tbuckley/cabot-search huggingface dataset:
Biophysical and Physiological Effects of Solar Radiation on Human Skin
Authors: Alex Anstey
Journal: British Journal of Dermatology (2008)

Journal Article Biophysical and Physiological Effects of Solar Radiation on Human Skin Get access Alex Anstey Alex Anstey Royal Gwent Hospital, Cardiff Road, Newport, Gwent NP9 2UB, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 160, Issue 1, 1 January 2009, Page 227, https://doi.org/10.1111/j.1365-2133.2008.08913.x Published: 01 January 2009
Toxicity of Sunitinib Plus Bevacizumab in Renal Cell Carcinoma
Authors: Brian I. Rini, Jorge A. Garcia, Matthew M. Cooney, Paul Elson, Allison Tyler, Kristi Beatty, Joseph Bokar, Percy Ivy, Helen X. Chen, Afshin Dowlati, Robert Dreicer
Journal: Journal of Clinical Oncology (2010)
Definitely not acceptable: drug company sues journal over review
Authors: Ike Iheanacho
Journal: BMJ (2011)

With a dismissive kick a cartoon man in a ridiculous hat sends a small drug capsule flying. Questionable frivolity in a serious medical publication, some might say. But they’d be wrong. Trivial as it may look, this iconic image makes a crucial point.

It’s the device used by France’s La Revue Prescrire (and its English language sister Prescrire International ) to tag a therapeutic product as “not acceptable”—in other words “without evident benefit but with real or potential disadvantages.” And it’s just the lowest of seven potential ratings. For example, at the other extreme there’s “bravo,” where the man …
The role of mast cells in atopy: what can we learn from canine models? A thorough review of the biology of mast cells in canine and human systems
Authors: F. De Mora, A. Puigdemont, R. Torres
Journal: British Journal of Dermatology (2006)

Mast cell research has largely focused on the role of these cells in the early phase of allergic reactions. However, their involvement may well extend beyond this stage, and even reach across nonallergic conditions. Mast cells from different sources have helped advance our knowledge of their biology. Although in vitro and in vivo research in this area has mainly focused on humans, such studies are limited by the extent to which cells from certain human tissues and/or human patients can be collected or studied. While rodents also provide valuable models with which to further our understanding of the behaviour of mast cells and their contribution to allergy, reported differences between human and murine mast cells, and, in some instances, the limitations of in vivo rodent models of mast cell‐mediated allergic conditions, preclude their use. In this review, we introduce a relatively unknown mast cell population, that of the dog. Canine mast cells display many phenotypic and functional similarities with their human counterparts, and dogs develop spontaneous and induced allergic diseases that share clinical and pathophysiological features with the human condition. Therefore, the use of canine cells can shed light on the general role of mast cells, particularly in relation to allergic diseases given the potential of in vivo dog models within this field. Here we provide a detailed review of the data reported from in vitro and in vivo studies of canine mast cells, and compare them with results obtained in human systems. We also highlight direct evidence of the mast cell contribution to canine atopy. We conclude that the dog offers useful in vitro and in vivo models in which to investigate mast cell behaviour, and that its use should be considered when undertaking studies aimed either at elucidating the role of mast cells in health and disease, or at prescreening novel therapies prior to entry into man.
A 63-year-old man with a recurrent right-sided pleural effusion: Figure 1
Authors: John P Corcoran, Emma L Culver, Ioannis Psallidas, Robert J Hallifax, Susan J Davies, Adrian C Bateman, Eleanor Barnes, Najib M Rahman
Journal: Thorax (2015)

JPC : A 63-year-old Caucasian man was seen in clinic having been referred by his general practitioner with a 10 -week history of progressive exertional dyspnoea, associated with dry cough and retrosternal discomfort over the preceding fortnight. There was no history of fever, weight loss, anorexia, haemoptysis, dysphagia or other localising systemic symptoms. His past medical history included psoriatic arthropathy, atrial fibrillation, hypertension and gastro-oesophageal reflux; of note, there was no recent history of palpitations or worsening peripheral oedema, while his joint disease remained quiescent. Current medications (all long-standing) included methotrexate, omeprazole, bisoprolol, aspirin, ramipril and simvastatin. He was a lifelong non-smoker and retired solicitor with no occupational risk factors for lung disease.

On examination he was afebrile with no palpable lymphadenopathy or clubbing. Cardiovascular examination demonstrated rate-controlled atrial fibrillation only; abdominal examination was normal. Respiratory examination revealed dull percussion note and reduced breath sounds at the right lung base, with normal resting oxygen saturations. Chest radiograph and thoracic ultrasound confirmed the presence of a large right-sided pleural effusion. Routine bloods including full blood count, clotting studies, renal function, liver function and serum calcium were unremarkable. I performed a diagnostic and therapeutic pleural aspiration, draining 1500 mL of straw-coloured fluid with no complications. Laboratory analysis showed the effusion to be an exudate (protein 46 g/L, lactate dehydrogenase (LDH) 961 IU/L, glucose 0.4 mmol/L); pleural fluid culture and cytology (including flow cytometry) were negative.

NMR : The presence of a cytology-negative exudative pleural effusion of unknown aetiology in a previously well individual requires urgent further investigation. The low pleural fluid glucose and high LDH may imply infection, although these findings are non-specific and can also be seen in the context of chronic inflammation or malignancy; furthermore, the clinical history and negative culture go against an infective cause. The presence of an inflammatory arthropathy may prompt consideration …
A pragmatic assessment of the placement of oxygen when given for exercise induced dyspnoea
Authors: J W W Killen
Journal: Thorax (2000)

<h3>BACKGROUND</h3> It is uncertain whether patients with chronic obstructive pulmonary disease (COPD) given oxygen for symptom relief should be advised to use it before or after exertion. <h3>METHODS</h3> Eighteen patients with smoking related COPD who desaturated on exercise were given oxygen or air from a cylinder in a single blind manner and in an order determined by Latin square randomisation, before and after ascending stairs. The time of ascent, desaturation, and dyspnoea associated with the ascent was compared across the treatment groups. <h3>RESULTS</h3> Oxygen given before or after the ascent reduced maximal dyspnoea from 49.1 mm (95% CI 35.5 to 62.7) to 41.7 mm (95% CI 34.3 to 49.1) of a 100 mm visual analogue scale, reduced desaturation (oxygen before 4.9% (95% CI 3.6 to 6.2), oxygen after 6.4% (5.3 to 7.5), air before and after 8.2% (6.7 to 9.7%)), but did not affect time of ascent (air before: 5.1 s (95% CI 3.4 to 6.9) reduction from training ascent; oxygen before: 6.1 s (95% CI 2.9 to 9.2) reduction). <h3>CONCLUSIONS</h3> Oxygen prescribed for symptomatic relief of dyspnoea benefits selected patients with COPD, but it seems not to matter whether it is taken before or after exertion.
Hemodynamic regulation of myosin heavy chain gene expression. Studies in the transplanted rat heart.
Authors: I Klein, K Ojamaa, A M Samarel, R Welikson, C Hong
Journal: Journal of Clinical Investigation (1992)

Cardiac work is a major determinant of heart size and growth. Heterotopic cardiac isografts are hemodynamically unloaded and undergo atrophy. To determine the molecular changes that occur as a result of hemodynamic unloading, we have studied the rate of synthesis of total cardiac proteins and myosin heavy chain (MHC) and the expression of the myosin heavy chain gene as reflected in the messenger RNA levels for alpha- and beta-MHC isoforms. 72 h after transplantation there is a significant decrease in left ventricular size accompanied by a 27% decrease in the rate of total cardiac protein synthesis and a 53% decrease in the rate of myosin heavy chain synthesis. In contrast to isografts 14 d after transplantation which have a decrease in protein synthetic capacity, simultaneous measurements of 18S ribosomal RNA and myosin messenger RNA suggest that after 3 d the decrease in synthesis is due to a change in the efficiency of protein translation. While the working in situ heart expresses primarily alpha-MHC mRNA (97%) hemodynamic unloading leads to a 43% decrease in alpha-MHC mRNA concentration and the de novo expression of the beta-MHC mRNA. Total MHC mRNA (alpha plus beta) concentration analyzed by a quantitative S1 nuclease protection assay was similar in the two groups of hearts. Thus, in association with hemodynamic unloading there are changes in cardiac myosin heavy chain content as a result of both gene transcription and protein translation mechanisms.
Acute kidney injury and in-hospital mortality in critically ill patients with cirrhosis: a cohort study
Authors: José António Lopes, Maria João Melo, Ana Cortesão Costa, Mário Raimundo, Paula Alexandrino, António Gomes da Costa, José Velosa
Journal: Gut (2011)

<h3>Abstract</h3> Vessel co-option in colorectal cancer liver metastases (CRCLM) has been recognized as one of the mechanistic pathways that contribute to resistance against anti-angiogenic therapy. In vessel co-opted CRCLM lesions, the cancer cells are highly motile that move toward and along the pre-existing sinusoidal vessels and hijack them to gain access to nutrient. The movement of cancer cells is accompanied by replacement of the hepatocytes. However, the molecular mechanisms by which this replacement occurs are unclear yet. To examine the involvement of apoptosis in hepatocytes replacement by cancer cells in co-opted lesions, we conducted immunohistochemical staining for chemonaïve CRCLM specimens using pro-apoptotic markers antibody, such as cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase-1 (PARP-1). The results suggested overexpression of pro-apoptotic markers in liver parenchyma of co-opted lesions compared to angiogenic lesions, specifically the hepatocytes that are in close proximity to the cancer cells. Importantly, co-culturing hepatocytes with colorectal cancer cells induced overexpression of pro-apoptotic markers in the hepatocytes. Altogether, these results propose that cancer cells could exploit apoptosis to replace the hepatocytes and establish vessel co-option in CRCLM.
Ganglion Cell Loss in Relation to Visual Disability in Multiple Sclerosis
Authors: Scott D. Walter, Hiroshi Ishikawa, Kristin M. Galetta, Reiko E. Sakai, Daniel J. Feller, Sam B. Henderson, James A. Wilson, Maureen G. Maguire, Steven L. Galetta, Elliot Frohman, Peter A. Calabresi, Joel S. Schuman, Laura J. Balcer
Journal: Ophthalmology (2012)
Biologic and Immunologic Therapies for Ovarian Cancer
Authors: Jonathan S Berek, Birgit C Schultes, Christopher F Nicodemus
Journal: Journal of Clinical Oncology (2003)

Biologic therapy of ovarian cancer has been conducted using nonspecific biologic response modifiers, cytokines, monoclonal antibodies (MAbs), vaccines, and gene therapy. Antibodies directed toward her2/neu have also been studied. Phase I and II gene therapy trials using adenoviral vectors containing a wild-type or modified p53 have shown that the treatment is well tolerated. Phase II and III trials are ongoing with MAbs directed against CA-125 (MAb B43.13) and an antibody directed against HMFG1 (anti-HMFG1-yttrium-90-labeled antibody). The trials have shown that these agents are well tolerated and that immunologic responses occur, although the ultimate clinical value of these agents remains to be determined. Prolonged survival after MAb B43.13 treatment has been correlated with changes in several immune parameters, including human antimurine antibody, Ab2, anti-CA-125 antibody development, and induced T-cell immunity. Clinical trials using a MAb directed toward the encoded products of her2/neu have shown minimal activity against ovarian cancer in a phase I and II trial conducted by the Gynecologic Oncology Group. Cytokine therapies have been administered systemically and intraperitoneally. Intracavitary interferon alfa, interferon gamma, and interleukin-2 alone or in combination with cytotoxic therapy in phase I and II trials demonstrated intraperitoneal lymphoid cell stimulation and produced antitumor responses. A randomized trial of chemotherapy with or without interferon gamma in primary treatment produced a response and a progression-free survival advantage in the arm that incorporated the interferon gamma, without a statistically significant benefit in overall survival. A phase III study of interferon gamma in combination with first-line chemotherapy is currently ongoing.
Routine Use of a Small Digital Computer in the Clinical Laboratory
Authors: G. Phillip Hicks
Journal: JAMA (1966)

It is common for clinical laboratories to experience an increase in demand for their services out of proportion to the increase in the number of patients served. Since this increased reliance upon laboratory studies for diagnosis and follow-up care is based, at least in part, upon growth of knowledge of disease mechanisms, it is likely that this trend will continue. Efforts to cope with this expanding work load by introducing automatic analytical equipment have been only partly successful. There remain, not substantially affected by automation, an increasing number and variety of manually performed tests and the formidable task of processing the output of the automatic instruments. The use of digital computers has been proposed as a solution to this problem and several applications have been described.<sup>1-6</sup>These systems have involved largely the handling of data once thay have been put into computer-processable form. Relatively little attention has been given
Value of theophylline treatment in patients handicapped by chronic obstructive lung disease.
Authors: S E McKay, C A Howie, A H Thomson, B Whiting, G J Addis
Journal: Thorax (1993)

BACKGROUND: It is still not certain whether it is worth using theophylline in addition to inhaled bronchodilators and corticosteroids to treat obstructive airways disease. This trial was designed to test whether the addition of prescribed theophylline in doses sufficient for sustained optimal steady state plasma concentrations would produce any detectable additional advantage in spirometric or functional variables in these handicapped patients. METHODS: A randomised, double blind, placebo controlled, crossover study of added theophylline treatment was aimed at steady state plasma concentrations of 10 and 17 mg/l, the dose being calculated individually by Bayesian parameter estimation and maintained for six weeks along with the patient9s previously prescribed bronchodilators and steroids. Of 20 patients sequentially recruited, 15 provided data that could be analysed. All had chronic obstructive lung disease with a mean forced expiratory volume in the first second (FEV1) up to about 30% of the predicted value and gave no history of being treated with theophylline. The protocol included spirometry, whole body plethysmography, and treadmill exercise. Measurements also included steady state plasma theophylline concentrations and trapped gas volume. Quality of life was assessed by an established questionnaire method covering breathlessness in everyday activities, fatigue, emotional function, and control over the disease. RESULTS: Both target plasma concentrations were achieved. Improvements in peak flow (PEF; mean 20%), trapped gas volumes (38%), two stage vital capacity (15%), distances walked (48%), breathlessness in everyday activities (32%), and fatigue (18%) were found at the higher plasma concentration only. FEV1, forced vital capacity (FVC), emotional function, and control did not change. CONCLUSION: Theophylline treatment with sustained steady state concentrations about 17 mg/l provides worthwhile objective and subjective further benefits for patients handicapped by chronic obstructive lung disease when it is added to bronchodilators and corticosteroids.
Major histocompatibility complex restriction fragment length polymorphisms define three diabetogenic haplotypes in BB and BBN rats.
Authors: J B Buse, R Rifai-Haddad, S Lees, H Taniguchi, D Chaplin, E M Milford, J G Seidman, G S Eisenbarth, R A Jackson
Journal: The Journal of Experimental Medicine (1985)

Class I and II major histocompatibility complex (MHC) probes can be used to subdivide diabetes-prone BB rats and their BBN control strain, coderived from the same outbred colony by selection against diabetes. Class II probes (A-alpha in particular) distinguish four restriction fragment length polymorphisms (RFLP), termed 1a, 1b, 2a, and 2b, in the BBN population, only one of which (2a) is found in BB rats. The degree of class II RFLP in the population studied is RT1.B-alpha greater than or equal to RT1.B-beta greater than RT1.D-alpha greater than or equal to RT1.D-beta, suggesting that intra-class II region dynamics may be different in rats compared with mice. A class I probe (S16) absolutely distinguished BB from BBN rats, since all BB rats exhibit an RFLP pattern termed 2a0, while 2a BBN rats can be subdivided into 2a1 and 2a2 forms. Serologic evaluation has shown that 2a0, 2a1, and 2a2 rats express RT1.AuBu, 1a rats express RT1.AaDa, and 1b rats express neither RT1a nor RT1u at the loci tested. A breeding study was carried out to determine the diabetogenicity of the MHC-defined RFLP's. As expected, the BB-derived 2a0 is diabetogenic. The BBN-derived 2a1 and 2a2 RFLPs are also diabetogenic, while 1a and 1b rats do not carry MHC-linked diabetogenic genes. The MHC-linked diabetes gene acts in a functionally recessive manner, since there is a 10-fold higher incidence in homozygotes than in heterozygotes. Analysis of the RFLP patterns leads us to hypothesize that the 2a1 RFLP results from a crossover between 1a and 2a0 MHCs and that the diabetogenic MHC-linked gene is on the class II side of Qa and T1. The availability of three diabetogenic MHC haplotypes should help localize the MHC-linked diabetogenic gene of rats.
P60 Simple measures to improve TB control: applying the cohort review process in London
Authors: J. White, C. Anderson, S. Dart, S. Tamne, J. deKoningh, S. Hemming, S. Anderson, I. Abubakar, M. Lipman
Journal: Thorax (2011)

Despite much recent effort, there has been little change in national rates of tuberculosis (TB). Outside of the UK, the brief, structured review of the management, contact investigation and outcome of each TB case during their treatment (cohort review, CR) has improved TB control. North Central London (NCL) TB Service has piloted this approach. To date, 525 subjects with active TB have been discussed at four cohort reviews. Each “cohort” of patients were reviewed 6–9 months from start of treatment. A single case is usually reviewed within 3 min. Here we compare key outcomes relating to case management and contact tracing between an NCL TB population notified and treated prior to CR (Quarter 3 2009, n=158) and following CR implementation (Quarter 3, 2010, 1 year from start, n=125). Treatment completion rates rose (82%–90%). The proportion of cases lost to follow-up reduced (2.5%–0%). The proportion of smear positive pulmonary cases with at least one risk factor on Directly Observed Therapy increased from 42% to 67%. Uptake of HIV testing rose (71%–89%). The proportion of pulmonary TB cases with at least 1 and &gt;5 contacts identified both increased (64%–84% and 50%–67%, respectively). In conclusion, within a short space of time cohort review has led to an improved index case management and contact tracing process in our service. It improves accountability, enhances patient management and facilitates staff education. Accurate, comprehensive and prompt data underpin this success. If this is sustained, we believe that cohort review will result in improved patient outcomes. It provides, also, an excellent structure within which advances such as the National Strain Typing project may be introduced to achieve maximal clinical impact.
GATA-2 Plays Two Functionally Distinct Roles during the Ontogeny of Hematopoietic Stem Cells
Authors: Kam-Wing Ling, Katrin Ottersbach, Jan Piet van Hamburg, Aneta Oziemlak, Fong-Ying Tsai, Stuart H. Orkin, Rob Ploemacher, Rudi W. Hendriks, Elaine Dzierzak
Journal: The Journal of Experimental Medicine (2004)

GATA-2 is an essential transcription factor in the hematopoietic system that is expressed in hematopoietic stem cells (HSCs) and progenitors. Complete deficiency of GATA-2 in the mouse leads to severe anemia and embryonic lethality. The role of GATA-2 and dosage effects of this transcription factor in HSC development within the embryo and adult are largely unexplored. Here we examined the effects of GATA-2 gene dosage on the generation and expansion of HSCs in several hematopoietic sites throughout mouse development. We show that a haploid dose of GATA-2 severely reduces production and expansion of HSCs specifically in the aorta-gonad-mesonephros region (which autonomously generates the first HSCs), whereas quantitative reduction of HSCs is minimal or unchanged in yolk sac, fetal liver, and adult bone marrow. However, HSCs in all these ontogenically distinct anatomical sites are qualitatively defective in serial or competitive transplantation assays. Also, cytotoxic drug-induced regeneration studies show a clear GATA-2 dose-related proliferation defect in adult bone marrow. Thus, GATA-2 plays at least two functionally distinct roles during ontogeny of HSCs: the production and expansion of HSCs in the aorta-gonad-mesonephros and the proliferation of HSCs in the adult bone marrow.
Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.
Authors: M Detmar, L F Brown, K P Claffey, K T Yeo, O Kocher, R W Jackman, B Berse, H F Dvorak
Journal: The Journal of Experimental Medicine (1994)

Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vascular endothelial growth factor), a selective endothelial cell mitogen that enhances microvascular permeability. Moreover, two VPF receptors, kdr and flt-1, are overexpressed by papillary dermal microvascular endothelial cells. Transforming growth factor alpha (TGF-alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene expression by cultured epidermal keratinocytes. VPF secreted by TGF-alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperpermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.