tbuckley/cabot-search huggingface dataset:
THE PHOTOSENSITIVITY DERMATITIS AND ACTINIC RETICULOID SYNDROME (PD/AR) IN FOUR YOUNG PATIENTS WITH ATOPIC ECZEMA
Authors: SC Russell, Dawe RS, Collins P
Journal: British Journal of Dermatology (1995)

Journal Article THE PHOTOSENSITIVITY DERMATITIS AND ACTINIC RETICULOID SYNDROME (PD/AR) IN FOUR YOUNG PATIENTS WITH ATOPIC ECZEMA Get access SC Russell, SC Russell Ferguson J. Photobiology Unit, Department of Dermatology, Ninewells Hospital, Dundee Search for other works by this author on: Oxford Academic Google Scholar Dawe RS, Dawe RS Ferguson J. Photobiology Unit, Department of Dermatology, Ninewells Hospital, Dundee Search for other works by this author on: Oxford Academic Google Scholar Collins P Collins P Department of Dermatology, Leeds General Infirmary, Leeds. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue s45, 1 July 1995, Pages 62–63, https://doi.org/10.1111/j.1365-2133.1995.tb15402.x Published: 01 July 1995
NF-kappa B and I kappa B alpha: an inducible regulatory system in endothelial activation.
Authors: M A Read, M Z Whitley, A J Williams, T Collins
Journal: The Journal of Experimental Medicine (1994)

Structural analysis of the promoters of several endothelial genes induced at sites of inflammatory or immune responses reveals binding sites for the transcription factor nuclear factor kappa B (NF-kappa B). Endothelial cells express transcripts encoding the p50/p105 and p65 components of NF-kappa B and the rel-related proto-oncogene c-rel; steady state levels of these transcripts are transiently increased by tumor necrosis factor alpha (TNF-alpha). Western blotting revealed that stimulation of endothelial cells with TNF-alpha resulted in nuclear accumulation of the p50 and p65 components of NF-kappa B. Ultraviolet crosslinking and immunoprecipitation demonstrated binding of the p50 and p65 components of NF-kappa B to the E-selectin kappa B site. Endothelial cells express an inhibitor of NF-kappa B activation, I kappa B-alpha (MAD-3). Protein levels of this inhibitor fall rapidly after TNF-alpha stimulation. In parallel, p50 and p65 accumulate in the nucleus and RNA transcript levels for I kappa B-alpha are dramatically upregulated. Recombinant p65 stimulates expression of E-selectin promoter-reporter constructs. I kappa B-alpha inhibits p65 or TNF-alpha-stimulated E-selectin promoter-reporter gene expression in transfected endothelial cells. The NF-kappa B and I kappa B-alpha system may be an inducible regulatory mechanism in endothelial activation.
Novel concepts in airway inflammation and remodelling in asthma
Authors: Sejal Saglani, Clare M. Lloyd
Journal: European Respiratory Journal (2015)

The hallmark pathological features of asthma include airway eosinophilic inflammation and structural changes (remodelling) which are associated with an irreversible loss in lung function that tracks from childhood to adulthood. In parallel with changes in function, pathological abnormalities occur early, during the pre-school years, are established by school age and subsequently remain (even though symptoms may remit for periods during adulthood). Given the equal importance of inflammation and remodelling in asthma pathogenesis, there is a significant disparity in studies undertaken to investigate the contribution of each. The majority focus on the role of inflammation, and although novel therapeutics such as those targeted against T-helper cell type 2 (Th2) mediators have arisen, it is apparent that targeting inflammation alone has not allowed disease modification. Therefore, unless airway remodelling is addressed for future therapeutic strategies, it is unlikely that we will progress towards a cure for asthma. Having acknowledged these limitations, the focus of this review is to highlight the gaps in our current knowledge about the mechanisms underlying airway remodelling, the relationships between remodelling, inflammation and function, remodelling and clinical phenotypes, and the importance of utilising innovative and realistic pre-clinical models to uncover effective, disease-modifying therapeutic strategies.
Small RNAs Are Raising Big Expectations
Authors: Karyn Hede
Journal: JNCI Journal of the National Cancer Institute (2009)

Five years ago there were little more than 200 known microRNAs (miRNAs) — small regulatory nucleic acids that bind to complementary sites on mRNAs and prevent their translation into protein. Today, that number has swelled to more than 700 and counting. The explosion in knowledge about these small, noncoding RNAs, which appear to be evolutionarily ancient but were discovered less than two decades ago, has already led to the marketing of new cancer diagnostic tools and, researchers say, may eventually lead to treatments. Take the case of “cancers of unknown primary” (CUPs) — cancers that clearly originated in another, unknown site.
Local Control, Survival, and the Fisher Hypothesis
Authors: Richard G. Margolese
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: Rabinovitch and Kavanagh seek a middle ground between the Fisher and Halsted concepts of breast cancer. They report that a meta-analysis showed a highly significant reduction in annual breast cancer mortality when patients who had undergone lumpectomy also received radiation therapy. Yet the single largest trial evaluating these treatments reported no difference in overall survival (OS) out to 20 years. Should meta-analyses always trump prospective trials? In fact, the B-06 trial can be interpreted as a confirmation of the B-04 trial. Both trials illustrate the lack of effect on OS when local control is clearly not obtained. In the case of B-04, 39% of the patients with clinically negative axillae randomly assigned to radical mastectomy had histologically positive nodes. Those randomly assigned to no axillary treatment obviously had the same incidence of histologic disease, yet only 18% ever developed clinical evidence of recurrence in the axilla. Although that subset had an inferior survival, the overall group of patients with untreated axillae had the same OS as those having the Halsted radical mastectomy. Similarly, after lumpectomy, radiation therapy reduced the local recurrence rate from 38% to 9%. Although the subsets with local recurrence did worse, the overall outcome of the total mastectomy group or the radiation therapy group was not better than the lumpectomy alone group. One fairly obvious conclusion is that pathologic margin sampling does not find all positive margins and it is the radiation therapy that helps boost local control, but this does not translate to better OS. In both trials, the group suffering locoregional recurrence does worse, but there is a danger of confusing cause and effect and interpreting this to mean that local control improves OS. The better interpretation is that some local recurrences are really a manifestation of systemic disease, and these cause the subgroup to have inferior survival. This would explain why in these trials improved local control did not improve OS. This leaves these trial results at odds with the meta analysis, but these two large randomized prospective clinical trials tested the same hypothesis in two different clinical arenas—B04 was a trial of lymph node control, B-06 was a trial of breast parenchyma. Both have provided confirmation of the Fisher hypothesis with 20and 25year follow-up.
Urinary tract infection in children.
Authors: A M Dighe
Journal: BMJ (1984)

three": the rule states that if none of n patients shows the event about which we are concerned, we can be 95%0 confident that the chance of this event occurring is at most three in n-that is, 3/n.In other words the upper 95%°, confidence limit of a 0/n rate is 3/n.Combining our observations with those of Dr Hosie and Dr Hosie the risk of hydralazine induced lupus when the daily dose is limited to 100 mg in men and 50 mg in women is likely to be at most 3/176-1 7,O,.This figure suggests to us that these dose limits for hydralazine are acceptably safe.As we stated in our original article, however, the antihypertensive effect of such low dose hydralazine will often prove unsatisfactory.
Antenatal infection in the rabbit impairs post-natal growth and lung alveolarisation
Authors: C. Gras-Le Guen, C. Denis, M-L. Franco-Montoya, A. Jarry, C. Delacourt, G. Potel, J. Bourbon, J-C. Roze, P-H. Jarreau
Journal: European Respiratory Journal (2008)

Clinical and experimental studies indicate an association between chorioamnionitis and bronchopulmonary dysplasia in preterm infants. The present authors hypothesised that, in the rabbit, antenatal infection may impair lung development after birth, despite effective maternal antibiotic therapy. Pregnant rabbits received an intra-uterine inoculation of 10(3) Escherichia coli colony forming units or vehicle at the end of gestation (day 29). Intravenous ceftriaxone therapy was initiated 8 h after inoculation for a period of 8 days. Pups born between 60 and 84 h after inoculation were kept with their mother until sacrifice on days 0, 1, 5, 8 and 15. Blood cultures from antenatally infected animals were sterile at birth. Postnatal growth was significantly impaired by day 8. Lung morphometry showed a significant decrease of alveolar surface density and interstitial density, with a significant increase of alveolar airspace volume, indicating impaired alveolarisation for the first 2 weeks of postnatal life. Inflammatory and apoptotic processes were not detected in the lung at birth or subsequently. Intra-uterine infection in rabbits is, therefore, responsible for concomitant postnatal growth retardation and abnormal pulmonary development despite early and effective antenatal antibiotic therapy. This may constitute an alternative model to study the consequences of antenatal infection on postnatal growth and lung development.
ADAMTS-7 Mediates Vascular Smooth Muscle Cell Migration and Neointima Formation in Balloon-Injured Rat Arteries
Authors: Li Wang, Jingang Zheng, Xue Bai, Bo Liu, Chuan-ju Liu, Qingbo Xu, Yi Zhu, Nanping Wang, Wei Kong, Xian Wang
Journal: Circulation Research (2009)

The migration of vascular smooth muscle cells (VSMCs) plays an essential role during the development of atherosclerosis and restenosis. Extensive studies have implicated the importance of extracellular matrix (ECM)-degrading proteinases in VSMC migration. A recently described family of proteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), is capable of degrading vascular ECM proteins. Here, we sought to determine whether ADAMTS-7 is involved in VSMC migration and neointima formation in response to vascular injury. ADAMTS-7 protein accumulated preferentially in neointima of the carotid artery wall after balloon injury. In primary VSMCs, ADAMTS-7 level was enhanced by the proinflammatory cytokine tumor necrosis factor alpha and growth factor platelet-derived growth factor-BB. ADAMTS-7 overexpression greatly accelerated and small interfering RNA knockdown markedly retarded VSMC migration/invasion in vitro. In addition, luminal delivery of ADAMTS-7 adenovirus to carotid arteries exacerbated intimal thickening nearly sixfold 7 days after injury. Conversely, perivascular administration of ADAMTS-7 small interfering RNA but not scramble small interfering RNA to injured arteries attenuated intimal thickening by 50% at 14 days after injury. Furthermore, ADAMTS-7 mediated degradation of the vascular ECM cartilage oligomeric matrix protein (COMP) in injured vessels. Replenishing COMP circumvented the promigratory effect of ADAMTS-7 on VSMCs. Enforced expression of COMP significantly suppressed VSMC migration and neointima formation postinjury, which indicates that ADAMTS-7 facilitated intimal hyperplasia through degradation of inhibitory matrix protein COMP. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and postangioplasty restenosis.
New England Journal's publisher in conflict of interest dispute
Authors: S. Gottlieb
Journal: BMJ (1999)

A prominent official of the Massachusetts Medical Society, the non-profit group that owns the New England Journal of Medicine, has been criticised for not adequately disclosing his financial ties to an internet start-up company that has concluded a lucrative deal with his journal.

Some officials of the Massachusetts Medical Society and the New England Journal of Medicine say …
LNA-mediated anti–miR-155 silencing in low-grade B-cell lymphomas
Authors: Yong Zhang, Aldo M. Roccaro, Christopher Rombaoa, Ludmilla Flores, Susanna Obad, Stacey M. Fernandes, Antonio Sacco, Yang Liu, Hai Ngo, Phong Quang, Abdel Kareem Azab, Feda Azab, Patricia Maiso, Michaela Reagan, Jennifer R. Brown, To-Ha Thai, Sakari Kauppinen, Irene M. Ghobrial
Journal: Blood (2012)
Inhibition of adrenergic neurotransmission in canine vascular smooth muscle by histamine: mediation by H2-receptors.
Authors: M A McGrath, J T Shepherd
Journal: Circulation Research (1976)

Histamine depressed the contractions of dog saphenous vein strips caused by stimulation of their sympathetic nerves. This was due to a decrease in the release of norepinephrine which appears to be mediated by histamine H2-receptors. The evidence for this is as follows: (1) Contractions of the strips caused by activating the nerve endings electrically or by depolarization with potassium ions were depressed by histamine, whereas contractions caused by tyramine and norepinephrine were either unchanged or augmented. (2) Strips were incubated with norepinephrine[7-3H] and mounted for superfusion and isometric tension recording. The perfusate was collected for estimation of total radioactivity and for column chromatographic separation of norpinephrine and its metabolites. Histamine (0.9 muM) depressed the release of norepinphrine[7-3H] during contractions caused by electric stimulation, whereas the release of radioactive compounds caused by tyramine was unaffected. (3) The depression by histamine of the contractions and the efflux of radioactive compounds caused by electric stimulation were inhibited by an H2-receptor antagonist (metiamide), but were unaffected by an H1-receptor antagonist (pyrilamine). (4) Contractions caused by electric stimulation were inhibited by an H2-receptor agonist (4-methylhistamine) and augmented by an H1-receptor agonist (2-methylhistamine). These findings suggest the possibility that histamine, which is abundant in sympathetic nerves, might have a regulatory role in the release of the neurotransmitter.
Physical activity and liver diseases
Authors: Annalisa Berzigotti, Uttara Saran, Jean‐François Dufour
Journal: Hepatology (2015)

Regular physical activity beneficially impacts the risk of onset and progression of several chronic diseases. However, research regarding the effects of exercising on chronic liver diseases is relatively recent. Most researchers focused on nonalcoholic fatty liver disease (NAFLD), in which increasing clinical and experimental data indicate that skeletal muscle crosstalking to the adipose tissue and the liver regulates intrahepatic fat storage. In this setting, physical activity is considered to be required in combination with calories restriction to allow an effective decrease of intrahepatic lipid component, and despite that evidence is not conclusive, some studies suggest that vigorous activity might be more beneficial than moderate activity to improve NAFLD/nonalcoholic steatohepatitis. Evidence regarding the effects of exercise on the risk of hepatocellular carcinoma is scarce; some epidemiological studies indicate a lower risk in patients regularly and vigorously exercising. In compensated cirrhosis, exercise acutely increases portal pressure, but in the longer term it has been proved safe and probably beneficial. Decreased aerobic capacity (VO2 ) correlates with mortality in patients with decompensated cirrhosis, who are almost invariably sarcopenic. In these patients, VO2 is improved by physical activity, which might also reduce the risk of hepatic encephalopathy through an increase in skeletal muscle mass. In solid organ transplantation recipients, exercise is able to improve lean mass, muscle strength, and, as a consequence, aerobic capacity. Few data exist in liver transplant recipients, in whom exercise should be an object of future studies given its high potential of providing long-term beneficial effects.Despite that evidence is far from complete, physical activity should be seen as an important part of the management of patients with liver disease in order to improve their clinical outcome.
Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Neutropenia during Phase I Development of Liposome-Entrapped Paclitaxel
Authors: Gerald J. Fetterly, Thaddeus H. Grasela, Jeffrey W. Sherman, Jeanne L. Dul, Amy Grahn, Diane Lecomte, Jill Fiedler-Kelly, Nevena Damjanov, Mayer Fishman, Michael P. Kane, Eric H. Rubin, Antoinette R. Tan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of liposome-entrapped paclitaxel easy-to-use (LEP-ETU) and to characterize the relationship between LEP-ETU concentrations and the time course of neutropenia in cancer patients. Experimental Design: LEP-ETU was administered to 88 patients and 63 were evaluable for pharmacokinetic/pharmacodynamic (PK/PD) analysis following 1.5- and 3-h infusions every 3 weeks (q3w; dose range, 135-375 mg/m2). MTD was identified using a 3 + 3, up-and-down dose-finding algorithm. PK/PD modeling was done to describe the temporal relationship between paclitaxel concentrations and neutrophil count. Simulations assessed the influence of dose and schedule on neutropenia severity to help guide dose selection. Results: The MTD of LEP-ETU was identified as 325 mg/m2. DLTs occurring at 375 mg/m2 consisted of febrile neutropenia and neuropathy. The Cmax and area under the plasma concentration-time curve of LEP-ETU were less than proportional with increasing dose. The PK/PD model showed that LEP-ETU inhibition of neutrophil proliferation was 9.1% per 10 μg/mL of total paclitaxel concentration. The incidence of grade 4 neutropenia increased from 33% to 42% across the dose range of 275 to 325 mg/m2 q3w. For a dose of 110 mg/m2 given weekly, grade 4 neutropenia was estimated to be 16% compared with 42% for the same total dose administered q3w. Conclusions: LEP-ETU can be administered safely at higher doses than Taxol. Modeling and simulation studies predict that 325 mg/m2 LEP-ETU q3w provides acceptable neutropenic events relative to those observed at 175 mg/m2 Taxol q3w. A 275 mg/m2 dose may offer an improved therapeutic index.
Favorable Effects of Inhaled Treprostinil in Severe Pulmonary Hypertension
Authors: Robert Voswinckel, Beate Enke, Frank Reichenberger, Markus Kohstall, Andree Kreckel, Stefanie Krick, Henning Gall, Tobias Gessler, Thomas Schmehl, Hossein A. Ghofrani, Ralph Theo Schermuly, Friedrich Grimminger, Lewis J. Rubin, Werner Seeger, Horst Olschewski
Journal: Journal of the American College of Cardiology (2006)
Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus
Authors: Varun Garg, Rolf van Heeswijk, Jee Eun Lee, Katia Alves, Priya Nadkarni, Xia Luo
Journal: Hepatology (2011)

Abstract: The hepatitis C virus protease inhibitor telaprevir is an inhibitor of the enzyme cytochrome P450 3A, responsible for the metabolism of both cyclosporine and tacrolimus. This Phase I, open-label, nonrandomized, single-sequence study assessed the effect of telaprevir coadministration on the pharmacokinetics of a single dose of either cyclosporine or tacrolimus in two separate panels of 10 healthy volunteers each. In Part A, cyclosporine was administered alone as a single 100-mg oral dose, followed by a minimum 8-day washout period, and subsequent coadministration of a single 10-mg oral dose of cyclosporine with either a single dose of telaprevir (750 mg) or with steady-state telaprevir (750 mg every 8 hours [q8h]). In Part B, tacrolimus was administered alone as a single 2-mg oral dose, followed by a minimum 14-day washout period, and subsequent coadministration of a single 0.5-mg dose of tacrolimus with steady-state telaprevir (750 mg q8h). Coadministration with steady-state telaprevir increased cyclosporine dose-normalized (DN) exposure (DN_AUC 0-∞ ) by approximately 4.6-fold and increased tacrolimus DN_AUC 0-∞ by approximately 70-fold. Coadministration with telaprevir increased the terminal elimination half-life (t ½ ) of cyclosporine from a mean (standard deviation [SD]) of 12 (1.67) hours to 42.1 (11.3) hours and t ½ of tacrolimus from a mean (SD) of 40.7 (5.85) hours to 196 (159) hours. Conclusion : In this study, telaprevir increased the blood concentrations of both cyclosporine and tacrolimus significantly, which could lead to serious or life-threatening adverse events. Telaprevir has not been studied in organ transplant patients; its use in these patients is not recommended because the required studies have not been completed to understand appropriate dose adjustments needed for safe coadministration of telaprevir with cyclosporine or tacrolimus, and regulatory approval has not been obtained. (HEPATOLOGY 2011;)
Rating Health Information on the Internet
Authors: A R Jadad, A Gagliardi
Journal: JAMA (1998)

Context.—The rapid growth of the Internet has triggered an information revolution of unprecedented magnitude. Despite its obvious benefits, the increase in the availability of information could also result in many potentially harmful effects on both consumers and health professionals who do not use it appropriately.Objectives.—To identify instruments used to rate Web sites providing health information on the Internet, rate criteria used by them, establish the degree of validation of the instruments, and provide future directions for research in this area.Data Sources.—MEDLINE (1966-1997), CINHAL (1982-1997), HEALTH (1975-1997), Information Science Abstracts (1966 to September 1995), Library and Information Science Abstracts (1969-1995), and Library Literature (1984-1996); the search engines Lycos, Excite, Open Text, Yahoo, HotBot, Infoseek, and Magellan; Internet discussion lists; meeting proceedings; multiple Web pages; and reference lists.Instrument Selection.—Instruments used at least once to rate the quality of Web sites providing health information with their rating criteria available on the Internet.Data Extraction.—The name of the developing organization, Internet address, rating criteria, information on the development of the instrument, number and background of people generating the assessments, and data on the validity and reliability of the measurements.Data Synthesis.—A total of 47 rating instruments were identified. Fourteen provided a description of the criteria used to produce the ratings, and 5 of these provided instructions for their use. None of the instruments identified provided information on the interobserver reliability and construct validity of the measurements.Conclusions.—Many incompletely developed instruments to evaluate health information exist on the Internet. It is unclear, however, whether they should exist in the first place, whether they measure what they claim to measure, or whether they lead to more good than harm.