tbuckley/cabot-search huggingface dataset:
Assessment and management of cannabis use disorders in primary care
Authors: A. R. Winstock, C. Ford, J. Witton
Journal: BMJ (2010)

#### Summary points

About a third of adults in the UK have tried cannabis, and 2.5 million people, mostly 16-29 year olds, have used it in the past year.1 Although most people who smoke cannabis will develop neither severe mental health problems nor dependence, regular use of cannabis may be associated with a range of health, emotional, behavioural, social, and legal problems, particularly in young, pregnant, and severely mentally ill people.2 3 The past decade has seen a shift in available cannabis preparations from resinous “hash” to intensively grown high potency herbal preparations, often referred to as skunk, which now dominates the UK market.4 Compared with traditional cannabis preparations, skunk tends to have higher levels of tetrahydrocannabinol, the main psychoactive constituent of cannabis, and lower levels of the anxiolytic cannabinoid cannabidiol. In January 2009 cannabis was returned to its original class B classification (from class C) under the UK Misuse of Drugs Act.

Despite high levels of use, only 6% of those seeking treatment for substance misuse in England cite cannabis as their …
Tissue Engineering: The Control of Mesenchymal Stem Cell Differentiation Using Dynamically Tunable Surface Microgrooves (Adv. Healthcare Mater. 10/2014)
Authors: Tao Gong, Kun Zhao, Guang Yang, Jinrong Li, Hongmei Chen, Yuping Chen, Shaobing Zhou
Journal: Advanced Healthcare Materials (2014)

A dynamically tunable smart topography surface based on a shape memory polymer is developed on page 1608 to mimic the endogenous cell culture microenvironment. By changing the surface topographic features and the resultant mechanical forces, S. Zhou and co-workers effectively direct stem cells to specifically differentiate towards myogenic lineage in the absence of any induction factors.
Late Results of Autogenous Vein Bypass Grafts in Femoropopliteal Arterial Occlusion
Authors: R. M. Baddeley, F. Ashton, G. Slaney, A. D. Barnes
Journal: BMJ (1970)

The outcome of 185 consecutive autogenous vein bypass grafts for femoro-popliteal occlusions carried out between January 1962 and June 1968 has been reviewed. One patient died at operation and 21 late deaths have occurred since. The overall five-year patency was 61.5%, but was much lower when the popliteal-tibial runoff arteries were diseased. Distal anastomosis of the graft to the popliteal artery below the level of the knee joint also impaired the results, and if this was performed with a graft of minimal diameter less than 5 mm. sustained patency was obtained in only a quarter of the limbs. Nevertheless, where major amputation was imminent owing to advanced ischaemia three out of four limbs were salvaged.
Abstract 2114: Docosahexaenoic acid induces degradation of human papillomavirus E6 and E7 oncoproteins through activation of the ROS-mediated ubiquitin-proteasome system in cervical cancer cells.
Authors: Kaipeng Jing, Soyeon Shin, Soyeon Jeong, Ji-Hoon Park, Kang-Sik Seo, Jun-Young Heo, Jeongsu Han, Jong-Il Park, Gi-Ryang Kweon, Seung-Kiel Park, Wan-Hee Yoon, Byung-Doo Hwang, Kyu Lim
Journal: Cancer Research (2013)

Abstract Sustained expression of high risk human papillomavirus (HR-HPV) E6/E7 oncogenes is essential for the maintenance of cervical cancer. We have previously reported that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, triggers apoptosis in HR-HPV positive cervical cancer cells. The aim of present study was to investigate whether and how the DHA-induced apoptosis is associated with modulation of E6/E7 viral oncoproteins in HR-HPV positive HeLa and SiHa cells. We found that DHA diminished E6/E7 protein levels in a time-dependent manner and restored the function of known E6/E7 binding targets, p53 and retinoblastoma (Rb) tumor suppressors. DHA increased the ubiquitination and proteasomal degradation of E6/E7 oncoproteins as well as three different ubiquitin-proteasome system (UPS) reporter substrates (GFP-CL1, GFP-ODC and UbG76V-GFP), supporting that DHA degrades E6/E7 viral proteins via the UPS. Using HeLa cells constitutively expressing UbG76V-GFP reporter, we confirmed these effects of DHA and further observed that similar to DHA, hydrogen peroxide (H2O2) was also able to accelerate E6/E7 degradation through promoting the UPS activity. In addition, reactive oxygen species (ROS) scavengers significantly prevented the UPS-mediated reduction in E6/E7 viral proteins and apoptosis caused by DHA and H2O2, suggesting that the augmented UPS activity and E6/E7 degradation caused by DHA depend on its effect on ROS generation. Together, our results show that DHA induces degradation of HPV E6/E7 oncoproteins through activation of the ROS-mediated UPS, and provide novel insights into the mechanism by which DHA exerts its inhibitory effect on virus-associated cancer. [This work was supported by the National Research Foundation of Korea (NRF) grant funded by Korea government (2012-0005767, 2012-0005456 and 2011-0003060)]. Citation Format: Kaipeng Jing, Soyeon Shin, Soyeon Jeong, Ji-Hoon Park, Kang-Sik Seo, Jun-Young Heo, Jeongsu Han, Jong-Il Park, Gi-Ryang Kweon, Seung-Kiel Park, Wan-Hee Yoon, Byung-Doo Hwang, Kyu Lim. Docosahexaenoic acid induces degradation of human papillomavirus E6 and E7 oncoproteins through activation of the ROS-mediated ubiquitin-proteasome system in cervical cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2114. doi:10.1158/1538-7445.AM2013-2114
Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia
Authors: F R Schuster, B Hubner, M Führer, O Eckermann, M Gombert, K Dornmair, V Binder, S Reuther, P Krell, T Keller, A Borkhardt
Journal: Blood Cancer Journal (2011)

One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA (n=10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response (n=6, CD8+ complexity scoring median 35.5, range 24-73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity (n=4, CD8+ complexity scoring median 109.5, range 82-124) always failed (P=0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation.
Spontaneous regression associated with apoptosis in a patient with acute-type adult T-cell leukemia
Authors: Kakushi Matsushita, Naomichi Arima, Hiroshi Fujiwara, Shiroh Hidaka, Hideo Ohtsubo, Kosei Arimura, Toshimasa Kukita, Midori Okamura, Chuwa Tei
Journal: American Journal of Hematology (1999)

We describe a 76-year-old man with acute-type adult T-cell leukemia, who demonstrated a spontaneous decrease in leukemic cell number, apparently coincident with apoptotic cell death. On admission the patient's white blood cell count was 38.9 × 109/l with 77% abnormal lymphocytes. He also had hypoproteinemia (4.3 g/dl) from protein losing enteropathy. After admission the leukemic cell count decreased without chemotherapy, reaching 5.9 × 109/l after 2 months. Studies of peripheral lymphocytes demonstrated appearance of the apoptotic cells and DNA ladder formation from the beginning of regression. Same truncated proviral DNA was recognized in primary ATL cells through the whole clinical course. The hypoproteinemia improved with intravenous nutrition, followed by increase of the leukemic cells. This case is the first report that demonstrates tumor-cell apoptosis induced clinical regression in adult T-cell leukemia. Further, we speculate that the hypoproteinemia may have been involved in the leukemic cell apoptosis. Am. J. Hematol. 61:144–148, 1999. © 1999 Wiley-Liss, Inc.
Journey of a patient editor
Authors: T. Richards
Journal: BMJ (2013)

Nine years ago the <i>BMJ</i>’s <b>Tessa Richards</b> underwent thoraco-abdominal surgery for adrenal cancer, followed by further surgery to remove metastases. Now the senior editor in charge of the journal’s patient partnership agenda, she reflects on how her own experience of illness and recovery, and of joining the ranks of patients who survive the odds, have shaped her understanding of the patient perspective
Analyzing the Effect of State Legislation on Health Care Utilization for Children With Concussion
Authors: Teresa B. Gibson, Stanley A. Herring, Jeffrey S. Kutcher, Steven P. Broglio
Journal: JAMA Pediatrics (2014)

In 2009, Washington State enacted legislation outlining the medical care of children and adolescents with concussion (ie, the Lystedt Law), with all other states and Washington, DC passing legislation by January 2014.To evaluate the effect of concussion laws on health care utilization rates from January 1, 2006, through June 30, 2012, in states with and without legislation.For commercially insured children aged 12 to 18 years from all 50 states and DC from January 1, 2006, through June 30, 2009, we examined the following: (1) prelegislation trends in concussion-related health care utilization from January 1, 2006, through June 30, 2009, (2) postlegislation trends in states without concussion legislation, and (3) the effect of state concussion laws on trends in states with concussion legislation in effect by means of negative binomial multivariable estimation with state and time fixed effects.Concussion diagnosis.Emergency department and related health care utilization rates for concussion.Between academic school years 2008-2009 and 2011-2012, states with legislation experienced a 92% increase in concussion-related health care utilization, while states without legislation had a 75% overall increase in concussion-related health care utilization during the same period. In the multivariable fixed-effects models, controlling for differences across states, rates of treated concussion in states without legislation were 7% higher in the 2009-2010 school year, 20% higher in the 2010-2011 school year, and 34% higher in the 2011-2012 school year compared with the prelegislation trends (2005-2009) (all P < .01). During the same period, states with concussion laws demonstrated a 10% higher concussion-related health care utilization rate compared with states without laws (P < .01).Increased health care utilization rates among children with concussion in the United States are both directly and indirectly related to concussion legislation. A portion of the increased rates (60%) in states without legislation is attributable to an ongoing upward trend demonstrated before enactment of the first state law in 2009. The remaining 40% increase in these states is thought to have resulted from elevated awareness brought about by heightened local and national media attention. Concussion legislation has had a seemingly positive effect on health care utilization, but the overall increase can also be attributed to increased injury awareness.
Skin Rashes with Penicillin Therapy: Current Management
Authors: Bernard B. Levine
Journal: New England Journal of Medicine (1972)

Administration of penicillins and cephalosporins is associated with a variety of adverse reactions —e.g., anaphylaxis, drug fever, Coombs-positive hemolytic reactions, agranulocytosis, interstitial nephritis and drug rashes. Of these, drug rashes are the most common. Urticarial, erythematous or morbilliform (also termed maculopapular or exanthematic) eruptions are seen most often. More rarely associated with penicillin therapy are erythema nodosum, erythema multiforme and purpuric, eczematous or vesiculobullous eruptions. These clinical lesions have been illustrated in color in an article by Harris and Baer.1 Drug rashes occur in 1 to 7 per cent of patient courses of penicillins and are responsible for a number . . .
UV-B–triggered induction of vitamin D3 metabolism differentially affects antimicrobial peptide expression in keratinocytes
Authors: Mark Peric, Bodo Lehmann, Gabriela Vashina, Yvonne Dombrowski, Sarah Koglin, Michael Meurer, Thomas Ruzicka, Jürgen Schauber
Journal: Journal of Allergy and Clinical Immunology (2010)
STUDIES OF TISSUE MAINTENANCE
Authors: H. P. Gilding
Journal: The Journal of Experimental Medicine (1929)

The vascular readjustments in compensation for a greatly reduced blood bulk affect the service rendered by the blood to the gastrointestinal tract and liver far less than they do that to the skin and muscles. Into these latter tissues india ink is carried almost not at all, whereas it circulates in quantity through the capillaries of the bowel and liver. Evidently vaso-constriction is much less effective in these viscera. Nowhere in them does one find a patchy ischemia like that so wide-spread in the peripheral tissues. Blood service is maintained to the same extent everywhere throughout the liver even when one of its two sources (hepatic artery or portal vein) is obstructed, and the intrahepatic blood pressure brought very low. A pronounced patchy ischemia of the stomach and large bowel can be induced by intravenous injection into normal animals of sufficient epinephrin to cause the systemic blood pressure to mount to an abnormally high level. Pituitrin used in the same way has a greater effect; blood service to the organs mentioned may be completely abolished by means of it. In both instances, though, service to the small gut and liver is still excellently and evenly maintained.
Expectant Treatment of Perforated Ulcer
Authors: B. B. Freshwater
Journal: BMJ (1951)

<h3>OBJECTIVE</h3> To identify the specific nature of the neurocognitive impairments of eosinophilia-myalgia syndrome (EMS) in an unselected population, and to present longitudinal patterns. <h3>METHODS</h3> A consecutive sample of 23 patients with EMS and 18 age and education matched control subjects were assessed on a comprehensive neuropsycho- logical battery. Longitudinal results were gathered from six patients. <h3>RESULTS</h3> Neurocognitive impairments were found which represent a subset of deficits reported in previous group and case study reports. Deficits were limited to complex visual memory, conceptual set shifting, and attention, which suggest a selective dysexecutive syndrome. The motor slowing and verbal memory deficits previously reported were not found. Although depression, fatigue, sleep deprivation, and pain were significant symptoms, they were unassociated with deficits with the exception of an association of depression with one deficit. There was no pattern of overall decline over time in a subset of the group, although considerable heterogeneity in the longitudinal patterns of neurocognitive tests was found. Abnormalities of white matter appeared in the MRI of eight of 12 patients. <h3>CONCLUSIONS</h3> The neurocognitive and neuroimaging findings contribute to the evidence which indicates that the neural substrate of EMS is white matter damage.
Experimental Renal Disease Induced by DNA—Anti-DNA Immune Complexes
Authors: Pier Giorgio Natali, Eng M. Tan
Journal: Journal of Clinical Investigation (1972)

Rabbits immunized with ultraviolet-irradiated DNA (UV-DNA) produced high titers of serum antibody. This experimental model was studied to determine if injection of antigen (UV-DNA) intravenously into immunized animals would induce glomerulonephritis and proteinuria. Proteinuria was observed several days after the start of daily intravenous injections into immunized animals and was sustained as long as injections were continued, but fell to normal values after stopping antigen administration. The kidneys showed glomerulitis sometimes associated with focal proliferative lesions, and immunofluorescence showed rabbit Ig and C3 in glomeruli. By electron microscopy, electron-dense subendothelial deposits were seen. Sucrose density gradient analyses of sera immediately after antigen injections suggested the presence of immune complexes of DNA and antibody since both heavy sedimenting and 7S Ig were detected. After digestion with deoxyribonuclease rabbit Ig could be found only in the 7S sedimenting fractions. Intravenous injection of UV-DNA into normal, nonimmune animals did not produce heavy sedimenting Ig or abnormal sedimentation patterns. These studies with an experimental model might provide insight into pathogenetic mechanisms operating in systemic lupus erythematosus where the importance of DNA-anti-DNA immune complexes have been documented. The studies suggested that gradual accumulation of DNA immune complexes in glomeruli might be one mechanism causing renal functional abnormalities.
Peginterferon alfa-2b plus ribavirin for naïve patients with genotype 1 chronic hepatitis C: a randomized controlled trial
Authors: Savino Bruno, Calogero Cammà, Vito Di Marco, Mariagrazia Rumi, Maria Vinci, Mario Camozzi, Chiara Rebucci, Danilo Di Bona, Massimo Colombo, Antonio Craxì, Mario U. Mondelli, Giovanbattista Pinzello
Journal: Journal of Hepatology (2004)
Impact of macrolide therapy on mortality in severe sepsis caused by pneumonia
Authors: M. M. van der Eerden, W. G. Boersma
Journal: European Respiratory Journal (2009)

Impact of macrolide therapy on mortality in severe sepsis caused by pneumoniaTo the Editors:We read with interest the recent paper by RESTREPO et al. [1] who reported that adding a macrolide to the antibiotic regimen in patients with community-acquired pneumonia (CAP) and severe sepsis resulted in lower mortality.Their data are very promising.However, we have a concern regarding the recommendations to implement macrolides as standard treatment for CAP.
328. An Orthotopic Murine Model of Advanced Breast Cancer for Imaging and Comparison of Targeting Moieties
Authors: Tuuli Ranki, Anna Kanerva, Karl von Smitten, Merja Sarkioja, Lotta Kangasniemi, Mari Raki, Pirjo Laakkonen, Hongju Wu, David T. Curiel, Steven Goodison, Akseli Hemminki
Journal: Molecular Therapy (2005)

Top of pageAbstract
Background: Serotype 5 adenovirus (Ad5) displays high gene transfer efficacy to cells with abundant coxsackie-adenovirus receptor (CAR) expression. However, CAR is variably and often poorly expressed in many tumor types. This has not been comprehensively studied in the context of breast cancer, the most common cancer in women. Fortunately, adenoviruses can be modified to attach to other cellular receptors in order to circumvent the dependence on CAR and to achieve enhanced gene transfer to tumors. Ad5.pK7 (GL) (contains GFP- and luciferase genes) is modified with a polylysine motif allowing CAR independent Ad binding to cell-surface receptors with polyanionic motifs such as heparan sulphate. Ad5lucRGD contains an RGD-4C motif allowing binding to cellular integrins, Ad5.RGD.pK7 (GL) contains both of these modifications and Ad5/3luc1 has a chimeric fiber with the serotype 3 knob and binds to a yet unknown receptor distinct from CAR. Our hypothesis was that we could enhance the infectivity of breast cancer cell lines, clinical samples and orthotopic xenografts by using these targeting moieties.

Methods: Gene transfer was studied with firefly luciferase expressing viruses. We also studied cell killing by the respective oncolytic, conditionally replicating adenoviruses (CRAds), featuring a 24 bp deletion in the E1A region, which leads to selective replication in Rb-p16 pathway defective cells. An orthotopic murine model was created by injections of GFP positive MDA-MB-435 cells into mammary fat pads of mice.

Results: Some of the modified viruses displayed improved gene transfer to cancer cells in vitro and showed enhanced oncolytic activity over a virus with a wild type capsid. Capsid modified viruses also showed enhanced gene transfer to tumors in a murine model of advanced breast cancer.

Conclusions: Mature in vitro and in vivo data will be presented and discussed. In vivo data will include imaging in an orthotopic murine model of advanced breast cancer.
Regulation of Parathyroid Hormone Secretion*
Authors: SUSAN L. POCOTTE, GERALD EHRENSTEIN, LORRAINE A. FITZPATRICK
Journal: Endocrine Reviews (1991)

PARATHYROID hormone (PTH) maintains calcium homeostasis through its effects on target tissues, bone, and kidney. The parathyroid cell is unusual in that decreasing concentrations of calcium stimulate secretion of PTH, and increasing concentrations of calcium inhibit secretion of PTH. Thus, this cell, which is responsible for the critical maintenance of ionized blood calcium levels, is, in turn, regulated by calcium itself. The inverse relationship between extracellular calcium concentration and PTH secretion has been well established experimentally. However, the cellular mechanisms responsible for this relationship are poorly understood. This review will focus on several questions relating to the regulation of PTH secretion. Because of the physiological importance of the interaction between serum calcium and PTH, we will emphasize regulation of PTH by calcium. The role of other regulators will also be considered. The main questions we will address are: Does intracellular or extracellular calcium regulate PTH secretion? What are the mechanisms that allow extracellular calcium to influence the intracellular calcium concentration? What is the mechanism for the inverse dependence of secretion on calcium concentration? What is the role of cAMP and other second messengers in regulating PTH secretion?
Immunophenotypic and genotypic characterization of lymphomatoid papulosis
Authors: Jeff D. Parks, Mark S. Synovec, Aneal S. Masih, Suzanne W. Braddock, Hirokazu Nakamine, Warren G. Sanger, Douglas S. Harrington, Dennis D. Weisenburger
Journal: Journal of the American Academy of Dermatology (1992)
Heterosexual transmission of HIV in injecting drug users.
Authors: P J Ronald, J R Robertson, R Wyld, R Weightman
Journal: BMJ (1993)

accord with the view that longer preregistration training would exacerbate the problems house officers face.21Less than a quarter of respondents would encourage potential medical students to enter the profession, although over half would recommend their job to a friend. CONCLUSIONThere are serious deficiencies in the preparation of house officers for their role and in the education they receive in post.They are often subject to excessive and inappropriate demands, working rotas incompatible with NHS Management Executive targets in hospitals that many of them regard as insecure.Unsurprisingly, few house officers would encourage others to take up medicine.