luteolin substantially suppressed clinical symptoms and prevented relapse when administered either before or after disease onset. Luteolin treatment resulted in reduced inflammation and axonal damage in the CNS by preventing monocyte migration across the brain endothelium. Luteolin influenced migration by modulating the activity of Rho GTPases, signal transducers involved in transendothelial migration. Oral administration of luteolin also significantly reduced clinical symptoms.
Heart rate response to "off-road" running events in female athletes.
Authors: U Creagh, T Reilly, A M Nevill
Journal: British Journal of Sports Medicine (1998)

Despite the growing popularity of off-road running events, little information is available about the physiological stress of such activities. The demands of such events are unique in terms of the rough surface of the terrain encountered as well as the underfoot vegetation and the gradient.The aim of this study was to investigate the physiological response of female athletes, as measured by heart rate, to three common off-road running events: cross country running (n = 15), fell running (n = 20), and orienteering (n = 25).Heart rate responses were recorded during cross country and fell races, and orienteering by means of short range radiotelemetry. Road running (n = 21) was also studied as a reference.The mean heart rates for each event varied with the differing demands of the terrain. The highest (182 (10) beats/minute; mean (SD)) was for road running and the lowest (172 (10) beats/minute) for orienteering. Orienteering evoked a significantly more variable response than all other events (F4,100 = 112.4; p<0.01), with a range of 44 beats/minute (142-186 beats/minute) in the heart rate. This may be due to both the variability of the terrain and the additional technical aspect of this sport. There was a positive trend in the slope of the regression lines of heart rate against time for both road and cross country running, which was not evident in the fell runners or the orienteers. The latter events demonstrated no consistent pattern.It is concluded that running off-road elicits a heart rate response that varies with the altering demands of surface, vegetation, and gradient.
The Prognostic Significance of Indium-111–Capromab Penetide
Authors: D.B. Sodee, P.F. Faulhaber, A.D. Nelson, G. Bakale
Journal: Journal of Clinical Oncology (2004)

all continue to strive to see that patients get both the chemotherapeutic intervention that they need, which is the emphasis of your article, and also the expert preoperative counseling and surgery they need as well.
EFFICIENCY AND SAFETY OF MECHANICAL VENTILATION WITH A HEAT AND MOISTURE EXCHANGER CHANGED ONCE A WEEK
Authors: Bernard Paluch
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The cost of mechanical ventilation (MV) is high. Efforts to reduce this cost, as long as they are not detrimental for the patients, are needed. MV with heat and moisture exchangers (HME) changed every 48 h is safe, efficient, and cost-effective. Preliminary reports suggest that the life span of these filters may be prolonged. We determined prospectively whether a hygroscopic and hydrophobic HME (Hygrobac-Dar; Mallinckrodt) provided safe and efficient heating and humidification of the inspired gases when changed only once a week. Patients who were considered to require mechanical ventilation for more than 48 h were included in the study. HMEs were initially set for 7 d. Efficient airway heating and humidification were assessed by clinical parameters (number of tracheal suctionings and instillations required, peak airway pressures) and hygrometric measurements performed by psychrometry. Resistance was measured from Day 0 to Day 7. Bacterial colonization of circuits and HMEs was studied. A total of 377 days ...
QUANTITATIVE ASPECTS OF THE RELEASE OF LEUKOCYTE PYROGEN FROM RABBIT BLOOD INCUBATED WITH ENDOTOXIN
Authors: P. A. Murphy
Journal: The Journal of Experimental Medicine (1967)

This paper describes the relations between the endotoxin concentration and leukocyte pyrogen yield when endotoxin is incubated with whole rabbit blood for 24 hr. The results provide strong evidence for the view that leukocyte pyrogen is not modified endotoxin, and also show that the simplified assay method described in the previous paper works reasonably well.
Computer aided prescribing: Decision support needs to be evidence based
Authors: Siaw-Teng Liaw, Stephen Kerr
Journal: BMJ (2004)

How electronic communication is changing health care Usability is main barrier to effective electronic information systemsEditor-Jadad and Delamothe celebrate "the return of the human" to health informatics in their editorial asking what's next for electronic communication and health care. 1 The question is not whether we need to merge human centred and technology centred approaches: the question is how to do it.If electronic resources are to improve health they have to be accessible, reliable, and usable.More than 80% of websites are currently not accessible by all, including most primary care trust and healthcare charity sites. 2 And according to our unpublished in-house survey, few electronic resources are subject to the rigour we would expect of reliable, evidence based publications, and many of the high quality resources that exist are prohibitively difficult to use in everyday practice.Usability concerns whether an information system is structured so that users can get an answer to fit their purpose.The solution to this problem is user centred design. 3So why isn't it happening in health care?In spite of considerable evidence that user centred design results in cost savings downstream, and a clear need to assess the usability of information systems, 4 the perception remains that it is too expensive.A good first step is the creation of effective, free tools that help us assess the usability of electronic resources quickly, such as our LIDA tool (www.minervation.com/downloads.html).These are needed to show where the problems are in resources that already exist.Once the usability problem has been identified and defined and both users and commissioners have been educated to expect better from information technology systems, momentum will be gathered towards genuinely high quality electronic information systems.
Early Microvascular Recruitment Modulates Subsequent Insulin-Mediated Skeletal Muscle Glucose Metabolism During Lipid Infusion
Authors: Emma M. Eggleston, Linda A. Jahn, Eugene J. Barrett
Journal: Diabetes Care (2012)

To test whether early, insulin-mediated microvascular recruitment in skeletal muscle predicts steady-state glucose metabolism in the setting of physiological elevation of free fatty acid concentrations.We measured insulin's microvascular and metabolic effects in 14 healthy young adults during a 2-h euglycemic insulin clamp. Plasma free fatty acid concentrations were raised (Intralipid and heparin infusion) for 3 h before the clamp and maintained at postprandial concentrations during the clamp. Microvascular blood volume (MBV) was measured by contrast-enhanced ultrasound (CEU) continuously from baseline through the first 30 min of the insulin clamp. Muscle glucose and insulin uptake were measured by the forearm balance method.The glucose infusion rate (GIR) necessary to maintain euglycemia during the clamp varied by fivefold across subjects (2.5-12.5 mg/min/kg). The early MBV responses to insulin, as indicated by CEU video intensity, ranged widely, from a 39% decline to a 69% increase. During the clamp, steady state forearm muscle glucose uptake and GIR each correlated significantly with the change in forearm MBV (P < 0.01). To explore the basis for the wide range of vascular and metabolic insulin sensitivity observed, we also measured V(O(2max)) in a subset of eight subjects. Fitness (V(O(2max))) correlated significantly with the GIR, the forearm glucose uptake, and the percentage change in MBV during the insulin clamp (P < 0.05 for each).Early microvascular responses to insulin strongly associate with steady state skeletal muscle insulin-mediated glucose uptake. Physical fitness predicts both metabolic and vascular insulin responsiveness.
Safety and Survival With GVAX Pancreas Prime and <i>Listeria Monocytogenes</i>–Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer
Authors: Dung T. Le, Andrea Wang-Gillam, Vincent Picozzi, Tim F. Greten, Todd Crocenzi, Gregory Springett, Michael Morse, Herbert Zeh, Deirdre Cohen, Robert L. Fine, Beth Onners, Jennifer N. Uram, Daniel A. Laheru, Eric R. Lutz, Sara Solt, Aimee Luck Murphy, Justin Skoble, Ed Lemmens, John Grous, Thomas Dubensky, Dirk G. Brockstedt, Elizabeth M. Jaffee
Journal: Journal of Clinical Oncology (2015)

Purpose GVAX pancreas, granulocyte-macrophage colony-stimulating factor–secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. GVAX is administered with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. CRS-207, live-attenuated Listeria monocytogenes–expressing mesothelin, induces innate and adaptive immunity. On the basis of preclinical synergy, we tested prime/boost vaccination with GVAX and CRS-207 in pancreatic adenocarcinoma. Patients and Methods Previously treated patients with metastatic pancreatic adenocarcinoma were randomly assigned at a ratio of 2:1 to two doses of Cy/GVAX followed by four doses of CRS-207 (arm A) or six doses of Cy/GVAX (arm B) every 3 weeks. Stable patients were offered additional courses. The primary end point was overall survival (OS) between arms. Secondary end points were safety and clinical response. Results A total of 90 patients were treated (arm A, n = 61; arm B, n = 29); 97% had received prior chemotherapy; 51% had received ≥ two regimens for metastatic disease. Mean number of doses (± standard deviation) administered in arms A and B were 5.5 ± 4.5 and 3.7 ± 2.2, respectively. The most frequent grade 3 to 4 related toxicities were transient fevers, lymphopenia, elevated liver enzymes, and fatigue. OS was 6.1 months in arm A versus 3.9 months in arm B (hazard ratio [HR], 0.59; P = .02). In a prespecified per-protocol analysis of patients who received at least three doses (two doses of Cy/GVAX plus one of CRS-207 or three of Cy/GVAX), OS was 9.7 versus 4.6 months (arm A v B; HR, 0.53; P = .02). Enhanced mesothelin-specific CD8 T-cell responses were associated with longer OS, regardless of treatment arm. Conclusion Heterologous prime/boost with Cy/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with minimal toxicity.
Enhancing the anti-angiogenic action of histone deacetylase inhibitors
Authors: Selena Kuljaca, Tao Liu, Andrew EL Tee, Michelle Haber, Murray D Norris, Tanya Dwarte, Glenn M Marshall
Journal: Molecular Cancer (2007)

Abstract Background Histone deacetylase inhibitors (HDACIs) have many effects on cancer cells, such as growth inhibition, induction of cell death, differentiation, and anti-angiogenesis, all with a wide therapeutic index. However, clinical trials demonstrate that HDACIs are more likely to be effective when used in combination with other anticancer agents. Moreover, the molecular basis for the anti-cancer action of HDACIs is still unknown. In this study, we compared different combinations of HDACIs and anti-cancer agents with anti-angiogenic effects, and analysed their mechanism of action. Results Trichostatin A (TSA) and α-interferon (IFNα) were the most effective combination across a range of different cancer cell lines, while normal non-malignant cells did not respond in the same manner to the combination therapy. There was a close correlation between absence of basal p21 WAF1 expression and response to TSA and IFNα treatment. Moreover, inhibition of p21 WAF1 expression in a p21 WAF1 -expressing breast cancer cell line by a specific siRNA increased the cytotoxic effects of TSA and IFNα. In vitro assays of endothelial cell function showed that TSA and IFNα decreased endothelial cell migration, invasion, and capillary tubule formation, without affecting endothelial cell viability. TSA and IFNα co-operatively inhibited gene expression of some pro-angiogenic factors: vascular endothelial growth factor, hypoxia-inducible factor 1α and matrix metalloproteinase 9, in neuroblastoma cells under hypoxic conditions. Combination TSA and IFNα therapy markedly reduced tumour angiogenesis in neuroblastoma-bearing transgenic mice. Conclusion Our results indicate that combination TSA and IFNα therapy has potent co-operative cytotoxic and anti-angiogenic activity. High basal p21 WAF1 expression appears to be acting as a resistance factor to the combination therapy.
Inactivation of the <i>Lamin A/C</i> Gene by CpG Island Promoter Hypermethylation in Hematologic Malignancies, and Its Association With Poor Survival in Nodal Diffuse Large B-Cell Lymphoma
Authors: Ruben Agrelo, Fernando Setien, Jesus Espada, Maria Jesus Artiga, Maria Rodriguez, Alberto Pérez-Rosado, Abel Sanchez-Aguilera, Mario F. Fraga, Miguel Angel Piris, Manel Esteller
Journal: Journal of Clinical Oncology (2005)

Purpose Lamins support the nuclear envelope and provide anchorage sites for chromatin, but they are also involved in DNA synthesis, transcription, and apoptosis. Although the lack of expression of A-type lamins in lymphoma and leukemia has been reported, the mechanism was unknown. We investigated the possible role of CpG island hypermethylation in lamin A/C silencing and its prognostic relevance. Patients and Methods The promoter CpG island methylation status of the lamin A/C gene, encoding the A-type lamins, was analyzed by bisulfite genomic sequencing and methylation-specific polymerase chain reaction in human cancer cell lines (n = 74; from 17 tumor types), and primary leukemias (n = 60) and lymphomas (n = 80). Lamin A/C expression was determined by reverse-transcription polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence. Results Lamin A/C promoter CpG island methylation was found in hematologic malignancies: seven (50%) of 14 leukemia- and five (42%) of 13 lymphoma cell lines. The presence of hypermethylation was associated with the loss of gene expression while a demethylating agent restored expression. In primary malignancies, lamin A/C hypermethylation was present in 18% (nine of 50) of acute lymphoblastic leukemias and 34% (14 of 41) of nodal diffuse large B-cell lymphomas. The presence of lamin A/C hypermethylation in nodal diffuse large B-cell lymphomas correlated strongly with a decrease in failure-free survival (Kaplan-Meier, P = .0001) and overall survival (Kaplan-Meier, P = .0005). Conclusion Epigenetic silencing of the lamin A/C gene by CpG island promoter hypermethylation is responsible for the loss of expression of A-type lamins in leukemias and lymphomas. The finding that lamin A/C hypermethylation is associated with poor outcome in diffuse large B-cell lymphomas suggests important clinical implications.
Atlas of Clinical Hepatology
Authors: L S Friedman
Journal: Hepatology (1996)

HEPATOLOGY welcomes books for review and invites two chapters review controversial and experimental applications such as tumor analysis and ultrasound its readers both to identify books of hepatological interest and to serve as book reviewers.Books of note should contrast.An appealing feature is a 10-page glossary of Doppler terms at the end of the text.be called to the attention of the Book Editor, and potential reviewers should indicate their areas of interest.Overall, the writing style is direct and understandable.There is a nice balance between text and figures.The Book Editor nonetheless reserves the right to select appropriate reviews for publication on these pages.The color plates are state-of-the-art, superb, and numerous.The Doppler findings are well integrated with real time sonographic images, figures, and correlative studies.Although the references are adequate, the Clinical Application of Doppler Ultrasound.Ed most recent are scattered listings from 1993.Unfortu-2.Edited by Kenneth J. W. Taylor, Peter N. Burns, nately, this can result in important omissions in the and Peter N
Pemphigus vegetans in a child
Authors: J.H. SILLEVIS SMITT, T.J. MULDER, F.W. ALBEDA, J.C. NIEROP
Journal: British Journal of Dermatology (1992)

Pemphigus vegetans was diagnosed in a 12-year-old boy based on clinical, histopathological and immunohistological findings. To our knowledge, this is the first case of juvenile pemphigus vegetans to be published in the literature. Suggested treatment with prednisone and azathioprine was refused, and the patient was treated with a decoction of herbs prescribed by a practitioner of traditional Chinese herbal medicine. This treatment gave excellent results. Possible active components of the treatment are discussed.
Reply to J.R. Carver et al
Authors: Grzegorz S. Nowakowski, Thomas E. Witzig, Matthew J. Maurer, James R. Cerhan
Journal: Journal of Clinical Oncology (2010)

The letter by Carver et al, to our knowledge, represents the fourth independent study documenting no change in response rates based on statin use in rituximab-treated patients with B-cell nonHodgkin’s lymphoma. In this regard, it provides an additional validation of previous studies indicating that concurrent statin use does not affect the clinical efficacy of rituximab and rituximabcontaining therapy. Although the apparent discordance between in vitro studies and the lack of clinical impact on patient outcome requires additional laboratory studies, it also illustrates that the potential for a loss in translation between the laboratory and clinic is a problem in making clinical decisions on the basis of in vitro studies alone.
Intrathecal Ziconotide in the Treatment of Refractory Pain in Patients With Cancer or AIDS
Authors: Peter S Staats, Thomas Yearwood, Steven G Charapata, Robert W Presley, Mark S Wallace, Michael Byas-Smith, Robert Fisher, David A Bryce, Eugene A Mangieri, Robert R Luther, Martha Mayo, Dawn McGuire, David Ellis
Journal: JAMA (2004)

Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive calcium channels and may be effective in patients with pain that is refractory to opioid therapy or those with intolerable opioid-related adverse effects.To assess the safety and efficacy of intrathecal ziconotide in patients with pain that is refractory to conventional treatment.Double-blind, placebo-controlled, randomized trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia, and the Netherlands. Patients were 111 individuals ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive ziconotide or placebo treatment.Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group.Mean percentage change in VASPI score from baseline to the end of the initial titration period.Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline (median morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for the placebo group; P =.63, based on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group (P =.18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase. Pain relief was moderate to complete in 52.9% of patients in the ziconotide group compared with 17.5% in the placebo group (P<.001). Five patients receiving ziconotide achieved complete pain relief, and 50.0% of patients receiving ziconotide responded to therapy compared with 17.5% of those receiving placebo (P =.001).Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS.
Malignant mesothelioma of the pleura in Barrow-in-Furness.
Authors: J R Edge, S L Choudhury
Journal: Thorax (1978)

Ffty cases of malignant pleural mesothelioma (47 men and 3 women) have been diagnosed during the period 1966-76 in Barrow-in-Furness, all of them histologically proved and accepted by the Pneumoconiosis Panel. At the time of writing only three survive. There was a history of industrial exposure to asbestos in all 47 men, who had worked in various trades in the shipyard, as had one of the women. One of the women was married to a shipyard plumber, who may have brought home asbestos dust on his clothes. Only one patient, a housewife, aged 28 at diagnosis, had no known asbestos contact. The asbestos content of the lungs has been measured in the last 20 cases, in 18 of whom it was found to be substantially greater than the accepted levels for the general population. In a small number studied by electron microscopy, the predominant fibre was crocidolite. A positive histological diagnosis was achieved in 39 subjects during life in the expectation of securing industrial compensation, but, in spite of this, less than half of the dependants are currently receiving payments. Metastases, though never clinically apparent, were frequent at necropsy.