tbuckley/cabot-search huggingface dataset:
Common Foot Ailments
Authors: W. S. Creer
Journal: BMJ (1938)

Abnormalities and deformities of the feet causing pain and disabilityare so exceedingly common that the diffi- culty is to choose conditions which can be described and discussed with profit within a reasonable space.I am told that the average medical practitioner is ignorant of them because there is no literature in which he can read about them.This is not strictly true, though one must admit that the textbooks dismiss the subject with very few words and that only the specialist is likely to read the journals or buy the books in which full descriptions are given.It is in the hope that help can be given that I have dared to produce this resume.The medical profession is privileged to see the private life of the public, to enjoy confidences not given to any other, and is at times burdened with the responsibility of making or marring a life.The orthopaedic surgeon's responsibility is, very often, to restore an injured workman to full earning capacity or to relieve the foot troubles of those whose life is, to say the least, made a burden because of pain.This problem of pain, so frequently glossed over or forgotten, is a very real one; and because there is a wide- spread belief among the public that surgeons are " too fond of the knife" there is a great deal of hesitation in seeking aid.Too often after assuring the patient that some simple form of non-surgical treatment will give relief one hears the sigh, " I wish I had known that twenty years ago! " For twenty years afraid to seek help!What this aid could have amounted to is revealed by a consideration of some common foot ailments and their treatment without recourse to surgery.No better idea of the prevalence and ratio of some of these conditions can be obtained than by analysing the figLures for the orthopaedic clinics of two foot hospitals.
Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition
Authors: Oliver Weigert, Andrew A. Lane, Liat Bird, Nadja Kopp, Bjoern Chapuy, Diederik van Bodegom, Angela V. Toms, Sachie Marubayashi, Amanda L. Christie, Michael McKeown, Ronald M. Paranal, James E. Bradner, Akinori Yoda, Christoph Gaul, Eric Vangrevelinghe, Vincent Romanet, Masato Murakami, Ralph Tiedt, Nicolas Ebel, Emeline Evrot, Alain De Pover, Catherine H. Régnier, Dirk Erdmann, Francesco Hofmann, Michael J. Eck, Stephen E. Sallan, Ross L. Levine, Andrew L. Kung, Fabienne Baffert, Thomas Radimerski, David M. Weinstock
Journal: The Journal of Experimental Medicine (2012)

Enzymatic inhibitors of Janus kinase 2 (JAK2) are in clinical development for the treatment of myeloproliferative neoplasms (MPNs), B cell acute lymphoblastic leukemia (B-ALL) with rearrangements of the cytokine receptor subunit cytokine receptor–like factor 2 (CRLF2), and other tumors with constitutive JAK2 signaling. In this study, we identify G935R, Y931C, and E864K mutations within the JAK2 kinase domain that confer resistance across a panel of JAK inhibitors, whether present in cis with JAK2 V617F (observed in MPNs) or JAK2 R683G (observed in B-ALL). G935R, Y931C, and E864K do not reduce the sensitivity of JAK2-dependent cells to inhibitors of heat shock protein 90 (HSP90), which promote the degradation of both wild-type and mutant JAK2. HSP90 inhibitors were 100–1,000-fold more potent against CRLF2-rearranged B-ALL cells, which correlated with JAK2 degradation and more extensive blockade of JAK2/STAT5, MAP kinase, and AKT signaling. In addition, the HSP90 inhibitor AUY922 prolonged survival of mice xenografted with primary human CRLF2-rearranged B-ALL further than an enzymatic JAK2 inhibitor. Thus, HSP90 is a promising therapeutic target in JAK2-driven cancers, including those with genetic resistance to JAK enzymatic inhibitors.
Differential Effects of Insulin- and Proinsulin-Induced Hypoglycemia on Pituitary Hormone and Catecholamine Secretion
Authors: Timothy C Williams, Michael Berelowitz, Michael A Berk, Lawrence A Frohman
Journal: Diabetes Care (1987)

The effects of insulin- and proinsulin-induced hypoglycemia on pituitary hormone and catecholamine secretion were compared in normal men to search for possible hypothalamic or pituitary inhibitory effects of proinsulin on glucocounterregulatory responses. When subjects received 0.1 U/kg i. v. human insulin and 25–38 μg/kg i.v. human proinsulin on separate occasions, plasma glucose decreased more rapidly after insulin, and the nadir was slightly lower, but integrated hypoglycemic responses were similar. Cortisol, growth hormone (GH), prolactin, epinephrine, and norepinephrine responses occurred more rapidly after insulin than after proinsulin. Peak and integrated cortisol, GH, and catecholamine responses to insulin and proinsulin were similar, but those of prolactin were reduced after proinsulin when compared with insulin by 42% (P &amp;lt; .01) and 34% (P &amp;lt; .05), respectively. When euglycemia was maintained by a variable glucose infusion rate after the injection of insulin and proinsulin, no differences were observed in plasma levels of any of the hormones. The intravenous injection of a dose of proinsulin (6 μg/kg), which did not produce hypoglycemia but was the molar equivalent of insulin used in the first protocol, failed to modify the GH or prolactin responses to a combined injection of GH-releasing hormone (1 μg/kg) and thyrotropin-releasing hormone (500 (xg). Our results indicate that the onset of pituitary hormone and catecholamine responses to hypoglycemia are related to the rate of plasma glucose decline, with the slower responses to proinsulin reflecting a more gradual onset of hypoglycemia. The magnitude of the cortisol, GH, and catecholamine responses, however, was comparable with proinsulin- and insulin-induced hypoglycemia. In contrast, the reduced peak and integrated prolactin responses to proinsulin imply that proinsulin-induced hypoglycemia is a submaximal stimulus for prolactin secretion or that proinsulin inhibits prolactin secretion at the hypothalamic level.
S12 Experience with Intrapleural Tissue Plasminogen Activator and DNase in the Treatment of Pleural Infection: Abstract S12 Table 1
Authors: NI Pitman, RA McCartney, C O’Dowd, KG Blyth, B Choo-Kang, MK Johnson
Journal: Thorax (2012)

<h3>Introduction</h3> Intrapleural infection remains a significant cause of morbidity and mortality. In many patients medical management with chest tube drainage and antibiotics fails and surgical intervention is required. The MIST2 trial reported improved resolution following intrapleural treatment with combined tissue plasminogen activator and DNase (tPA/DNase). <h3>Aims</h3> To study the outcomes in patients with pleural infection treated with tPA/DNase over a one year period in a 1,109 bed city centre hospital. <h3>Methods</h3> A prospective audit was undertaken of all patients with pleural infection treated with intrapleural tPA/DNase. The decision to initiate therapy was at the discretion of the treating team. The main outcomes were changes in chest drain output and CXR opacification, complications, and surgical intervention. The area of pleural opacity was calculated using the method described by the MIST2 group. <h3>Results</h3> Ten patients were treated over a one year period, all of whom had clinical features of infection and yielded frank pus or pleural fluid with a pH below 7.2. Treatment with tPA/DNase was not initiated as a first line therapy in any patient. All were initially managed with chest tube drainage and antibiotics and the decision to initiate tPA/DNase was due to subsequent poor or absent drain output combined with evidence of persistent pleural fluid. Changes in pleural fluid output and pleural opacification on CXR following treatment are shown in Table 1. In one patient treatment was discontinued after 1 dose due to a non-functioning drain and in one patient treatment was discontinued after the fifth dose due to heavy blood staining of the pleural fluid. There were no other treatment related complications. Only one patient required cardiothoracic intervention and all patients were discharged home. <h3>Conclusions</h3> In keeping with the MIST2 trial, these data suggest that intrapleural tPA/DNase can safely be used to treat pleural infection. In this selected group of patients that failed to respond to conventional medical management tPA/DNase treatment led to further fluid drainage with an associated reduction in pleural opacification and a low requirement for cardiothoracic intervention.
The Retreat From Advanced Care Planning
Authors: Mary E Tinetti
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
NUCLEAR AND MITOCHONDRIAL COMPARTMENTATION OF OXIDATIVE STRESS AND REDOX SIGNALING
Authors: Jason M. Hansen, Young-Mi Go, Dean P. Jones
Journal: The Annual Review of Pharmacology and Toxicology (2005)

New methods to measure thiol oxidation show that redox compartmentation functions as a mechanism for specificity in redox signaling and oxidative stress. Redox Western analysis and redox-sensitive green fluorescent proteins provide means to quantify thiol/disulfide redox changes in specific subcellular compartments. Analyses using these techniques show that the relative redox states from most reducing to most oxidizing are mitochondria > nuclei > cytoplasm > endoplasmic reticulum > extracellular space. Mitochondrial thiols are an important target of oxidant-induced apoptosis and necrosis and are especially vulnerable to oxidation because of the relatively alkaline pH. Maintenance of a relatively reduced nuclear redox state is critical for transcription factor binding in transcriptional activation in response to oxidative stress. The new methods are applicable to a broad range of experimental systems and their use will provide improved understanding of the pharmacologic and toxicologic actions of drugs and toxicants.
Dose-Finding Study of the Multitargeted Tyrosine Kinase Inhibitor SU6668 in Patients with Advanced Malignancies
Authors: Bart C. Kuenen, Giuseppe Giaccone, Rita Ruijter, Astrid Kok, Casper Schalkwijk, Klaas Hoekman, Herbert M. Pinedo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: SU6668 is a tyrosine kinase inhibitor which targets platelet-derived growth factor receptor-β, fibroblast growth factor receptor-1, vascular endothelial growth factor receptor-2, and KIT. We did a phase I study to define the maximum tolerated dose and to assess the pharmacokinetics of SU6668 administered orally thrice daily with food. Patients and Methods: Patients with histologically proven, advanced, and progressive solid tumors were included at a starting dose level of 400 mg/m2 thrice daily. The early onset of dose-limiting toxicities (DLT) required dose reductions to 100 and 200 mg/m2 thrice daily. Pharmacokinetics was done on days 1, 28, and 56. Results: Sixteen patients were included. Two of the first three patients developed DLTs, which consisted of grade 4 fatigue and grade 3 serositis-like pains. Six patients at dose level 100 mg/m2 thrice daily experienced no DLT. At dose level 200 mg/m2 thrice daily, two out of seven patients experienced DLTs consisting of grade 3 abdominal pain, grade 4 anorexia and grade 3 nausea/vomiting. Increasing doses resulted in a disproportional increase in area under the curve and Cmax (peak plasma concentration). Both variables, however, decreased significantly on days 28 and 56 compared with day 1 (P &amp;lt; 0.05). No objective responses were observed. Acute phase response, probably mediated by interleukin-6, was observed in serial blood samples. Conclusions: The maximum tolerated dose of SU6668 given orally, thrice daily under fed conditions, is 100 mg/m2. Because of the low plasma levels reached at this dose level, the efficacy of SU6668 as a single agent is not to be expected.
Effectiveness of hip protectors for preventing hip fractures in elderly people: systematic review
Authors: Martyn J Parker, William J Gillespie, Lesley D Gillespie
Journal: BMJ (2006)

To present the updated results of systematic review of the current evidence for the effectiveness of hip protectors from reports of completed randomised trials, and to explore the evolution of that evidence.Systematic review with meta-analysis.Cochrane Bone, Joint, and Muscle Trauma Group trials register (January 2005), Cochrane central register of controlled trials (Cochrane Library Issue 1, 2005), Medline (1966 to January 2005), Embase (1988 to January 2005), and CINAHL (1982 to December 2004). Other databases and reference lists of relevant articles were searched and some trialists were contacted.Randomised or quasirandomised controlled trials reporting the incidence of hip fractures, pelvic fractures, and other fractures in elderly people offered hip protectors compared with a control group that was not.Outcomes for fracture were available from 14 randomised and quasirandomised trials. Pooling of data from 11 trials carried out in nursing or residential care settings, including six cluster randomised studies, showed evidence of a marginally statistically significant reduction in incidence of hip fracture (relative risk 0.77, 95% confidence interval 0.62 to 0.97). Pooling of data from three individually randomised trials of 5135 community dwelling participants showed no reduction in hip fracture incidence with provision of hip protectors (1.16, 0.85 to 1.59). No evidence was found of any significant effect of hip protectors on incidence of pelvic or other fractures. No important adverse effects of hip protectors were reported, but compliance, particularly in the long term, was poor.On the basis of early reports of randomised trials, hip protectors were advocated. Accumulating evidence indicates that hip protectors are an ineffective intervention for those living at home and that their effectiveness in an institutional setting is uncertain.
Necrotising aspergillosis complicating fulminating viral pneumonia.
Authors: A G Jariwalla, A P Smith, G Melville-Jones
Journal: Thorax (1980)

Post-influenzal bronchopneumonia is commonly bacterial, usually pnuemococcal or staphylococcal, though in the 1957 pandemic fatal cases of pure viral pneumonia were recorded.'We report a case of necrotising or invasive aspergillosis complicating a fulminating viral pneumonia in a 14-year-old girl. Case reportAfter a holiday in Devon in September 1977, a previously fit 14-year-old schoolgirl developed headaches, myalgia, sore throat, and fever.She was given a seven-day course of tetracycline, followed by four days on magnapen, without any improvement.Over the 24 hours before admission to hospital she developed progressive dyspnoea and severe respiratory distress.On examination she was febrile (39-8°C), cyanosed, confused, and had bilateral coarse inspiratory and expiratory lung crackles.She was well perfused and normotensive.Chest radiograph showed extensive bilateral confluent nodular infiltration.Haemoglobin was 9 9 g/dl, and white cell count 22 1 x 109 per litre -96% neutrophils, 3 % lymphocytes, and 1 % monocytes.Blood film was normocytic normochromic.Erythrocyte sedimentation rate was 86 in one hour (Westergren).Platelet count was 440 000mm3, reticulocytes less than I %.Arterial blood gases showed Pao2 8-1 kPa Paco2 7-6 kPa on roomn air.Parainfluenzal complement fixation test was 1: 32 on two occasions.Bronchial secretions, although purulent, did not reveal respiratory pathogens or acid-fast bacilli.Fluorescent antibody test against Legionella pneumophila was negative.The following tests were normal: bone marrow histology, electrolytes, serum and urine osmola- lity, electrocardiograph, Coombs' test, Toxoplasma dye test, serial blood cultures, cold agglutinins, histology of lung aspirate obtained via bronchoscopy, liver function tests, Paul Bunnell, immunoglobulins, protein electrophoresis, urine for acid-fast bacilli and pathogens, and blood sugar.Various other investigations for dis- seminated neoplasm, collagen diseases, pulmonary alveolar proteinosis, and disseminated intravascular coagulation, were negative.Precipitating antibodies to Aspergillus fumigatus, reported after the patients death, were strongly positive.The patient was ventilated with intermittent positive pressure and given ampicillin, cloxacillin, tetracycline, gentamicin, and amantadine.Methyl prednisolone (4g daily for eight days) was also given.She
Access to Primary Care in England
Authors: Thomas E. Cowling, Matthew J. Harris, Azeem Majeed
Journal: JAMA Internal Medicine (2015)

after levothyroxine therapy initiation would have had to have been unrecognized by health professionals over several years and therefore is likely to represent only a small number of individuals.Jolobe is also right to draw attention to the risk of overreplacement with levothyroxine in precipitating a transition from paroxysmal to persistent atrial fibrillation, which would certainly outweigh the benefits of replacement therapy, especially when the hypothyroidism is subclinical and the patient is elderly.
Where is the classic interference theory for sleep and memory?
Authors: Anton Coenen
Journal: Behavioral and Brain Sciences (2005)

Walker's target article proposes a refinement of the well known two-stage model of memory formation to explain the positive effects of sleep on consolidation. After a first stage in which a labile memory representation is formed, a further stabilisation of the memory trace takes place in the second stage, which is dependent on (REM) sleep. Walker has refined the latter stage into a stage in which a consolidation-based enhancement occurs. It is not completely clear what consolidation-based enhancement implies and how it can be dissociated from a stage for memory-stabilisation. A more serious consideration, however, is whether a second stage in memory consolidation that is solely dependent on sleep, is really necessary. The classical, passive, interference theory is able to explain adequately the findings related to the effects of sleep and memory, and can lead perhaps better to an understanding of the highly variable data in this field.
Identification of Hypoxia-Regulated Proteins in Head and Neck Cancer by Proteomic and Tissue Array Profiling
Authors: Yijun Chen, Gongyi Shi, Wei Xia, Christina Kong, Shuchun Zhao, Allison F. Gaw, Eunice Y. Chen, George P. Yang, Amato J. Giaccia, Quynh-Thu Le, Albert C. Koong
Journal: Cancer Research (2004)

Abstract Hypoxia within solid tumors decreases therapeutic efficacy, and identification of hypoxia markers may influence the choice of therapeutic modality. Here, we used a proteomic approach to identify hypoxia-regulated proteins and validated their use as endogenous indicators of tumor hypoxia. Using two-dimensional gel electrophoresis and PowerBlot (antibody-based array), we identified a group of 20 proteins that are increased ≥1.5-fold during hypoxia. The majority of these proteins such as IκB kinase β (IKKβ), MKK3b, highly expressed in cancer (HEC), density-regulated protein 1, P150glued, nuclear transport factor 2, binder of ARL 2, Paxillin, and transcription termination factor I have not been previously reported to be hypoxia inducible. The increase in these proteins under hypoxia was mediated through posttranscriptional mechanisms. We additionally characterized the role of IKKβ, a regulator of the nuclear factor-κB transcription factor, during hypoxia. We demonstrated that IKKβ mediates cell survival during hypoxia and is induced in a variety of squamous cell carcinoma cell lines. Furthermore, we showed that IKKβ expression from tumor specimens correlated with tumor oxygenation in patients with head and neck squamous cell carcinomas. These data suggest that IKKβ is a novel endogenous marker of tumor hypoxia and may represent a new target for anticancer therapy.
Reversal of the Malignant Phenotype of Cervical Cancer CaSki Cells through Adeno-Associated Virus–Mediated Delivery of HPV16 E7 Antisense RNA
Authors: Sufang Wu, Li Meng, Shixuan Wang, Wei Wang, Ling Xi, Xun Tian, Gang Chen, Ying Wu, Jianfeng Zhou, Gang Xu, Yunping Lu, Ding Ma
Journal: Clinical Cancer Research (2006)

Abstract Human papillomavirus (HPV) infection is the most important risk factor for the development of cervical cancer. The oncogene E7 from high-risk HPV strains has the ability to immortalize epithelial cells and increase cellular transformation in culture. In this study, we explored the possibility of preventing cervical cancer growth by inhibiting HPV16 E7 expression through gene transfer of an antisense construct. A recombinant adeno-associated virus (rAAV) vector was chosen for the transfer, based on its transfection efficiency, in vivo stability, and lack of detectable pathology. In vitro transfer of an rAAV vector expressing antisense HPV16 E7 (AAV-HPV16E7AS) inhibited cell proliferation, induced apoptosis, reduced cell migration, and restrained in vivo proliferation of HPV16/HPV18–positive cervical cancer CaSki cells. These results indicate that down-regulation of HPV16 E7 with antisense RNA is beneficial in reducing the tumorigenicity of CaSki cells, and rAAV vectors ought to be a new efficient approach for delivering the expression of therapeutic genes.
Risperidone, haloperidol, and placebo in the treatment of aggressive challenging behaviour in patients with intellectual disability: a randomised controlled trial
Authors: Peter Tyrer, Patricia C Oliver-Africano, Zed Ahmed, Nick Bouras, Sherva Cooray, Shoumitro Deb, Declan Murphy, Monica Hare, Michael Meade, Ben Reece, Kofi Kramo, Sabyasachi Bhaumik, David Harley, Adrienne Regan, David Thomas, Bharti Rao, Bernard North, Joseph Eliahoo, Shamshad Karatela, Anju Soni, Mike Crawford
Journal: The Lancet (2008)
THE NATURE OF ANTIGEN-ANTIBODY COMPLEXES FORMED IN RABBITS DURING AN IMMUNE RESPONSE TO BOVINE SERUM ALBUMIN
Authors: William O. Weigle
Journal: The Journal of Experimental Medicine (1958)

The immune elimination of soluble BSA, following an intravenous injection, is accompanied by the appearance of circulating antigen-antibody complexes. The pattern of the appearance of circulating antigen-antibody complexes and the immune elimination of antigen probably depends on the amount of antigen injected, the rate of antibody synthesis, and perhaps, the quality of antibody produced. There is no relationship between the I* antigen-antibody complexes detected during the immune response in rabbits by ammonium sulfate precipitation and the material precipitated from immune sera as a result of treatment with alkali. Alkali-precipitable material present in the serum of rabbits at a time when I* antigen is also present contain at most only traces of the antigen.