tbuckley/cabot-search huggingface dataset:
Inappropriateness of randomised trials for complex phenomena
Authors: Mary Hannah
Journal: BMJ (2005)

Evidence based medicine: does it make a difference? Use wiselyEditor-The term "evidence based medicine" entered the scientific lexicon only a little more than a decade ago. 1 What caused its remarkable spread, and what are the implications of its broad and rapid diffusion?The team that coined the term at first considered using the phrase "scientific medicine" but rejected it because it implied that other approaches were by definition unscientific. 2However, critics have argued that the term evidence based medicine carries a similar moral valence and linguistic slipperiness. 3 Who could argue against the notion of providing care that integrates individual clinical skill and the best external evidence? 4 Originally developed as a method for teaching medical residents, evidence based medicine is being applied ever more broadly to the organisation and delivery of medical services.Multiple stakeholders now seek to assume its mantle for purposes that often contradict its original intent.Managers, equating lack of evidence with lack of effectiveness, use it as a rationale for cutting services.Industry generates evidence of questionable quality to promote its products.Medical researchers come to believe that they hold a monopoly on generating and interpreting evidence.Evidence based medicine, developed as a means of taming the unscientific and messy world of clinical practice, has itself entered the unscientific and messy world of politics. 5ike any technology, evidence based medicine carries risks and benefits and can be used appropriately or inappropriately.Overly inclusive definitions threaten to deprive the term of meaning, and unchecked use increases the risk of misuse.In the past decade, evidence based medicine has contributed much to how we teach, deliver, and think about clinical services.In the coming decade, we must continue to ensure that it is not only used widely but wisely.
Studies of human C5a as a mediator of inflammation in normal human skin.
Authors: K B Yancey, C H Hammer, L Harvath, L Renfer, M M Frank, T J Lawley
Journal: Journal of Clinical Investigation (1985)

C5a is an 11,000-D fragment of the fifth component of complement (C5) with potent anaphylatoxic and leukocyte chemotactic activities. C5a is believed to play an important role in the pathophysiology of certain skin disorders and systemic diseases with cutaneous manifestations. However, there is very little known about the in vivo reactivity of C5a in man. In this study we examined the effects of intradermal injections of human C5a in 17 normal volunteers. C5a was prepared by interacting highly purified human C5 with zymosan bound alternative pathway C5 convertase under conditions resulting in consumption of approximately 90% of the C5 substrate. C5a produced in this manner was chemotactic for human neutrophils and monocytes (0.5 X 10(-7) to 10(-9) M) and caused neutrophil aggregation and myeloperoxidase release (concentrations greater than or equal to 10(-10) M) in vitro. In vivo, C5a produced immediate wheal and flare reactions in all volunteers, and was active in doses as low as 1 ng (10(-13) mol). Intradermal testing with 20 ng of C5a in eight volunteers produced a maximal mean wheal of 11.75 mm (+/- 0.80 mm SEM) 20 min after anaphylatoxin injection, and a maximal mean erythema of 62.50 mm (+/- 3.27 mm SEM) 10 min after C5a administration. Reactions at C5a test sites were dose-related, associated with marked pruritus in some subjects, resolved without lesion formation, and were not associated with late phase reactions. In vivo testing revealed that human C5a was a more potent mediator of wheal and flare reactions than histamine, 48/80, human C3a, or morphine sulfate. Skin biopsies from eight volunteers 20 min after intradermal injection of 20 ng of C5a revealed a neutrophil-predominant perivascular infiltrate, endothelial cell edema, and sites of leukocytoclasis. Mast cell degranulation was observed on both light and electron microscopy of biopsies from C5a test sites. Although erythema at C5a injection sites was reduced by pretreating volunteers with hydroxyzine, whealing reactions and cellular infiltrates in biopsies were unaffected by this H1-antihistamine. Moderate doses of systemic corticosteroids did not alter clinical or histologic reactions at C5a injection sites in two volunteers. This study, using doses within the potential physiologic range of the anaphylatoxin, provides a comprehensive assessment of the effect of human C5a on normal human skin.
Neutrophil kinetics in the dog.
Authors: K A Deubelbeiss, J T Dancey, L A Harker, C A Finch
Journal: Journal of Clinical Investigation (1975)

The production of neutrophils in dogs has been estimated from the number of postmitotic neutrophils in the marrow and the transit time of a [3H]-thymidine pulse. The number of postmitotic neutrophils was derived from the erythron iron turnover measurement of erythroid number and the neutrophil-erythroid ratio in bone marrow sections. The mean value for marrow postmitotic neutrophils in dogs was 5.61 plus or minus 0.56 times 10-9 cells/kg. The mean transit time of these neutrophils was calculated to be 82.1 h. A marrow production of 1.65 times 10-9 neutrophils/kg/day was calculated from these data. The turnover of circulating neutrophils was measured by [3H]thymidine and [32P]diisopropylphospho-fluoridate (DF32P) labeling of blood neutrophils. [3H]-Thymidine labeling gave a calculated recovery of 65 per cent, a t1/2 disappearance time of 6.7 h, and a calculated turnover of 1.66 times 10-9 cells/kg/day. Corresponding results with DF32P tagging were 51 per cent, 5.4 h, and 2.89 times 10-9 cells/kg/day. The discrepancy between these two tags persisted in doubly tagged cells and was considered to be due to elution of DF32P.
Clinical Application of an Improved, Rapidly Responding Intravascular Fiber-Optic Catheter.
Authors: Peter L. Frommer
Journal: Annals of Internal Medicine (1965)

s1 November 1965Clinical Application of an Improved, Rapidly Responding Intravascular Fiber-Optic Catheter.Peter L. Frommer, M.D., John Ross Jr., M.D., Dean T. Mason, M.D., James H. Gault, M.D., Eugene Braunwald, M.D., F.A.C.P.Peter L. Frommer, M.D.Search for more papers by this author, John Ross Jr., M.D.Search for more papers by this author, Dean T. Mason, M.D.Search for more papers by this author, James H. Gault, M.D.Search for more papers by this author, Eugene Braunwald, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-903_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe development of an accurate, stable, rapidly responding (0.1 sec time constant) fiber-optic catheter system, based on reflectance oximetry, now permits direct continuous recording of intracardiac oxygen saturation and indocyanine green dye concentration without the withdrawal of blood. Oxygen saturation has been recorded continuously for periods of up to 3 hours in 17 patients with congenital or valvular heart disease. The catheter oximeter facilitated precise localization as well as the quantification of left-to-right shunts. Further, it was observed that the flow through ventricular septal defects occurs predominantly during systole, while flow across atrial septal defects varies phasically with both the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, Maryland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 903-903KeywordsAtrial septal defectAttentionBloodCardiovascular therapyCathetersCongenital heart defectsOxygenSystoleVentricular septal defects Issue Published: 1 November 1965 PDF downloadLoading ...
Reducing the Illegal Sale of Cigarettes to Minors
Authors: David G. Altman
Journal: JAMA (1989)

This study reports on an effort to stop the illegal sale of cigarettes to minors. In Santa Clara County, Calif, 412 stores and 30 vending machines were visited by 18 minors aged 14 through 16 years with the intent to purchase cigarettes; they were successful at 74% of the stores and 100% of the vending machines. After an aggressive six-month campaign using communitywide media, direct merchant education, contact with the chief executive officers of chain stores and franchise operations owned by major companies, and grassroots work with community organizations, the percentage of stores with illegal over-the-counter sale of cigarettes to minors was reduced to 39%. Sales from vending machines were not reduced. While much remains to be accomplished in stopping the illegal sale of tobacco to minors, data from this study illustrate that a well-designed community and merchant education campaign can significantly reduce such sales. (<i>JAMA</i>1989;261:80-83)
Low-Back Pain: A Psychosomatic Clinical Study
Authors: H.-P. Villard, J. Imbeault, M. Duguay
Journal: Psychotherapy and Psychosomatics (1986)

Most studies relating psychological factors to low-back pain have been done on subjects already referred to psychiatry. This study addresses 27 patients who had undergone their first lumber discoidectomy and never had any contact with psychiatry. They were submitted to a threefold assessment in order to find psychosocial criteria that could discriminate good- from bad-outcome subjects. It was found that a bad outcome was related to: (1)a difficulty in perceiving and expressing affects, (2) some financial compensation, (3) high rating on pain assessment tests.
Management of Cancer of the Head and Neck — A Cocktail with Your PORT?
Authors: Michele I. Saunders, Ana M. Rojas
Journal: New England Journal of Medicine (2004)

Squamous-cell cancer of the head and neck is the sixth most common cancer worldwide, with a lifetime risk of 2 percent for men and 0.6 percent for women. There are approximately 76,000 and 37,000 new cases of oral-cavity, pharyngeal, and laryngal cancer diagnosed each year in Western Europe and the United States, respectively. The presence or absence of local and regional disease primarily determines the treatment outcome among these patients. Nonetheless, although the incidence of distant metastases is relatively low, as compared with that of other cancers of the upper aerodigestive tract, distant metastases will develop in almost one third . . .
Cellular immune mechanisms in rheumatoid arthritis and Sjogren's syndrome.
Authors: K Whaley, A C Glen, S D Deodhar, W C Dick, G Nuki, W W Buchanan
Journal: Annals of the Rheumatic Diseases (1971)

evidence of vasculitis, as shown, for instance, in the fingers, because if there was a correlation here, arterial oblitera- tion might well explain a decrease in renal function.DR. BURRY This is an important omission.We did not see any nail-fold lesions in the whole series of 97 cases, nor evidence of arteritis in the renal biopsies.DR.K. WHALEY (Glasgow) Did you screen your patients for keratoconjunctivitis sicca?Sjogren's syndrome is occasionally complicated by glomerulonephritis, and it would be interesting to know whether the diminished creatinine clearance is related to keratozonjunctivitis si -ca.DR.BURRY There were no cases of Sjogren's syndrome.
Augmentation of pulmonary reactions to quartz inhalation by trace amounts of iron-containing particles.
Authors: V Castranova, V Vallyathan, D M Ramsey, J L McLaurin, D Pack, S Leonard, M W Barger, J Y Ma, N S Dalal, A Teass
Journal: Environmental Health Perspectives (1997)

Fracturing quartz produces silica-based radicals on the fracture planes and generates hydroxyl radicals (.OH) in aqueous media. .OH production has been shown to be directly associated with quartz-induced cell damage and phagocyte activation in vitro. This .OH production in vitro is inhibited by desferrioxamine mesylate, an Fe chelator, indicating involvement of a Fenton-like reaction. Our objective was to determine if Fe contamination increased the ability of inhaled quartz to cause inflammation and lung injury. Male Fischer 344 rats were exposed 5 hr/day for 10 days to filtered air, 20 mg/m3 freshly milled quartz (57 ppm Fe), or 20 mg/m3 freshly milled quartz contaminated with Fe (430 ppm Fe). High Fe contamination of quartz produced approximately 57% more reactive species in water than quartz with low Fe contamination. Compared to inhalation of quartz with low Fe contamination, high Fe contamination of quartz resulted in increases in the following responses: leukocyte recruitment (537%), lavageable red blood cells (157%), macrophage production of oxygen radicals measured by electron spin resonance or chemiluminescence (32 or 90%, respectively), nitric oxide production by macrophages (71%), and lipid peroxidation of lung tissue (38%). These results suggest that inhalation of freshly fractured quartz contaminated with trace levels of Fe may be more pathogenic than inhalation of quartz alone.
Magnetic Compression Anastomosis for Benign Obstruction of the Common Bile Duct
Authors: S. Takao, Y. Matsuo, H. Shinchi, S. Nakajima, T. Aikou, T. Iseji, E. Yamanouchi
Journal: Endoscopy (2001)

Advances in interventional radiology have made possible magnetic compression anastomosis between the bile duct and the small intestine as a novel treatment. A 70-year-old man who had undergone subtotal gastrectomy for gastric cancer 2 years previously experienced recurring cholangitis with high fever and jaundice. Diagnostic evaluation subsequently demonstrated complete obstruction of the common bile duct which was attributed to recurrent cholangitis. A parent magnet was placed endoscopically into the afferent loop of the duodenum through the gastrojejunostomy with Billroth II reconstruction. The daughter magnet attached to a guide wire was placed in the obstructed common bile duct through a percutaneous transhepatic cholangiographic drainage tube. Two magnets were immediately attracted towards each other transmurally, and anastomosis was established on day 32 after the procedure. This novel method of magnetic compression anastomosis has the advantages of noninvasiveness and simplicity, as well as being a well-tolerated procedure for indications such as biliary obstruction.
Current toxicological information as the basis for sulfur oxide standards.
Authors: M A Mehlman
Journal: Environmental Health Perspectives (1983)

The ambient air quality standard established in 1973 is 0.03 ppm annual average for sulfur dioxide and 0.075 mg/m3 for particulates. It is now generally believed that the toxicity of sulfur oxides in ambient air is significantly influenced by the coincident presence of particulates. Inhalation of 1 ppm of sulfur dioxide for 2 hr may produce alterations in pulmonary ventilatory function, both in normal and asthmatic subjects. Effects obtained at 0.5 ppm of sulfur dioxide are controversial and of questionable biological significance. No clear evidence exists that sulfur dioxide or bisulfite causes mutagenicity in mammals, and it is concluded from a variety of animal experiments that long-term exposure to sulfur dioxide alone does not cause cancer.
A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse
Authors: S Park, N Chapuis, F Saint Marcoux, C Recher, T Prebet, P Chevallier, J-Y Cahn, T Leguay, P Bories, F Witz, T Lamy, P Mayeux, C Lacombe, C Demur, J Tamburini, A Merlat, R Delepine, N Vey, F Dreyfus, M C Béné, N Ifrah, D Bouscary
Journal: Leukemia (2013)
The Left Arm and Hand of a Child Found in a State of Putrescence, from Strangulation, the Funis Being Tightly Bound Round It at the Upper Part
Authors: A. Owen
Journal: BMJ (1851)

supply of water at all hours, for the use of the inhabitants, surely there is no excuse for any town in England remaining behind London in the promotion of such necessary sanitary measures.With regard to a supply of water, we may add, in the words of the Times, " that it is now a plain and fundamental maxim of sanitary economy, social policy, and good government that the water we use should be no more an article of trade or taxation than the air we breathe or the light we enjoy."Thanks to the exertions of the sanitary reformers we are now promised light-that boon of Heaven-without paying a tax for the use of it.
Inhibition of antibodies binding polyinosinic polycytidylic acid in human and mouse lupus sera by viral and synthetic ribonucleic acids
Authors: Norman Talal, Alfred D. Steinberg, Gerald G. Daley
Journal: Journal of Clinical Investigation (1971)

The specificities of anti-RNA antibodies of diverse origin were studied by inhibition of the binding of radioative polyinosinic polycytidylic acid. The antibodies were from human patients with systemic lupus erythematosus (SLE), older NZB/NZW F(1) mice who have SLE, and young NZB/NZW F(1) mice immunized with either synthetic or viral double-stranded (ds) RNA. The inhibitors were two viral ds and two synthetic ds RNAs, ribosomal RNA and transfer RNA. The human sera were more heterogeneous than the mouse lupus sera, and had greatest specificity for reovirus RNA. The mouse lupus sera were more homogeneous and, in general, were inhibited efficiently by all four ds RNAs. Sera from mice immunized with synthetic RNA reacted poorly with viral RNA, whereas sera from mice immunized with viral RNA reacted with all four ds RNAs and resembled the lupus sera. These results suggest a role for viruses in the induction of anti-RNA antibodies, and are compatible with the concept that virus infection as well as excessive antibody responses are involved in the pathogenesis of SLE.
JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia
Authors: Kaan Boztug, Päivi M Järvinen, Elisabeth Salzer, Tomas Racek, Sebastian Mönch, Wojciech Garncarz, E Michael Gertz, Alejandro A Schäffer, Aristotelis Antonopoulos, Stuart M Haslam, Lena Schieck, Jacek Puchałka, Jana Diestelhorst, Giridharan Appaswamy, Brigitte Lescoeur, Roberto Giambruno, Johannes W Bigenzahn, Ulrich Elling, Dietmar Pfeifer, Cecilia Domínguez Conde, Michael H Albert, Karl Welte, Gudrun Brandes, Roya Sherkat, Jutte van der Werff ten Bosch, Nima Rezaei, Amos Etzioni, Christine Bellanné-Chantelot, Giulio Superti-Furga, Josef M Penninger, Keiryn L Bennett, Julia von Blume, Anne Dell, Jean Donadieu, Christoph Klein
Journal: Nature Genetics (2014)
The Current Status of Tumor Imaging
Authors: David L. Lilien
Journal: JAMA (1974)

AMONG the most exciting advances in the treatment of malignant disease has been the dramatic improvement in survival of patients with lymphoma and Hodgkin disease.<sup>1</sup>This has been accomplished by the use of new drug combinations and sophisticated techniques for radiation therapy; drugs and irradiation are often given together or in sequence. Such an approach is being extended to other tumor types, particularly carcinoma of the breast and a variety of tumors originating in the pelvis. The choice of therapy for a given patient depends, to a critical degree, on accurate information on the extent of disease (staging). Many techniques exist for the assessment of the extent of malignant disease. They include clinical examination, laboratory tests, routine roentgenographic procedures, tomography, lymphography, ultrasound, angiography, and even exploratory surgery. The more sophisticated studies, however, may be hazardous, expensive, or not amenable to repetition necessary for assessment of the results of therapy.
The sharp end of the dural puncture
Authors: E. C Weir
Journal: BMJ (2000)

As the pain of a sudden onset dural puncture headache was searing and spreading like hot molten metal I forgot what I was there for. The pain of the contractions disappeared into the head pain. Three failed epidurals, two spinal blocks, and a few incisions into a caesarean section the head pain was all consuming, the lights surreal and too bright, and the only sound that I could hear through the ringing woolliness was my own screaming. My head. Please help me. “Patient not coping. Converted to general anaesthetic. Delivered of female infant.” 

Recovering from the anaesthetic I forgot that there had been a baby, only remembering the headache, which seemed to have gone. In morphined confusion I cried a bit and turned away from the baby, and the headache came back. “Patient lying down. Unable to care for baby. Not coping. Very upset.” 

Four days and two painful blood patches later the headache resolved enough to allow me to stand up and let light and life back in. The anaesthetist sat on my bed and stroked my hair. Tears …
Immune Privilege
Authors: Seokmann Hong, Luc Van Kaer
Journal: The Journal of Experimental Medicine (1999)

The concept of immune privilege refers to the observation that tissue grafts placed in certain anatomical sites, including the brain and eye, can survive for extended periods of time 1. Immune privilege is thought to reflect an evolutionary adaptation to protect vital structures from damage by inflammatory responses directed against pathogens. It was originally believed that antigens in immune-privileged sites are concealed from the immune system by physical barriers and therefore ignored. However, subsequent studies have shown that antigens do leave immune-privileged sites, that these antigens can induce immune responses, and that immune effector cells can have access to immune-privileged sites. It is now clear that immune privilege is maintained by an active rather than passive process 234.

The eye is an excellent example of an immune-privileged site. This organ enjoys immune privilege to protect it from destructive inflammation that may impair vision. Immune privilege in the eye is attributed to a variety of mechanisms (for reviews, see references 2–4), including lack of lymphatic drainage, low expression of MHC molecules, increased expression of surface molecules (CD59, membrane cofactor protein, and decay-accelerating factor) that inhibit complement activation, local production of immunosuppressive cytokines such as TGF-β, presence of neuropeptides, and constitutive expression of Fas ligand (FasL). The latter mechanism controls the entry of Fas-expressing lymphoid cells into the eye 5. Additionally, antigen presentation in the eye can elicit regulatory T (Tr) cells that induce immune deviation and suppress inflammatory responses, both locally and systemically (for a review, see reference 2). In this issue, Sonoda et al. 6 demonstrate that immune deviation induced by antigens placed in the anterior chamber (AC) of the eye requires CD1d-reactive natural killer T (NKT) cells. These findings provide insights into the maintenance of immune privilege and indicate that NKT cells play a critical role in the regulation of immune responses.