tbuckley/cabot-search huggingface dataset:
A multicentre, single-blind, randomized comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac<sup>®</sup>) applied once daily and a clindamycin lotion formulation (Dalacin T<sup>®</sup>) applied twice daily in the topical treatment of acne vulgaris
Authors: CH.C. Zouboulis, L. Derumeaux, J. Decroix, B. Maciejewska-Udziela, F. Cambazard, A. Stuhlert
Journal: British Journal of Dermatology (2000)

A successful phase III pilot study compared the efficacy and safety of a fixed clindamycin 1%/tretinoin 0.025% gel formulation (CTG; Velac gel) applied once daily and a clindamycin 1% lotion formulation (CLN; Dalacin T lotion) applied twice daily in the treatment of moderate to severe acne vulgaris.We aimed to follow up this study.The two treatment regimens were compared in a multicentre, single-blind, randomized 12-week investigation of patients with moderate to severe acne vulgaris.At week 12, the mean percentage reduction in non-inflamed lesions (open and closed comedones) was greater in the CTG group compared with the CLN group (P = 0.05). Absolute reductions in open and closed comedones were also greater in the CTG group, consistent with the comedolytic activity of tretinoin. There was a significantly greater absolute reduction in inflamed lesions (pustules, papules and nodules) from baseline to both end-point (last observed efficacy outcome; P = 0.043) and week 12 (P = 0.018) in the CTG group compared with the CLN group. Evaluation of the calculated overall acne severity score, considering all five lesion subtypes, demonstrated a significantly greater mean percentage reduction in the CTG group compared with the CLN group, both at end-point (P = 0.01) and at week 12 (P < 0.01). The more subjective assessment of overall acne severity according to the Cook scale also demonstrated a significantly greater mean reduction in the CTG group than the CLN group after 12 weeks of therapy (P = 0.007). CTG had a more rapid effect on the onset of improvement compared with CLN; a 50% reduction in total lesion counts by day 60 was found in 77% of patients on CTG compared with 56% receiving CLN (P = 0.003). This was largely due to the reduction in open comedone counts (P = 0. 0006). For all other variables, CTG was at least as effective as CLN. Both treatments were well tolerated.A single daily topical application of Velac gel was superior to Dalacin T lotion applied twice daily in reducing overall acne scores, and was faster acting. The simpler dosing regimen of Velac gel and its rapid effect are likely to have a positive effect on both patient compliance and cost.
Prophylaxis against postoperative pulmonary embolism.
Authors: A M Smith
Journal: BMJ (1980)

problems, and deafness,9 10 as well as sudden infant death."112The task of clearing the population of potentially dangerous viruses before immuni- sation may well prove impossible; but does that justify our setting up ill-founded contra- indications, rather than real ones, and then shooting them down in order to prove that our vaccines are safe ?
Change in End-of-Life Care for Medicare Beneficiaries
Authors: Joan M. Teno, Pedro L. Gozalo, Julie P. W. Bynum, Natalie E. Leland, Susan C. Miller, Nancy E. Morden, Thomas Scupp, David C. Goodman, Vincent Mor
Journal: JAMA (2013)

A recent Centers for Disease Control and Prevention report found that more persons die at home. This has been cited as evidence that persons dying in the United States are using more supportive care.To describe changes in site of death, place of care, and health care transitions between 2000, 2005, and 2009.Retrospective cohort study of a random 20% sample of fee-for-service Medicare beneficiaries, aged 66 years and older, who died in 2000 (n = 270,202), 2005 (n = 291,819), or 2009 (n = 286,282). A multivariable regression model examined outcomes in 2000 and 2009 after adjustment for sociodemographic characteristics. Based on billing data, patients were classified as having a medical diagnosis of cancer, chronic obstructive pulmonary disease, or dementia in the last 180 days of life.Site of death, place of care, rates of health care transitions, and potentially burdensome transitions (eg, health care transitions in the last 3 days of life).Our random 20% sample included 848,303 fee-for-service Medicare decedents (mean age, 82.3 years; 57.9% female, 88.1% white). Comparing 2000, 2005, and 2009, the proportion of deaths in acute care hospitals decreased from 32.6% (95% CI, 32.4%-32.8%) to 26.9% (95% CI, 26.7%-27.1%) to 24.6% (95% CI, 24.5%-24.8%), respectively. However, intensive care unit (ICU) use in the last month of life increased from 24.3% (95% CI, 24.1%-24.5%) to 26.3% (95% CI, 26.1%-26.5%) to 29.2% (95% CI, 29.0%-29.3%). (Test of trend P value was <.001 for each variable.) Hospice use at the time of death increased from 21.6% (95% CI, 21.4%-21.7%) to 32.3% (95% CI, 32.1%-32.5%) to 42.2% (95% CI, 42.0%-42.4%), with 28.4% (95% CI, 27.9%-28.5%) using a hospice for 3 days or less in 2009. Of these late hospice referrals, 40.3% (95% CI, 39.7%-40.8%) were preceded by hospitalization with an ICU stay. The mean number of health care transitions in the last 90 days of life increased from 2.1 (interquartile range [IQR], 0-3.0) to 2.8 (IQR, 1.0-4.0) to 3.1 per decedent (IQR, 1.0-5.0). The percentage of patients experiencing transitions in the last 3 days of life increased from 10.3% (95% CI, 10.1%-10.4%) to 12.4% (95% CI, 12.3%-2.5%) to 14.2% (95% CI, 14.0%-14.3%).Among Medicare beneficiaries who died in 2009 and 2005 compared with 2000, a lower proportion died in an acute care hospital, although both ICU use and the rate of health care transitions increased in the last month of life.
THU0165 Predictive Value of Different Remission Criteria for a Good Functional Status Outcome: Results from the Espoir Cohort
Authors: I. Castrejón, M. Dougados, B. Combe, F. Guillemin, B. Fautrel, T. Pincus
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Different criteria for remission in rheumatoid arthritis (RA) have been developed from a core data set of 7 measures for the DAS28, CDAI and RAPID3. A committee of the American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR) proposed two criteria: "Boolean" criteria with 4 measures – TJC28, SJC28, CRP, PATGL – all ≤1; and SDAI ≤3.3 [1]. A recent study indicated that remission criteria based on RAPID3 ≤3 with ≤1 swollen joint (RAPID3RJ1) gave similar results to the Boolean and SDAI criteria, but would be considerably more feasible for usual care [2]. <h3>Objectives</h3> To analyze the capacity of 6 remission criteria, based on a health assessment questionnaire (HAQ) in the ESPOIR routine care cohort of early arthritis patients, to predict a good outcome for physical function 12 months later. <h3>Methods</h3> The ESPOIR cohort includes patients with early RA who had baseline DAS28 ≥5.1 and received routine care chosen by their doctor. A good outcome for physical function on the HAQ was defined as no change and absolute score of ≤0.5 at both the 12 and 24 month time points. Remission was defined at 12 months according to 6 criteria: ACR/EULAR Boolean (TJC28, SJC28, CRP, PATGL all ≤1), SDAI (≤3.3), CDAI (≤2.8), DAS28 (≤2.6), RAPID3 (≤3) and RAPID3RJ1 (RAPID3 ≤3 and ≤1 swollen joint). Analyses were conducted to determine whether patients who met different criteria for remission at 12 months were more likely to have a good functional outcome 12 months later (at 24 months), by comparing patients who were classified as in remission or not in remission using a chi square test, and likelihood ratios for each of the 6 remission criteria. <h3>Results</h3> 656 patients had available data to evaluate remission; 76% were women and mean age was 48 years. The median duration of disease at baseline was 5 months; 40% of patients were ACPA-positive and 44% rheumatoid factor-positive. Patients who were in remission according to each of 6 criteria were significantly more likely to have a good functional status outcome 12 months later (Table); nonetheless, 45-50% of patients not in remission also had a good functional outcome 12 months later. Positive likelihood ratios for having a good functional outcome were 3.8 and 4.0 for Boolean and RAPID3RJ1; 2.8-3.1 for RAPID3, CDAI and SDAI; and 1.8 for DAS28 criteria. <h3>Conclusions</h3> Remission according to the 6 criteria predicts a good functional outcome 12 months later. The highest positive likelihood ratios are seen for the Boolean and RAPID3RJ1 criteria. <h3>References</h3> Felson DT, Smolen JS, Wells G, et al. Arthritis Rheum 2011;63:573-586. Castrejón I, Dougados M, Combe B, et al. J Rheumatol 2013; in press <h3>Disclosure of Interest</h3> None Declared
Cytokines from activated T cells induce normal endothelial cells to acquire the phenotypic and functional features of AIDS-Kaposi's sarcoma spindle cells.
Authors: V Fiorelli, R Gendelman, F Samaniego, P D Markham, B Ensoli
Journal: Journal of Clinical Investigation (1995)

Kaposi's sarcoma (KS) is a proliferative disease of vascular origin particularly frequent in HIV-1-infected homosexual men (AIDS-KS) and characterized by proliferating spindle-shaped cells, angiogenesis, and inflammatory cell infiltration. Previous work has suggested that KS spindle cells are of endothelial cell origin and that chronic immune activation via the release of inflammatory cytokines may cooperate with basic fibroblast growth factor (bFGF) and the HIV-1 Tat protein in the induction and progression of AIDS-KS. Here we show that KS spindle cells have features of activated endothelial cells, and that conditioned media from activated T cells, rich in the same inflammatory cytokines increased in HIV-1-infected individuals, induce normal endothelial cells to acquire the phenotypic and functional features of KS cells. These include (a) acquisition of a similar pattern of cell surface antigen expression; (b) similar proliferative response to bFGF; (c) induction of the responsiveness to the mitogenic effect of extracellular HIV-1 Tat protein that is now able to promote the G1-S transition of endothelial cell cycle; and (d) induction in nude mice of vascular lesions closely resembling early KS as well as the lesions induced by inoculation of KS cells. These results suggest that chronic immune activation, via release of inflammatory cytokines, may play a role in the induction of KS.
Photodynamic therapy with topical methyl aminolaevulinate for 'difficult-to-treat' basal cell carcinoma
Authors: C. Vinciullo, T. Elliott, D. Francis, K. Gebauer, L. Spelman, R. Nguyen, W. Weightman, A. Sheridan, C. Reid, D. Czarnecki, D. Murrell
Journal: British Journal of Dermatology (2005)

Background Basal cell carcinoma (BCC) may be difficult to treat by conventional means, particularly if the lesions are large or located in the mid‐face (H‐zone). Photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL) may be a good noninvasive option for these patients. Objectives To investigate the efficacy and safety of PDT using MAL for BCCs defined as 'difficult to treat', i.e. large lesions, in the H‐zone, or in patients at high risk of surgical complications. Methods This was a prospective, multicentre, noncomparative study. Patients were assessed 3, 12 and 24 months after the last PDT treatment. One hundred and two patients with 'difficult‐to‐treat' BCC were treated with MAL PDT, using 160 mg g−1 cream and 75 J cm−2 red light (570–670 nm), after lesion preparation and 3 h of cream exposure. Results Ninety‐five patients with 148 lesions were included in the per protocol analysis. The histologically confirmed lesion complete response rate at 3 months was 89% (131 of 148). At 12 months, 10 lesions had reappeared, and therefore the cumulative treatment failure rate was 18% (27 of 148). At 24 months, an additional nine lesions had reappeared, resulting in a cumulative treatment failure rate of 24% (36 of 148). The estimated sustained lesion complete response rate (assessed using a time‐to‐event approach) was 90% at 3 months, 84% at 12 months and 78% at 24 months. Overall cosmetic outcome was judged as excellent or good in 79% and 84% of the patients at 12 and 24 months, respectively. Follow‐up is continuing for up to 5 years. Conclusions MAL PDT is an attractive option for 'difficult‐to‐treat' BCC. Because of the excellent cosmetic results, the treatment is particularly well suited for lesions that would otherwise require extensive surgical procedures.
THE ACTION OF EXTREME COLD ON LEUKEMIC CELLS OF MICE
Authors: Charles Breedis
Journal: The Journal of Experimental Medicine (1942)

Suspensions of leukemic cells of mice from three different strains of leukemia were subjected to rapid or slow freezing and rapid or slow thawing. Suspensions rapidly frozen to -196 degrees C. were in all cases innocuous, whereas those frozen slowly were capable of transmitting leukemia. The infectivity of slowly frozen material varied from an estimated 0.0001 per cent to 1 per cent of that of fresh material, and this figure probably represents the percentage of surviving leukemic cells. Particles of spleen and lymph node reacted to slow and rapid freezing in the same manner as suspensions prepared from them. For one of the strains rapid thawing was less injurious than slow thawing; for the other two the rate of thawing seemed to be immaterial. Infectivity was equally well preserved after freezing to -21 degrees C. whether freezing occurred spontaneously after supercooling or was initiated near the freezing point by inoculation with ice, or whether thawing was slow or rapid. Suspensions already slowly frozen at temperatures of -2 degrees or lower, whether spontaneously or by inoculation with ice, could no longer be completely inactivated by subsequent rapid cooling to -196 degrees C. Unfrozen suspensions initially above the freezing point or supercooled to -2 degrees C. or -8 degrees C. and then rapidly cooled to -196 degrees C. were inactivated. This protective action of previous slow freezing was most marked when the initial temperature of the frozen suspension was -15 degrees C. or lower; when it was -2 degrees C. protection was barely detected. These observations indicate that the changes which are peculiar to rapid freezing alone and lead to complete inactivation take place during rapid transition from the liquid to the solid state, in a range of temperature lying between -15 degrees C. and the freezing point. Temperature measurements carried out in this range showed that suspensions were about equally infections whether the temperature at their centers dropped from 0 degrees C. to -15 degrees C. in 30 minutes or in 1 minute; when the drop occurred in 12 seconds or less, the suspensions became innocuous.
The Continuum Model of Selection in Human Tumors: General Paradigm or Niche Product?
Authors: Simon Leedham, Ian Tomlinson
Journal: Cancer Research (2012)

Berger and colleagues recently proposed a continuum model of how somatic mutations cause tumors to grow, thus supplementing the established binary models, such as oncogene activation and "two hits" at tumor suppressor loci. In the basic continuum model, decreases or increases in gene function, short of full inactivation or activation, impact linearly on cancer development. An extension, called the fail-safe model, envisaged an optimum level of gene derangement for tumor growth, but proposed that the cell gained protection from tumorigenesis because additional mutations caused excessive derangement. Most of the evidence in support of the continuum model came from Pten mutant mice rather than humans. In this article, we assess the validity and applicability of the continuum and fail-safe models. We suggest that the latter is of limited use: In part, it restates the existing "just right" of optimum intermediate gene derangement in tumorigenesis, and in part it is inherently implausible that a cell should avoid becoming cancerous only when it is some way down the road to that state. In contrast, the basic continuum model is a very useful addition to the other genetic models of tumorigenesis, especially in certain scenarios. Fittingly for a quantitative model, we propose that the continuum model is most likely to apply where multiple, cancer-promoting mutations have relatively small, additive effects, either through the well-established case of additive germline predisposition alleles or in a largely hypothetical situation where cancers may have acquired several somatic "mini-driver" mutations, each with weaker effects than classical tumor suppressors or fully activated oncogenes.
Antimalaria Drug Offers Antitumor Strategies
Authors: K. Hede
Journal: JNCI Journal of the National Cancer Institute (2011)

Q uinacrine, an old antimalaria drug given to millions of soldiers during World War II, is garnering new interest as a chemotherapeutic agent that targets two major cancer-promoting pathways — apparently with minimal toxicity to normal cells.Interest in the drug’s mechanism of action has also spawned a search for structural analogues culminating in a new class of compounds, dubbed curaxins, which appear to mimic how quinacrine works. Recent studies in Wafi k El-Deiry’s lab at the University of Pennsylvania with human colorectal and hepatocellular carcinoma show that quinacrine works synergistically with stalwarts of the chemotherapy arsenal as well as the newer targeted therapy sorafenib to delay tumor growth. In particular, El-Deiry noted a set of experiments he and his colleagues published in the Aug. 1, 2011, issue of Cancer Biology and Therapy that showed quinacrine synergized with sorafenib to nearly eliminate Mcl-1, a key oncogenic survival factor and known chemotherapy resistance factor, in HepG2 hepatocellular carcinoma cells. The group also showed that quinacrine administration greatly reduced high Mcl-1 levels in cells treated with adriamycin, 5-fl uorouracil, and gemcitabine, among other agents. The results were impressive enough to El-Deiry to immediately seek approval for a clinical trial combining capecitabine with quinacrine for patients with advanced colorectal cancer. El-Deiry said his group has written the clinical protocol, which the U.S. Food and Drug Administration is reviewing. He pointed out that few options remain when a colon cancer progresses after fi rstand second-line therapy. Furthermore, El-Deiry is disappointed with the lack of affordable options for patients with advanced disease. “Quinacrine has been used for more than 80 years, and there’s a lot of knowledge about it,” he said. “It’s not a very expensive drug. We need other options for our patients, and this one seems feasible.”
2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis
Authors: Désirée van der Heijde, Joachim Sieper, Walter P Maksymowych, Maxime Dougados, Rubén Burgos-Vargas, Robert Landewé, Martin Rudwaleit, Jürgen Braun
Journal: Annals of the Rheumatic Diseases (2011)

This paper presents the second update of the Assessment in SpondyloArthritis international Society (ASAS) consensus statement on the use of anti-tumour necrosis factor (anti-TNF) agents in patients with axial spondyloarthritis (SpA). A major change from the previous recommendations is that patients fulfilling the ASAS axial SpA criteria, which also include patients fulfilling the modified New York criteria for ankylosing spondylitis, can be treated with anti-TNF agents. This makes an earlier start in the disease process possible. A second major change is the mandatory pretreatment before anti-TNF agents can be started. All patients should have tried a minimum of two non-steroidal anti-inflammatory drugs for a minimum of 4 weeks in total. This is significantly shorter than the previous requirement of 3 months. As previously, patients with axial symptoms require no further pretreatment. Patients with symptomatic peripheral symptoms should normally have had an adequate therapeutic trial of a disease-modifying antirheumatic drug, preferably sulfasalazine. Sulfasalazine is no longer mandatory in this group of patients. Finally, efficacy should be evaluated after at least 12 weeks. The remaining recommendations stayed largely unchanged.
Tissue engineering of vascularised human liver organoids: study of morphology phenotypic expression and metabolomics of transitional co-cultures of hepatic/endothelial progenitors
Authors: L. J. Nelson, K. Burgess, M. Navarro, O. Tura, K. Samuel, P. C. Hayes, M. Turner, J. N. Plevris
Journal: Gut (2011)

<h3>Introduction</h3> Tissue architecture and hepatic cell morphology reflect the functional differentiation of the liver. Differentiated functions of hepatocytes, depend on complex, hetereotypic cell-cell/cell-matrix interactions mediated by cell adhesion molecules (CAMs) in a 3D microenvironment. Vascularisation of human hepatic tissue for therapeutic/pharmaceutical applications, requires knowledge of optimal trophic conditions to support different cell types and how these cells behave embedded in different biocompatible matrices. <h3>Methods</h3> The authors aimed to assess morphology, metabolic functionality and phenotypic expression of human progenitor EoCs (Endothelial outgrowth Cells) vascular microvessels, cocultured with hepatic C3A cells (C3As). EoC/C3A cocultures in different media and test biomatrices: Matrigel/MaxGel/Puramatrix (self-assembling nanofibres); and control standard 2D cultures (tissue culture plastic; TCP) were analysed following immunostaining using morphology (light/confocal microscopy); and flow cytometry. Metabolomics analysis of culture media provided a global picture of metabolic changes in response to hepatic/EoC coculture (vs reference C3A mono-cultures). <h3>Results</h3> Titration in standard 2D/TCP co-culture in various media showed a ratio of 3C3A:1EoC in Lonza EGM-2 medium was optimal. Cells retained phenotypic expression of differentiation markers: (1) Hepatic: Albumin, EpCAM, E-CAD; (2) EoC: CD146, CD31, CD105, VWF; as evidenced by flow cytometry/immunostaining. Metabolomics analysis of media (from 2D/TCP co-cultures), showed modulation of key hepatic metabolic intermediaries including: (1) Urea cycle: 50% enhancement of L-ornithine production; (2) Biosynthesis: Bile Acids: Enhanced Glycocholate; amino acid (eg, Taurine) utilisation; and Creatine production: (3) Antioxidants: co-culture ameliorated the requirement of high Glutathione antioxidant levels inherent to EoC monocultures. Test biomatrices under different 3D culture configurations, showed: (1) MaxGel sandwich culture promoted differentiated (cuboidal) morphology of C3As, but not EoCs; (2) Conversely, only EoCs overlaid on MaxGel formed differentiated (microvessel) structures; (3) Puramatrix supported 3D culture of C3As but not EoCs; (4) Matrigel supported only EoCs 3D microtubular structures. <h3>Conclusion</h3> This study proved informative for engineering of vascularised organoids for future clinical/pharmaceutical applications. Work in progress include comprehensive metabolomics analysis, flow cytometric profiling and combinatorial analysis of cell-supportive biomatrix configurations to further optimise 3D coculture.