tbuckley/cabot-search huggingface dataset:
PPARγ<scp>AND</scp>G<scp>LUCOSE</scp>H<scp>OMEOSTASIS</scp>
Authors: Frédéric Picard, Johan Auwerx
Journal: Annual Review of Nutrition (2002)

▪ Abstract Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor involved in the control of metabolism. Research on PPARγ is oriented towards understanding its role in insulin sensitization, which was inspired by the discovery that antidiabetic agents, the thiazolidinediones, were agonists for PPARγ. PPARγ stimulation improves glucose tolerance and insulin sensitivity in type 2 diabetic patients and in animal models of insulin resistance through mechanisms that are incompletely understood. Upon activation, PPARγ heterodimerizes with retinoid X receptor, recruits specific cofactors, and binds to responsive DNA elements, thereby stimulating the transcription of target genes. Because PPARγ is highly enriched in adipose tissue and because of its major role in adipocyte differentiation, it is thought that the effects of PPARγ in adipose tissue are crucial to explain its role in insulin sensitization, but recent studies have highlighted the contribution of other tissues as well. Although relatively potent for their insulin-sensitizing action, currently marketed PPARγ activators have some important undesirable side effects. These concerns led to the discovery of new ligands with potent antidiabetic properties but devoid of certain of these side effects. Data from human genetic studies and from PPARγ heterozygous knockout mice indicate that a reduction in PPARγ activity could paradoxically improve insulin sensitivity. These findings suggest that modulation of PPARγ activity by partial agonists or compounds that affect cofactor recruitment might hold promise for the treatment of insulin resistance.
Use and Misuse of an Accident and Emergency Department in the East End of London
Authors: Anthony G Davison, A C C Hildrey, M A Floyer
Journal: Journal of the Royal Society of Medicine (1983)

A study was made of all 587 new patients attending an accident and emergency department in the East End of London during one week. Two hundred and twenty-six (39%) cases were not accidents or emergencies; of these, 67% were self-referrals who had not previously seen their general practitioner (GP) and 21% were self-referrals who had previously seen their GP. The four main reasons that these self-referred patients had for attending were that they thought their condition needed immediate attention; they were insufficiently organized to see their GP; they were not registered with a GP; or they wanted a second opinion. Twenty-eight (12%) of the cases which were not accidents or emergencies were referred by a GP. Sixty-nine (12%) of all cases were not registered with a GP. The frequency of cases who were not accidents or emergencies was significantly higher in those not registered than in those registered (0.01 greater than P greater than 0.001). Nineteen (3%) patients were living rough or in hostels. Little abuse of the ambulance service was found.
ABC of wound healing:Infections
Authors: Brendan Healy, Andrew Freedman
Journal: BMJ (2006)

Despite optimal treatment some wounds are slow to heal. The challenge clinically and microbiologically is to identify those wounds in which healing is impaired as a result of infection or heavy bacterial burden and in which systemic or topical antimicrobial treatment will be of benefit.

Staphylococci and streptococci are the most commonly encountered pathogenic organisms in community acquired superficial wounds. More unusual organisms may be found in bite wounds, and these reflect the source of the bite. Pathogenic organisms causing surgical wound infections vary according to the anatomical site of surgery. Antibiotic resistant organisms, such as methicillin resistant Staphylococcus aureus (MRSA), are more commonly encountered, reflecting the hospital flora.



It is inappropriate to swab all wounds: swabs should be taken only from overtly infected wounds and from wounds that are deteriorating, increasing in size, or failing to make satisfactory progress despite an optimal environment for wound healing. Indicators of wound infection include redness, swelling, purulent exudate, smell, pain, and systemic illness in the absence of other foci. Subtle signs of local wound infection include unhealthy “foamy” granulation tissue, contact bleeding, tissue breakdown, and epithelial bridging.

Superficial wound swabs-The ease of obtaining and processing superficial wound swabs, combined with their relatively low cost and non-invasive nature, make them in most instances the most appropriate method for wound sampling. Organisms cultured from a superficial swab may, however, simply reflect the colonising bacterial flora and are not always representative of the pathogenic organisms invading deeper tissue. This is particularly relevant to deep surgical and deep penetrating wounds in which infection from internal sources may occur.

Tissue and pus-Tissue or pus, or both, should be collected whenever possible, as growth from these samples is more representative of pathogenic flora. These are amenable to quantitative microbiological analysis and other techniques used to improve the diagnostic …
Biomarkers in COPD exacerbation, the role of adiponectin
Authors: Vlasios Vitsas, Matina Kardara, Antonia Koutsoukou, Pinelopi Michalopoulou, Stylianos Orfanos, Georgios Tsoukalas, Anastasia Kotanidou
Journal: European Respiratory Journal (2014)

Introduction:  COPD is a condition of global importance, characterised by accelerated lung function decline and an abnormal inflammatory response. Exacerbations account for much of the morbidity and the mortality in COPD. Adiponectin is a protein that is synthesised and secreted primarily by white adipose tissue.   Objectives:  To record and analyse parameters such as bomarkers (adiponectin, IL6, IL8 and others), lung functions and dyspnea level on the 1st day of a COPD exacerbation, at discharge and 6 weeks after. These are preliminary results of the study.   Methods:  20 patints (mean age 67,5 years) which were hospitalised for exacerbation of COPD are included so far in the study. Biomarkers such as adiponectin, leucocytes, IL6, IL8 and CRP were measured at admission, at discharge and 6 weeks after discharge. Lung function and dyspnea level were studied and measured at discharge and 6 weeks later.    Results:  A trend for decline was observed (p=o,10) for adiponectin levels at discharge and 6 weeks after. The adiponectin levels in patients serum with acute exacerbation of COPD before discharge from the hospital (mean 6,47μg/ml ±2,94) were higher than those measured from the same patients 6 weeks after discharge (stable COPD) (mean 6,13 ±3,71). Statistical significant differences were observed at the levels of CRP at admission and discharge (p   Conclusion:  Even though the study is still at an early stage, there are useful conclusions to be made. Adiponectin presents a decreasing trend 6 weeks after the exacerbation which indicates that it may be a valuable biomarker for the assessment of COPD severity along with FEV1and CRP.
Blue–Black Trachea as a Result of Minocycline-induced Hyperpigmentation
Authors: Takanori Asakura, Shigenari Nukaga, Ho Namkoong, Kazuma Yagi, Shoji Suzuki, Makoto Ishii, Sadatomo Tasaka, Tomoko Betsuyaku, Naoki Hasegawa
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

A 61-year-old woman presented with a blue–black discoloration of the skin, ears, and nails that had slowly progressed over the last three years. Five years previously, she was diagnosed with Mycobacterium abscessus pulmonary disease, and she had been receiving long-term multiple antimicrobial therapies, including minocycline (100 mg, twice a day). On admission, a physical examination indicated blue–black hyperpigmentation of the nail beds, gingiva, teeth, and back portion of the pinna of the ears (Figure 1). Bronchoscopy was performed to evaluate disease activity, which indicated the change in the color of visible tracheal cartilage to blue–black (Figure 2A indicates condition 5 yr previously, Figure 2B indicates current condition). Minocycline administration was discontinued, as the disease was presumed to be stable. The hyperpigmentation improved after 6 months. To our knowledge, this is the first report describing the hyperpigmentation of tracheal cartilages because of minocycline administration. Various etiologies have been reported for hyperpigmentation of the airway, including congenital disease, inborn errors of
Quality of Life in Palliative Cancer Care: Results From a Cluster Randomized Trial
Authors: Marit S. Jordhøy, Peter Fayers, Jon Håvard Loge, Marianne Ahlner-Elmqvist, Stein Kaasa
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To assess the impact of comprehensive palliative care on patients’ quality of life. The intervention was based on cooperation between a palliative medicine unit and the community service and was compared with conventional care. PATIENTS AND METHODS: A cluster randomized trial was carried out, with community health care districts defined as the clusters. Patients from these districts who had malignant disease and survival expectancy between 2 to 9 months were entered onto the trial. The main quality-of-life end points were physical and emotional functioning, pain, and psychologic distress assessed monthly by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire and Impact of Event scale (IES). In total, 235 intervention patients and 199 controls were included. RESULTS: During the initial 4 months of follow-up, the compliance was good (72%) and comparable among treatment groups. No significant differences on any of the quality-of-life scores were found. At later assessments and for scores that were made within 3 months before death, there was also no consistent tendency in favor of any treatment group on the main outcomes or other EORTC QLQ-C30 scales/items. CONCLUSION: A general program of palliative care may be important to ensure flexibility and to meet the needs of terminally ill patients. However, to achieve improvements on a group level of the various dimensions of quality of life, specific interventions directed toward specific symptoms or problems may have to be defined, evaluated, and included in the program.
The efficacy of inhaled fluticasone furoate (FF) and vilanterol (VI) administered in combination in asthma is comparable when administered in the morning or evening
Authors: Rodger Kempsford, Amanda Oliver, Lee Tombs, Jo Bal
Journal: European Respiratory Journal (2012)

Introduction:  The novel corticosteroid FF and long-acting beta 2  agonist VI combination (FF/VI) is being developed as a once-daily inhaled treatment for asthma and COPD.   Objectives:  To investigate the effect of time of day of dosing (AM or PM) on the efficacy of FF/VI (100/25mcg).   Methods:  Single centre, randomised, double-blind, placebo-controlled, three-way crossover study. Subjects with persistent asthma [N=26; 24–64 years] received FF/VI (AM or PM) or matching placebo (P) once daily for 14(±2) days. FEV 1  (0–24h weighted mean and pre-treatment [AM and PM]) was determined after the Day 14 PM dose together with pre-treatment [AM and PM] PEF on Days 1–12.   Results:  FF/VI administered AM or PM produced clinically significant increases in weighted mean FEV 1 : the differences [95% CI] from P were 377mL [293, 462] and 422mL [337, 507], respectively; the difference between AM and PM dosing was –44mL [–125, 36]. Pre-treatment AM FEV 1  differences [95% CI] from P were 403mL [272, 533] and 496mL [369, 624] after AM and PM dosing, respectively; the treatment difference was –94mL [–221, 34]. Pre-treatment PM FEV 1  differences [95% CI] from P were 275mL [169, 380] and 309mL [205, 413] after AM and PM dosing, respectively; the treatment difference was –34mL [–138, 70]. FF/VI (AM or PM) produced rapid increases in PEF with the full effect apparent after the first dose and maintained throughout the 14 day treatment period.   Conclusion:  The efficacy of FF/VI (100/25mcg) was comparable when dosed in the morning or evening in subjects with persistent asthma.  Funded by GSK (HZA114624; NCT01287065).
Defining Burkitt’s lymphoma (BL) with cytogenetics: LY10, a prospective clinicopathological study of dose-reduced (dr) CODOX-M/IVAC in patients with 100% Ki-67 staining B-cell non-Hodgkin’s lymphoma (NHL)
Authors: J. Walewski, G. Mead, A. Jack, S. Barrans, J. Radford, S. Clawson, S. Stenning, W. Qian
Journal: Journal of Clinical Oncology (2006)

7557 Background: Previous studies suggest that CODOX-M/IVAC is effective therapy for BL (Ann Onc 2002 13:1264–74), however the diagnosis of BL in this and other studies was not based on modern immunochemistry and cytogenetics and is unreliable. To re-evaluate this question we prospectively studied a population of patients (pts) with aggressive B-cell lymphoma (100% Ki-67+) uniformly treated with dr CODOX-M/IVAC. Methods: Pts ≤65 years with B-cell lymphomas showing 100% Ki-67, considered fit for chemotherapy, received either dr CODOX-M x 3 or dr CODOX-M/IVAC x 4 according to a modified international prognostic index (IPI). Chemotherapy was modified by methotrexate dose reduction to 3g/m 2 . Pts &gt;65 years had further dose reductions; unfit pts were studied pathologically only. Tumours were characterised using both an extended panel of antibodies and interphase FISH on paraffin sections for the presence of the C-MYC and BCL-2 rearrangements. Results: Of 126 pts reviewed centrally, 5 were ineligible; 53 were diagnosed as BL, each based on the combination of the presence of re-arrangement of C-MYC as a sole abnormality, germinal centre phenotype and p53 abnormality. The final 68 cases were highly heterogenous with respect to tumour phenotype and cytogenetics and were diagnosed as diffuse large B-cell lymphoma (DLBCL). Median age (all pts) was 44 years (range 17–83), with 23 aged &gt;65. Compared with the DLBCL pts, BL pts were significantly younger (mean 38yrs vs 53 yrs, p &lt; 0.001), had more marrow involvement (45% vs 24%, p = 0.02) and male predominance (83% vs 65%, p = 0.03). Of 104 pts entered into the clincal study, 32 pts (10 BL, 22 DLBCL, IPI 0,1) received dr CODOX-M x 3 and 72 (39 BL, 33 DLBCL, IPI &gt;1) received dr CODOX-M/IVAC x 4. With median follow-up of 15 months (range 1 to 37), 1 year progression-free survival was 58%, 95% CI 48%-68% (54% BL vs 62% DLBCL) and 1 year survival 61% 95% CI 51%-71% (55% BL vs 66% DLBC). Conclusions: The study shows Ki67 is not an accurate approach to the diagnosis of BL and the use of immunocytochemistry and FISH is essential. BL and DLBCL as defined differ markedly clinically. Preliminary data suggest that dr CODOX-M/IVAC has similar activity in both histologies. No significant financial relationships to disclose.
Exosome-mediated microRNA signaling from breast cancer cells is altered by the anti-angiogenesis agent docosahexaenoic acid (DHA)
Authors: Bethany N. Hannafon, Karla J. Carpenter, William L. Berry, Ralf Janknecht, William C. Dooley, Wei-Qun Ding
Journal: Molecular Cancer (2015)

Docosahexaenoic acid (DHA) is a natural compound with anticancer and anti-angiogenesis activity that is currently under investigation as both a preventative agent and an adjuvant to breast cancer therapy. However, the precise mechanisms of DHA's anticancer activities are unclear. It is understood that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are extracellular vesicles that are important mediators of intercellular communication and play a role in promoting angiogenesis. However, very little is known about the contribution of breast cancer exosomes to tumor angiogenesis or whether exosomes can mediate DHA's anticancer action.Exosomes were collected from MCF7 and MDA-MB-231 breast cancer cells after treatment with DHA. We observed an increase in exosome secretion and exosome microRNA contents from the DHA-treated cells. The expression of 83 microRNAs in the MCF7 exosomes was altered by DHA (>2-fold). The most abundant exosome microRNAs (let-7a, miR-23b, miR-27a/b, miR-21, let-7, and miR-320b) are known to have anti-cancer and/or anti-angiogenic activity. These microRNAs were also increased by DHA treatment in the exosomes from other breast cancer lines (MDA-MB-231, ZR751 and BT20), but not in exosomes from normal breast cells (MCF10A). When DHA-treated MCF7 cells were co-cultured with or their exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in the endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, suggesting that the microRNAs transferred by exosomes mediate DHA's anti-angiogenic action. These effects could be reversed by knockdown of the Rab GTPase, Rab27A, which controls exosome release.We conclude that DHA alters breast cancer exosome secretion and microRNA contents, which leads to the inhibition of angiogenesis. Our data demonstrate that breast cancer exosome signaling can be targeted to inhibit tumor angiogenesis and provide new insight into DHA's anticancer action, further supporting its use in cancer therapy.
Age-Specific Reduction in Breast Cancer Mortality by Screening: An Analysis of the Results of the Health Insurance Plan of Greater New York Study<xref ref-type="fn" rid="FN1">2</xref>
Authors: J D Habbema, G J van Oortmarssen, D J van Putten, J T Lubbe, P J van der Maas
Journal: JNCI Journal of the National Cancer Institute (1986)

The 14-year follow-up mortality results from the randomized breast cancer screening trial of the Health Insurance Plan of Greater New York (HIP) were analyzed with respect to the problem of age-specific screening effects. Mortality reduction was measured in three different ways and appears to be homogeneous across age groups. This finding challenges the widespread opinion that the results of the HIP study support the conclusion that breast cancer screening is not effective below age 50.
Effect of Two Disinfectant Treatments on Laboratory Analyses
Authors: M J Ball
Journal: Journal of the Royal Society of Medicine (1987)

Inactivation of human immunodeficiency virus (HIV), the retrovirus associated with the acquired immune deficiency syndrome (AIDS), can be achieved both by heating at 56°C and by chemical disinfection with beta-propiolactone (BPL). Such treatment of specimens from patients with suspected AIDS or antibodies to HIV could reduce any occupational risk to laboratory staff. This study demonstrates the effects of these treatments on laboratory analyses. Heat treatment of plasma caused clinically insignificant alteration in the results of electrolyte, urea, creatinine, albumin and glucose concentration, but significant alteration to total protein estimation and the activities of many enzymes. Haemolysis and cell agglutination occurred in many specimens of whole blood, making them unsuitable for haematological analyses. BPL caused less reduction of enzyme activities, and assay of many analytes, including electrolytes, plasma proteins, haemoglobin, white cell and platelet counts, was not significantly affected.
Virus Production in Rat Tumors Induced by Chicken Sarcoma Virus
Authors: C. Altaner, F. Svec
Journal: JNCI Journal of the National Cancer Institute (1966)

The RBI tumor, induced in rats with the chicken virus strain B77, was transferred with cell-free filtrates to chickens and ducks. After serial transplantation in rats for 32 months (25 passages), the average virus content was 2.84 × 103 ED50/g of tumor substance. Induced tumors RBIV and RBX, in the 46th and 24th passages, were transferred with intact cells to chicks. The effects of various physicochemical treatments of the RBI virus preparations are described, which indicate that the intact virus particle is transferred in an infectious form. The treatments included: temperatures of −70, −60, 20, 37, and 56 C; lyophilization; freeze-thaw cycles; formalin; ethanol; ether; deoxycholate; trypsin; ribonuclease; deoxyribonuclease; and osmotic shock. On the basis of neutralization reactions, the immunological properties of the RBI virus from rat tumor cells differed from those of the original chicken line B77 that induced the tumors. The RBI virus adapted to rat tumor cell. The increased induction capacity of this virus was determined by the viral envelope. The results show that in the rat tumor cell it is possible to replicate an intact infectious virus particle, pathogenic to chicks and ducks.
Grade 3 nausea, vomiting, and myelosuppression or progressive, metastatic sarcoma?
Authors: R S Benjamin
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.6.833 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3295127 Grade 3 nausea, vomiting, and myelosuppression or progressive, metastatic sarcoma? R S BenjaminxR S BenjaminSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.6.833 First Page PDF © 1987 by American Society of Clinical Oncology
Karyotype and Polyoma Virus Sensitivity in Clones Isolated From a Polyoma-Induced Mouse Tumor<xref ref-type="fn" rid="FN2">2</xref>
Authors: K. E. Hellström, I. Hellström, H. O. Sjögren
Journal: JNCI Journal of the National Cancer Institute (1964)

A karyological study was made on 14 tumor lines established from single-cell clones. These lines were isolated from a polyoma-induced mouse tumor and differed from each other in sensitivity to the cytopathogenic effect of polyoma virus. The data obtained suggest a relationship between karyotype and polyoma virus sensitivity of the tumor lines studied, which indicates that polyoma virus sensitivity may vary with cell genotype.
Verapamil with mitoxantrone for advanced ovarian cancer: A negative phase II trial
Authors: A.M. Hendrick, A.L. Harris, B.M.J. Cantwell
Journal: Annals of Oncology (1991)

Fourteen patients with advanced epithelial ovarian cancer were treated with oral verapamil 240 to 480 mg daily for 3 days and intravenous mitoxantrone 12 to 14 mg/m2 on the second days of verapamil administration. Courses were repeated at 21 day intervals to a maximum of 4 courses. Most patients had cancers refractory to prior cisplatin or carboplatin, or had cancers which recurred quickly after such treatments. This poor prognostic profile of patients probably accounted for the lack of objective responses to verapamil plus mitoxantrone. Despite maximally tolerated daily oral verapamil doses (480 mg daily) our inability to achieve in vivo levels of verapamil that in vitro have an optimum cytotoxic potentiating effect mitigate against further clinical exploration of verapamil as a sole enhancing agent.
Lentigo maligna melanoma has no better prognosis than other types of melanoma.
Authors: H K Koh, E Michalik, A J Sober, R A Lew, C L Day, W Clark, M C Mihm, A W Kopf, M S Blois, T B Fitzpatrick
Journal: Journal of Clinical Oncology (1984)

We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.