tbuckley/cabot-search huggingface dataset:
THE EFFECT OF INFLAMMATORY REACTIONS ON TISSUE IMMUNITY
Authors: Franklin M. Hanger
Journal: The Journal of Experimental Medicine (1930)

1. Animals showing natural bacterial allergy to filtrates of B. lepisepticum survive infection by this organism more frequently than weak reactors. This increased resistance is manifested by better localization of infection. 2. Bacterial filtrates injected into skin 24 hours before infection exert a non-specific protection of that area against the organism, even in susceptible animals. The cells of this protected area seldom undergo necrosis when infected. 3. Severe injury of tissues either by chemicals or an antigen-antibody reaction produces a loss of local resistance even in immune animals. Mild injuries have the opposite effect. It is believed that in cases of severe injury, the affected areas undergo a segregation from the circulating antibodies. 4. When bacterial immune serum is injected with a protein antigen into the skin of a sensitized animal, a local alteration occurs in which substances necessary for the effective action of the immune serum are destroyed. 5. A protective action is restored to the altered immune serum by addition of complement to the lesion. 6. It is felt that allergy is not the chief mechanism in cellular resistance to infection, however data are advanced which suggest that allergy does exert local protection by acceleration of the immune processes and by rendering the cells locally refractory to further injury. 7. Chronic infection by a single strain of organism excites cellular reactivity to many strains of bacteria often unrelated biologically. Hence a non-specific mechanism for localizing infections throughout the body may be induced.
Public Health, Public Trust and Lobbying
Authors: Matthew K. Wynia
Journal: The American Journal of Bioethics (2007)

Each year, infection with Human Papillomavirus (HPV) leads to millions of abnormal Pap smears and thousands of cases of cervical cancer in the US. Throughout the developing world, where Pap smears are less common, HPV is a leading cause of cancer death among women. So when the international pharmaceutical giant Merck developed a vaccine that could prevent infection with several key strains of HPV, the public health community was anxious to celebrate a major advance. But then marketing and lobbying got in the way. Merck chose to pursue an aggressive lobbying campaign, trying to make its new vaccine mandatory for young girls. The campaign stoked public mistrust about how vaccines come to be mandated, and now it's not just Merck's public image that has taken a hit. The public health community has also been affected. What is the lesson to be learned from this story? Public health communication relies on public trust.
THE TREATMENT OF CHOREA BY LARGE DOSES OF QUININ.Read in the Section on Diseases of Children, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: W. A. N. DORLAND
Journal: JAMA (1893)

Of the various theories that have been advanced from time to time, in the effort to elucidate the etiology of chorea and to localize the affection; that is, to ascribe to the choreic movements either a cerebral, or a spinal, or a conjoined origin, that of a diminution or loss of spinal inhibition recently proposed by Prof. H. C. Wood in a contribution read before the Philadelphia Neurological Society and published in the<i>Journal of Nervous and Mental Diseases</i>for the month of April, may be accepted as pre-eminently a rational one; a theory that is based upon sound scientific investigation and deliberate ratiocination. We would invite a perusal of this very interesting paper, as giving in a more concise and intelligent manner than any resumè we could offer, the various steps that led up to the enunciation of the theory suggested. In the meanwhile, permit us to review briefly some
Real-time Imaging Assessment of Blood Flow, Temperature and Skin Color on Patients with Cold-induced Urticaria: Correlation with Histamine and Tryptase Release
Authors: H.D. Komarow, J. Meyer, A.M. Gorbach, W. Liu, N. Medic, M. Young, C. Nelson, S. Arceo, A. Desai, D.D. Metcalfe
Journal: Journal of Allergy and Clinical Immunology (2012)
Relationship between iron deposits and tissue damage in the synovium: an ultrastructural study.
Authors: C J Morris, D R Blake, A C Wainwright, M M Steven
Journal: Annals of the Rheumatic Diseases (1986)

A detailed ultrastructural study was made of the synovial iron deposits in cases of haemophilic synovitis (HS), pigmented villonodular synovitis (PVNS), rheumatoid arthritis (RA), osteoarthritis (OA), seronegative inflammatory arthritis (SNA), and in controls, to investigate the relationship between iron deposits and tissue damage. Iron was seen by electron microscopy in about 75% of synovial lining cells in HS and PVNS but only in about 25% of synovial cells from cases of RA and SNA. In cases of OA and in controls iron deposits were scarce. The iron was usually deposited within pleomorphic siderosomes and in HS was most common in type A synovial cells. In contrast, deposits in all other cases were more common in type B cells, which were frequently the predominant cell type, and siderosomes were smaller, more homogeneous, and were more common in deeper synovial tissue. Considerable tissue damage was noted in the vicinity of iron rich siderosomes in synovial A cells from cases of HS, but such deposits in B cells in the synovium from the other cases had relatively little effect. We discuss the possibility that such differences directly reflect the differing functions of type A and B synovial cells, and particularly their relative ability to produce metabolically active oxygen metabolites with tissue destructive potential in the presence of iron.
iWITNESS: A Retrospective Photographic Exhibition by Tom Stoddart
Authors: Sally Hargreaves
Journal: BMJ (2004)

Amounted text at the entrance to British photojournalist Tom Stoddart's latest exhibition states, “It is sad and unnecessary that any of these photos exist.” This powerful selection of Stoddart's often harrowing images—designed to mark the 40th anniversary of the Disasters Emergency Committee—is a personal view of someone who has observed the major humanitarian and health emergencies of the past decade at first hand; and is adamant that these events are not forgotten.

Stoddart, who has worked for international magazines such as Time and Newsweek , and British newspaper the Sunday Times , has captured those moments in which unutterable misery meets human courage, strength, and compassion. His pictures rarely need explanation—for example, the image of disoriented and frightened people helping each other as …
FOP-FGFR1 tyrosine kinase, the product of a t(6;8) translocation, induces a fatal myeloproliferative disease in mice
Authors: Géraldine Guasch, Bénédicte Delaval, Christine Arnoulet, Min-Jue Xie, Luc Xerri, Danielle Sainty, Daniel Birnbaum, Marie-Josèphe Pébusque
Journal: Blood (2003)
Abstract 3773: Absolute bioavailability of BRAF inhibitor GSK2118436: Use of a microtracer study in patients with cancer
Authors: Cathrine L. Denton, Stanley W. Carson, Graeme C. Young, Lauren E. Richards-Peterson, Jeffrey Botbyl, Royce A. Morrison, Samuel C. Blackman, Daniele Ouellet
Journal: Cancer Research (2012)

Abstract Background. Absolute bioavailability (BA) studies in oncology are logistically and technically challenging. Use of an intravenous (IV) microtracer offers an attractive alternative to conventional cross-over design studies. This method involves concomitant administration of a non-labeled oral therapeutic dose with a radiolabeled IV microtracer dose. Advantages include: 1) fewer subjects required as comparisons are within-subject and within-period, yielding reduced variability; 2) easier development of IV formulation for drugs with low solubility (microtracer doses are ≤ 100 μg); 3) radioactivity doses are low and do not require special handling (usually ≤ 270 nCi of 14C) and 4) negligible toxicity, as the contribution of the microtracer dose to overall exposure is typically &amp;lt; 0.5% of the oral dose. The approach required development of an ultra-sensitive assay using accelerator mass spectrometry (AMS) to determine pharmacokinetic (PK) parameters from IV dosing. The purpose of this study was to determine absolute BA for the BRAF inhibitor GSK2118436 in cancer patients. Methods. Patients with BRAF-mutant solid tumors were enrolled in an open-label, non-randomized study. Patients received a single oral dose of GSK2118436 (150 mg capsule) followed by a 15-min microtracer infusion (50 μg [14C] GSK2118436), started 1.75 h after the oral dose to coincide with oral Tmax. Plasma samples were collected at timed intervals up to 72 h post-oral dose. Total radioactivity and [14C] GSK2118436 were measured by AMS. Non-labeled GSK2118436 was measured by LC-MS/MS. PK parameters were calculated using standard non-compartmental methods. Results. Preliminary PK parameters were determined in 4 subjects (Table). Absolute BA, expressed as least squares mean (90% CI), was 84.2% (72.3-98.1). Conclusions. The absolute BA of oral GSK2118436 was high. This innovative IV microtracer study was an efficient and accurate way to determine absolute BA of GSK2118436 in patients with advanced cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3773. doi:1538-7445.AM2012-3773
IL-32 Expression in Chronic Rhinosinusitis
Authors: A. Kato, A. Keswani, R.T. Chustz, A. Peters, R. Chandra, R. Carter, L. Suh, J. Norton, K.E. Harris, D. Conley, L.C. Grammer, S. Kim, C.A. Dinarello, R.C. Kern, R.P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2010)
Strontium in Diet
Authors: F. J. Bryant, A. C. Chamberlain, G. S. Spicer, M. S. W. Webb
Journal: BMJ (1958)

Hormonal treatment with chorionic gonadotrophin is successful in bringing down more than 60% of a selected group of undescended testes.There is no evidence that chorionic gonadotrophin in moderate dosage can cause permanent damage to the seminiferous tubules.Orchidopexy is the treatment of choice when there is a mechanical defect or when chorionic gonadotrophin fails.Hormonal and surgical treatment should take place about the age of 9 or 10.Assessment of fertility in 24 patients with bilateral cryptorchidism reveals that 70% of them have a normal degree of fertility 10 years after treatment.
Maffucci’s Syndrome
Authors: M. Jermann, K. Eid, T. Pfammatter, R. Stahel
Journal: Circulation (2001)

A 30-year-old woman presented with painful hemangio- mas (Figure , A andB) and enchondromas (Figure ,C) in her arms, predominantly in the left hand.The hemangiomas had existed since childhood.They were slowly increasing in size, especially the girth of the left thumb.Multiple resections of enchondromas and transarterial carpal embolizations of the hemangiomas with polyvinyl alcohol particles had been performed during the previous 9 years.At the age of 22, the small finger of the left hand was removed.At the age of 25, a pathological fracture of the left humerus occurred due to an enchondroma.A contour reduction and partial excision of the most important nodules was performed.Serum levels of vascular endothelial growth factor and basic fibroblast growth factor were elevated 2-fold and 7-fold, respectively.The patient is in good clinical health and works part-time as a secretary.Maffucci's syndrome is a rare nonhereditary mesodermal dysplasia.It consists of multiple hemangiomas of the soft tissue and multiple enchondromas, which are most often found in the phalanges and long bones.The bone and vascular lesions exist at birth or occur during childhood and may be progressive.The syndrome can be associated with benign or malignant tumors (goiter, parathyroid adenoma, pituitary adenoma, hemangioendothelioma, adrenal tumor, ovarian tumor, chondrosarcoma, breast cancer, astrocytoma).
Slow release iodine preparation and wound healing: in vitro effects consistent with lack of in vivo toxicity in human chronic wounds
Authors: L.H. Zhou, W.K. Nahm, E. Badiavas, T. Yufit, V. Falanga
Journal: British Journal of Dermatology (2002)

Summary Background Antiseptic agents, particularly slow-release preparations, are increasingly being used in the management of chronic wounds. One such agent, cadexomer iodine, carries iodine (0·9% weight/weight) immobilized in beads of dextrin and epichlorhydrin and has been demonstrated to be highly effective in promoting healing of exudative wounds. However, there have been no studies directly assessing the potential lack of toxicity of cadexomer iodine on human cutaneous tissues. Objectives To determine if, within a certain concentration range, cadexomer iodine is non-toxic to human cells and cutaneous tissue and to assess histologically human chronic exudative wounds that are being treated with cadexomer iodine. Methods We examined the effects of varying concentrations of cadexomer iodine on the viability of human fibroblasts in culture (by trypan blue exclusion). The morphology, cellular proliferation capacity (measured by [3H]thymidine uptake), ability to produce α1(I) procollagen chain mRNA, and cell outgrowth from neonatal foreskin explants were also evaluated in human fibroblasts after incubation with various concentrations of cadexomer iodine. Moreover, biopsies of chronic exudative wounds concurrently treated with cadexomer iodine were stained with haematoxylin and eosin or a Gram stain and evaluated microscopically. Results At concentrations of up to 0·45%, cadexomer iodine was found to be non-toxic to fibroblasts in vitro; there were no changes in viability, morphology, cellular proliferation, ability to produce collagen, and cell outgrowth from explants. In vivo, skin biopsies of chronic exudative wounds being treated with cadexomer iodine demonstrated no evidence of cell necrosis, displayed re-epithelialization, and revealed bacteria within the cadexomer beads. Conclusions These studies demonstrate that cadexomer iodine has definite non-toxic concentration ranges for fibroblasts in vitro, which are consistent with a lack of cellular toxicity in human chronic exudative wounds treated with cadexomer iodine. Cadexomer iodine may also have the additional property of trapping microorganisms.
Permeation of polysucrose 15 000 across the human nasal mucosa <i>in vivo</i>
Authors: M. Andersson, L. Greiff, H. Öman, C. Svensson, P. Wollmer, C. G. A. Persson
Journal: Allergy (1997)

Studies of the nasal permeation of small molecules (&lt; 1000 Da) have yielded important information about the integrity of the human airway mucosa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15000 (approx. 14700 Da), to predict the mucosal permeation of inhalational allergens. PS 15000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nasal cavity of 12 healthy nonatopic subjects by employment of a nasal‐pool device. Permeation as determined by the 24‐h urine recovery of PS (micro‐ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009–0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007–2.260%) (P&lt;0.01). After oral intake of 750 mg of PS 15 000 (50 μg/ml; 15 ml), the 24‐h urinary recovery was 0.013% (range 0.004–0.023%). Our study thus demonstrates a measurable baseline permeation of PS 15 000, an elevated permeation rate in the presence of an epithelium‐damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15 000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens.
Screening for colorectal cancer in ulcerative colitis: dubious benefits and high costs.
Authors: S Gyde
Journal: Gut (1990)

Leading articleScreening for colorectal cancer in ulcerative colitis: dubious benefits and high costs The primary role of the medical profession is to diagnose and treat members of the population who identify themselves as being 'sick' in some way.In this situation 'patients' approach the doctors.It is only recently that doctors have involved themselves in 'screening' apparently healthy members of the population in order to diagnose disease at a presymptomatic stage, when it is presumed treatment will be more effective.In this context of 'screening,' the contract between the doctor and the patient has an ethical element not present in ordinary clinical diagnosis and treatment.Elaborating on this point, Thomas McKeown, in the late 1960s, wrote: When a patient seeks medical advice the doctor's position, ethically, is relatively simple: he undertakes to do his best with the knowledge and resources available to him.He cannot be criticized when the state of medical knowledge does not enable him to treat effectively or even diagnose accurately the condition for which his advice is sought; nor can he undertake in all cases to assemble the full range of facilities for investigation and treatment from which his patients might conceivably benefit.The position is quite different in screening, when a doctor or public medical authority takes the initiative in investigating the possibility of illness or disability in persons who have not complained of signs or symptoms.There is then a presumptive undertaking, not merely that abnormality will be identified if it is present, but that those affected will derive benefit from subsequent treatment or care.This commitment is at least implicit, and except for research and the protection ofpublic health, no one should be expected to submit to the inconvenience of investiga- tion or the anxieties of case-finding without the prospect of medical benefit.The obligation exists even when the patient asks to be screened, for his request is then based on the belief that the procedure is of value, and if it is not it is for the medical people to make this known.'
Angiotensin II–Induced Hypertension Accelerates the Development of Atherosclerosis in ApoE-Deficient Mice
Authors: Daiana Weiss, John J. Kools, W. Robert Taylor
Journal: Circulation (2001)

Background —Angiotensin II may contribute to the development and progression of atherosclerotic lesions because of its growth and proinflammatory effects. We sought to determine whether angiotensin II–induced hypertension would augment and accelerate the development of atherosclerotic lesions in apoE-deficient mice. Methods and Results —Angiotensin II (0.7 mg · kg −1 · d −1 SC) was administered to apoE-deficient mice via osmotic minipumps. The animals were placed on either standard chow or an atherogenic diet. After 8 weeks, the mean atherosclerotic lesion area in the descending thoracic and abdominal aortas of animals on a standard chow diet was 0.4±0.1% compared with 5.2±1.2% in those animals maintained on an atherogenic diet ( P &lt;0.0001). In angiotensin II–treated animals on standard chow, the mean lesion area was increased to 11.0±2.3%, which was further increased to 69.9±9.4% ( P &lt;0.0001) in angiotensin II–treated animals on an atherogenic diet. Similar findings were obtained when tissues from the ascending aorta were analyzed. At 8 weeks in mice receiving a standard chow diet, angiotensin II dramatically increased the atherosclerotic lesion area by 840±83 μm 2 ( P &lt;0.0001). Animals on a high-fat diet had a similar marked increase in lesion area in response to angiotensin II (217±19 μm 2 , P &lt;0.0001). In contrast, when hypertension was induced with norepinephrine, only a modest effect on the atherosclerotic lesion area was observed. Conclusions —Angiotensin II–induced hypertension specifically increased the development of atherosclerosis in apoE knockout mice. This response was seen in animals receiving either standard chow or an atherogenic diet. These studies demonstrate the profound effect of angiotensin II on the development of atherosclerosis.
Fibroblast Growth Factor Receptor Inhibition Is Active against Mesothelioma and Synergizes with Radio- and Chemotherapy
Authors: Karin Schelch, Mir A. Hoda, Thomas Klikovits, Julia Münzker, Bahil Ghanim, Christina Wagner, Tamas Garay, Viktoria Laszlo, Ulrike Setinek, Balazs Dome, Martin Filipits, Christine Pirker, Petra Heffeter, Edgar Selzer, Jozsef Tovari, Szilvia Torok, Istvan Kenessey, Klaus Holzmann, Bettina Grasl-Kraupp, Brigitte Marian, Walter Klepetko, Walter Berger, Balazs Hegedus, Michael Grusch
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Malignant pleural mesothelioma is an aggressive malignancy characterized by frequent resistance to chemo- and radiotherapy, poor outcome, and limited therapeutic options. Fibroblast growth factors (FGFs) and their receptors are potential targets for cancer therapy, but their significance in mesothelioma has remained largely undefined.To investigate the antimesothelioma potential of FGF receptor 1 (FGFR1) inhibition.Expression of FGFs and their receptors was analyzed in mesothelioma cell lines and tissue specimens. Several cell models were used to investigate FGFR1 inhibition in vitro and in combination with cisplatin and irradiation. Mouse intraperitoneal xenotransplant models were used for in vivo validation.FGFR1, FGF2, and FGF18 were overexpressed in mesothelioma. Stimulation with FGF2 led to increased cell proliferation, migration, and transition to a more sarcomatoid phenotype in subsets of mesothelioma cell lines. In contrast, inhibition of FGFR1 by a specific kinase inhibitor or a dominant-negative FGFR1 construct led to significantly decreased proliferation, clonogenicity, migration, spheroid formation, and G1 cell cycle arrest in several mesothelioma cell lines, accompanied by apoptosis induction and decreased mitogen-activated protein kinase pathway activity. Reduced tumor growth, proliferation, mitogenic signaling, and apoptosis induction were observed in vivo. Inhibition of FGFR1 synergistically enhanced the cytotoxic effects of ionizing radiation and cisplatin.Our data suggest that the malignant phenotype of mesothelioma cells depends on intact FGF signals, which should be considered as therapeutic targets with a promising chemo- and radiosensitizing potential.
Clinically indicated and routine replacement of peripheral IV catheters did not differ for phlebitis
Authors: Dennis G. Maki
Journal: Annals of Internal Medicine (2013)

Source Citation Rickard CM, Webster J, Wallis MC, et al. Routine versus clinically indicated replacement of peripheral intravenous catheters: a randomised controlled equivalence trial. Lancet. 2012;380:1066-74. 22998716