tbuckley/cabot-search huggingface dataset:
Spiral Computed Tomography Is Comparable to Angiography for the Diagnosis of Pulmonary Embolism
Authors: ELISABETH M. BAILE, GREGORY G. KING, NESTOR L. MÜLLER, YULIA D'YACHKOVA, EMMANUEL E. COCHE, PETER D. PARÉ, JOHN R. MAYO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The use of spiral computed tomography (CT) for the diagnosis of pulmonary embolism has been compared to angiography, the current gold standard. However, the accuracy of pulmonary angiography has never been evaluated against an independent gold standard. The aim of this study was to compare contrast-enhanced spiral CT to pulmonary angiography for the detection of subsegmental-sized pulmonary emboli by using a methacrylate cast of porcine pulmonary vessels as an independent gold standard. We studied 16 anesthetized, juvenile pigs and injected colored methacrylate beads (3.8 mm, small; 4.2 mm, large) via the jugular vein. After embolization spiral CT (3 mm and 1 mm collimation), and pulmonary angiography were performed. Pigs were killed and the pulmonary arterial tree was cast using methacrylate. Spiral CT and angiography were interpreted independently by two radiologists. Sensitivity and 95% confidence intervals for 3 mm and 1 mm collimation CT and angiography, respectively, were: 82% (73 to 88%), 87% (79 to 93%), 87% (79 to 93%) (p = 0.42). Positive predictive values and 95% confidence intervals for 3 mm and 1 mm collimation CT and angiography, respectively, were: 94% (86 to 94%), 81% (73 to 88%), and 88% (80 to 93%). There was no difference between spiral CT and angiography for detection of subsegmental-sized pulmonary emboli. We conclude that spiral CT is comparable to angiography for detection of pulmonary emboli. Baile EM, King GG, Müller NL, D'yachkova Y, Coche EE, Paré PD, Mayo JR. Spiral computed tomography is comparable to angiography for the diagnosis of pulmonary embolism.
Role of 1,2-sn diacylglycerol in airway smooth muscle stimulated by carbachol.
Authors: F Roux, E Mavoungou, E Naline, H Lacroix, C Tordet, C Advenier, B M Grandordy
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Activation of muscarinic receptors in airway smooth muscle leads to breakdown of membrane polyphosphoinositides. In agreement with others, we show here that muscarinic stimulation elicits inositol-1,4,5-triphosphate formation. In addition, we show that carbachol also elicits total diacylglycerol and 1,2-sn diacylglycerol accumulation in a specific and dose-dependent manner (EC50 values: 2.1 x 10(-8) M for 1,2-sn diacylglycerol). The time-course of inositol-1,4,5-triphosphate accumulation is compatible with that of the clonic phase of muscle contraction. Since this derivative can mobilize intracellular Ca2+ stores, it may play a second-messenger role in the initial phase of contraction. The time-course of diacylglycerol accumulation is compatible with the muscarinic-induced tonic phase of smooth-muscle contraction. Carbachol induces similar dose-dependent reductions in isoproterenol-induced muscle relaxation (EC50 values for relaxation concentration-response curves to isoproterenol: 3 x 10(-6) M and 2.1 x 10(-5) M, with carbachol at 10(-7) M and 10(-4) M, respectively), and increases in adenylate cyclase activity (EC50 values for the concentration-response to isoproterenol: 1.2 x 10(-6) M and 1.5 x 10(-5) M, with carbachol at 10(-7) M and 10(-4) M, respectively). Since it is known that carbachol-induced uncoupling of beta 2-adrenergic receptors is proportional to the breakdown of polyphosphoinositides, and that 1,2-sn diacylglycerol is a potent activator of protein kinase C, 1,2-sn diacylglycerol could be mediating the uncoupling of beta 2-adrenergic receptors, via activation of alpha-protein kinase C and subsequent phosphorylation of receptor, and/or cyclase, and/or G proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
The Role of Medicine: Dream, Mirage, or Nemesis?
Authors: Hugh H. Hussey
Journal: JAMA (1977)

McKeown's monograph assembles and amplifies, in one text, ideas he has long held about the importance of "the preservative" as compared to "the mechanistic" approach to human health. The preservative approach includes all measures that promote the public health, such as population control, provision of adequate nutrition, and protection from environmental hazards, including exposure to infective organisms. The mechanistic approach, on which much of medical practice and research is based, favors the view that human health depends on understanding the structure and function of the body and the diseases that affect it. Although McKeown does not denigrate the value of the latter approach to the person, his thesis emphasizes the greater importance of "preservation" to mankind. Following an introduction, part 1 of the book examines the determinants of health. The first chapter of this section classifies diseases into conditions determined at fertilization (genetic diseases, other diseases determined at fertilization) and
Green fluorescent protein (GFP) as a marker of aryl hydrocarbon receptor (AhR) function in developing zebrafish (Danio rerio).
Authors: C J Mattingly, J A McLachlan, W A Toscano
Journal: Environmental Health Perspectives (2001)

We developed an inducible in vivo reporter system to examine expression of the aryl hydrocarbon receptor (AhR) during development in zebrafish (Danio rerio). AhR is a ligand-activated transcription factor that mediates the toxic actions of environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Induction of cytochrome P4501A1 (CYP1A1) is an early biomarker of AhR activation. A 1905 base pair region of the human CYP1A1 promoter/enhancer region was regulated by AhR in zebrafish liver cells after exposure to TCDD (10 nM) in a transient transfection assay. This regulatory region was fused to the cDNA sequence encoding green fluorescent protein (GFP) of jellyfish (Aequorea victoria). Transgenic zebrafish were generated to express this AhR-regulated GFP construct. Injected fish exposed to TCDD exhibited induction of GFP in the eye, nose, and vertebrae of zebrafish embryos (48 and 72 hr after fertilization) compared to vehicle controls (DMSO), which did not express GFP. To investigate whether AhR-regulated GFP expression correlated with sites of TCDD toxicity, we exposed wild-type zebrafish to DMSO or TCDD and examined them for morphologic abnormalities. By 5 days after fertilization, TCDD-exposed fish exhibited gross dysmorphogenesis in cranio-facial and vertebral development.
Exogenous protoporphyrin inhibits Hep G2 cell proliferation, increases the intracellular hydrogen peroxide concentration and causes ultrastructural alterations
Authors: Jacob C. Koningsberger, Loek H.P.M. Rademakers, Jan van Hattum, Harold Baart de la Faille, Lucietta J.J.M. Wiegman, Erna Italiaander, Gerard P. van Berge Henegouwen, Jo J.M. Marx
Journal: Journal of Hepatology (1995)
PAC1 receptor–deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance
Authors: Françoise Jamen, Kristin Persson, Gyslaine Bertrand, Nieves Rodriguez-Henche, Raymond Puech, Joël Bockaert, Bo Ahrén, Philippe Brabet
Journal: Journal of Clinical Investigation (2000)

Pituitary adenylate cyclase–activating polypeptide (PACAP) is a ubiquitous neuropeptide of the vasoactive intestinal peptide (VIP) family that potentiates glucose-stimulated insulin secretion. Pancreatic β cells express two PACAP receptor subtypes, a PACAP-preferring (PAC1) and a VIP-shared (VPAC2) receptor. We have applied a gene targeting approach to create a mouse lacking the PAC1 receptor (PAC1–/–). These mice were viable and normoglycemic, but exhibited a slight feeding hyperinsulinemia. In vitro, in the isolated perfused pancreas, the insulin secretory response to PACAP was reduced by 50% in PAC1–/– mice, whereas the response to VIP was unaffected. In vivo, the insulinotropic action of PACAP was also acutely reduced, and the peptide induced impairment of glucose tolerance after an intravenous glucose injection. This demonstrates that PAC1 receptor is involved in the insulinotropic action of the peptide. Moreover, PAC1–/– mice exhibited reduced glucose-stimulated insulin secretion in vitro and in vivo, showing that the PAC1 receptor is required to maintain normal insulin secretory responsiveness to glucose. The defective insulinotropic action of glucose was associated with marked glucose intolerance after both intravenous and gastric glucose administration. Thus, these results are consistent with a physiological role for the PAC1 receptor in glucose homeostasis, notably during food intake.
Normal variations in rate of albumin excretion and albumin to creatinine ratios in overnight and daytime urine collections in non-diabetic children.
Authors: D J Rowe, H Bagga, P B Betts
Journal: BMJ (1985)

Urine albumin excretion measured over consecutive weekends and on repeated first morning collections from normal children showed considerable variation both during the day and from day to day in each subject. The results emphasise the need for repeated measurement of albumin excretion in children to confirm the presence of persistent microalbuminuria.
Type 2 Cytokines in the Pathogenesis of Sustained Airway Dysfunction and Airway Remodeling in Mice
Authors: Richard Leigh, Russ Ellis, Jennifer N. Wattie, Jeremy A. Hirota, Klaus I. Matthaei, Paul S. Foster, Paul M. O'Byrne, Mark D. Inman
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The mechanisms underlying airway hyperresponsiveness remain unclear, although airway inflammation and remodeling likely play important roles. We have observed sustained airway hyperreactivity and airway remodeling occurring in mice after chronic allergen exposure and persisting beyond resolution of allergen-induced inflammation. The aim of this study was to delineate mechanisms involved in allergen-induced airway hyperreactivity and airway remodeling and to examine evidence for a causal association between airway remodeling and sustained airway hyperreactivity. Wild-type (WT) and interleukin (IL)-4-, IL-5-, and IL-13-deficient (-/-) mice were sensitized and studied 4 weeks after chronic allergen exposure. By measuring airway responsiveness and airway morphometry, we demonstrated that WT mice developed sustained airway hyperreactivity and aspects of airway remodeling after chronic allergen exposure. Both IL-4(-/-) and IL-13(-/-) mice were protected from developing sustained airway hyperreactivity and aspects of airway remodeling. In contrast, IL-5(-/-) mice developed sustained airway hyperreactivity and aspects of airway remodeling similar to that seen in WT mice. Our results confirm that IL-4 and IL-13, but not IL-5, are critical for the development of sustained airway hyperreactivity and airway remodeling after allergen exposure.
Give-Away Medical Journals
Authors: Donald R. Silverman
Journal: JAMA (1971)

<h3>To the Editor.—</h3> I agree wholeheartedly with Greenwald on "Give-Away Medical Journals" (<b>217</b>:1705, 1971). As a busy, practicing physician, I find it quite difficult to keep up with my "required" reading consisting of two specialty journals, two general medical journals, and a journal of abstracts. I have been amazed at the increased number of "give-away" medical magazines that have appeared on the scene in the last two or three years. I would like to suggest a poll, to determine whether a significant number of physicians appreciate receiving this type of material or would prefer to see it discontinued. One would hope that these opinions would be passed on to the advertisers using these magazines and that this waste of paper and postage would come to an end.
European Commission will look at which pictures work best to help smokers quit
Authors: N. Stafford
Journal: BMJ (2009)

The European Commission is planning a new study aimed at developing better graphic images to warn of the damaging effects of tobacco, in a bid to encourage more European Union countries to put the pictures on cigarette packets.

Haravgi-Nina Papadoulaki, spokeswoman for the EC’s commissioner for health and consumer protection, Philippe Brunet, said that, although the commission developed a library of pictorial health warnings in 2005, only three European Union member states have started putting the images on cigarette packets: the United Kingdom, Belgium, and Latvia.

The commission has already asked researchers to submit proposals for the new …
Current Status of Anabolic Steroids
Authors: Alice E. Fruehan
Journal: JAMA (1963)

The clinical usefulness of anabolic agents—testosterone and the newer synthetic steroids—has not been clearly defined. After re-examining their position regarding the status of these drugs, the authors conclude that these agents are useful when specific clinical indications exist. Effective use of these compounds depends upon a knowledge of the anabolic effects desired, of the recommended dosage schedule of the drug selected, and of the side effects and contraindications. In the majority of cases, when a clinically effective anabolic agent is needed, the synthetic steroids available at present do not appear to offer any pronounced advantages over the proper use of testosterone.
For Rossi, on Admission to Medical School
Authors: Rae Varcoe
Journal: Annals of Internal Medicine (2010)

Ad Libitum6 July 2010For Rossi, on Admission to Medical SchoolRae Varcoe, MA, MBChBRae Varcoe, MA, MBChBFrom Auckland, New Zealand.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-1-201007060-00009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail on this last day of my doctoringI give you my guessing tubes,my blue, not new, stethoscopeit is a Littmanbought in Bostonwith Cynthia in 1987it has heard the whole range of murmurs,clicks, taps, knocks, plops, opening snapsand also Morris Minor piston slapit has heard first breathslast breathsand no breathsbetween my earsit has generated interest,pride, puzzlement, and fearby the time you graduateit may be obsolete,and auscultation all electronicbut keep it discretelydo not flaunt itor misread this giftI give it to remind youthat the essence of medicinelies in listeningRae Varcoe, MA, MBChBAuckland, New Zealand Author, Article, and Disclosure InformationAffiliations: From Auckland, New Zealand.Current Author Address: Rae Varcoe, MA, MBChB, Karaka Bay, Peacock Street, Glendowie, Auckland, New Zealand. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 July 2010Volume 153, Issue 1Page: 44KeywordsAuscultationFearGraduate medical education ePublished: 6 July 2010 Issue Published: 6 July 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Estrogen-like Activity of Digitalis
Authors: Ali Navab
Journal: JAMA (1965)

Vaginal smears of 52 postmenopausal women who had been taking digitoxin for periods of three months to 15 years were studied for possible estrogen-like effect on epithelial maturation. The pattern of cells from 20 women who had been taking digitoxin for over two years showed marked maturation of vaginal squamous epithelium, closely simulating the effect of estrogens. Of the 32 women who had been taking digitoxin less than two years, only three showed marked maturation of the squamous epithelium. Four of the 50 control patients exhibited moderate estrogenic effect. None showed marked maturation of vaginal epithelium.
Abstract 3517: Complete remission of xenograft tumor in nude mice induced by N-mustard-quinoline conjugates bearing hydrazinecarboxamide linker
Authors: Tsann-Long Su, Rajesh Kakadiya, Huajin Dong, Amit Kumar, Te-Chang Lee, Tung-Hu Tsai, Ting-Chao Chou
Journal: Cancer Research (2010)

Abstract Designing DNA-directed alkylating agents is a promising strategy to overcome the drawbacks of alkylating agents by enhancing DNA specific cross-linking and reducing the chemical reactivity of N-mustard. These compounds are generally synthesized by linking the alkylating warhead (such as alkyl or phenyl N-mustard pharmacophore) to the DNA-affinic carrier (such as DNA intercalating or groove binding agents). Recently, we reported that N-mustard-9-anilinoacridine conjugates via a urea, carbamate, or carbonate linker exhibited potent cytotoxicity and therapeutic efficacy against various human tumor xenografts indicating that these linkers are able to stabilize the reactive alkylating war head. Thus, these derivatives have a long half-life in plasma. Some of these conjugates are able to induce complete tumor remission (CR) in inhibiting human tumor xenograft model with low toxicity. To continue our research in finding potent DNA-directed alkylating agents, we have recently synthesized a series of N-mustard-quinoline conjugates bearing a hydrazinecarboxamide linker. These conjugates were prepared in good yield by the condensation of appropriate 4-hydrazinoquinolines with 4-bis(2-chloroethyl)- aminophenyl isocynate. The results showed that these conjugates possessed significant cytotoxicity against human lymphoblastic leukemia (CCRF-CEM) and various solid tumor xenografts (such as MX-1, HCT-116, H1299, CL 1-0, CL 1-5, PC3 and MCF-7) cell growth in vitro. Among these agents, BO-1392 and BO-1393 were able to induce CR against human breast carcinoma MX-1 xenograft and significantly suppress against human ovarian SK-OV3 xenograft in animal model with relative low toxicity. Interestingly, we found that BO-1393 (iv. injection) can significantly prolong the life span of nude mice bearing human glioma SK-NA-S xenograft (orthotropic implanted in brain). The experiment was compared with Temozolomide (oral administration). The modified comet assay and alkaline agarose gel shift assay showed that these conjugates are capable of inducing DNA interstrand cross-linking in human non-small lung cancer H1299 cells. In conclusion, the present studies demonstrated that the newly synthesized N-mustard-quinoline conjugates having a hydrazinecarboxamide linker exhibited a broad spectrum of antitumor activity and are chemically stable. The remarkable therapeutic efficacy of BO-1393 demonstrated that this agent has high potential for clinical development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3517.
Unilateral Dilated Pupil From Scopolamine Disk
Authors: John A. Carlston
Journal: JAMA (1982)

To the Editor.—  We recently took a family trip to Mexico. While sitting on a bright, sunny terrace one morning at 11 AM, my 20-year-old daughter was accused of having a funny eye by her sister. On examination, her left pupil was completely dilated, in contrast to her small right pupil. The dilated pupil did not appear to react to light or accommodation; however, back in the hotel room, a bright light increased the thin rim of iris from perhaps 1.5 mm to 2 mm at most. There was no history of familial aneurysm, no head trauma, no nuchal rigidity, and no visual defect in that eye; in fact, I could ascertain nothing else abnormal. She had not used any eyedrops, and her only known medication was prophylactic doxycycline.  A telephone call to her ophthalmologist in the United States elicited the routine question, Any atropine drugs? Then the light dawned.
Good Medical Care Is Caring
Authors: William R. Barclay
Journal: JAMA (1978)

Infrequently is an article written by a patient or member of a patient's family published inThe Journal. However, the contribution from Mary Kate House in this issue (p 2472) is an exception, for it is filled with wisdom and sound practical advice. She describes ideal care for the elderly and chronically ill in the environment of the patient's home, with devoted ministrations from the family members and friends. No nursing home, no staff of experts, and no government health scheme can provide the quality of care described in this article. Medical care is more than the application of technology and knowledge. It is, first of all, caring, and this component of medicine seems to be missing from much of what we do today. Most neglected in this respect are the elderly ill and the incurable. Placed in long-term care facilities, they are often neglected by their physicians and their
Who votes for NOTES?
Authors: T. Rosch
Journal: Gut (2008)

On the verge of something new and exciting, it is always difficult to make predictions: this may be especially true for NOTES which stands for natural orifice transluminal endoscopic surgery, and is represented by societies and initiatives with similarly ingeniously invented acronyms (NOSCAR = Natural Orifice Surgery Consortium for Assessment and Research).1 Perhaps for fear of being left behind, societies are formed on a national and international basis. Training courses are held on something which—frankly speaking—does not exist yet. At least not in humans outside of a few transvaginal cholecystectomy and appendectomy case reports and series.2–9 Recently, in addition, a first series on transumbilical flexible endoscopic cholecystectomy has been reported with somewhat disappointing results10; transgastric cholecystectomy appears to be on the way.

NOTES raises a number of questions, both fundamental ones with regards to indications and risk assessment as well as those related to technical issues. These will be outlined and discussed in the following.

Many think that the greatly reduced invasivensss of laparoscopic as compared with open surgery will be further diminished by NOTES and serve as one of its justifications. At the time when laparoscopic cholecystectomy was invented, there was probably almost no perceived need at all, since almost everybody was convinced that the open procedure was perfect. Indeed, it took some time till the higher complication rate of the laparoscopic as compared with the open approach levelled off. Finally, less invasiveness, less pain and better patient comfort with laparoscopic surgery were also proven in comparative trials, mostly for benign disease.11

The degree of use of the laparoscopic approach varies between countries because environmental factors play a role, independently of the intrinsic value of the procedure. Figures from worldwide surveys, however, confirm a predominance of laparoscopic cholecystectomy12 and also a sharply increasing …
Oncolytic effects of adenovirus mutant capable of replicating in hypoxic and normoxic regions of solid tumor
Authors: Won-Kyung Cho, Young Rim Seong, Yeune Hee Lee, Min Ji Kim, Kyung-Sun Hwang, Jinsang Yoo, Seeyoung Choi, Cho-Rok Jung, Dong-Soo Im
Journal: Molecular Therapy (2004)

Solid tumors contain normoxic and hypoxic regions depending on the distance from the capillary. Normal cells may also be exposed to hypoxia under certain physiological conditions. Tumor hypoxia has been shown to associate strongly with tumor propagation and malignant progression. Hypoxia-inducible factor (HIF)-1alpha is stable under hypoxia and induces transcription of target genes by binding to the hypoxia-response element (HRE). Here we investigated the oncolytic effects of a novel adenovirus mutant with a deleted E1B55 gene (Ad.Delta55.HRE), in which the expression of E1A, which is essential for adenoviral replication, is regulated under the control of an HRE-expression system. Ad.Delta55.HRE expressed E1A under normoxia and more E1A under hypoxia and exhibited oncolytic effects on various cultured tumor cells, but its cytotoxic effect is relatively attenuated in normal fibroblast cells under normoxic and hypoxic conditions. Ad.Delta55.HRE lysed Huh-7 hepatoma cells stably expressing HIF-1alpha more effectively compared to parental cells. Ad.Delta55.HRE treatment exhibited significant antitumor activity in PC-3 prostate- and MDA-MB-435 breast tumor-bearing nude mice in which HIF-1alpha protein was immunohistochemically detected. The E1A and hexon proteins of adenovirus were immunostained in MDA-MB-435 xenografts after Ad.Delta55.HRE treatment, suggestive of viral replication. Our results suggest that Ad.Delta55.HRE may be useful for the treatment of solid tumors.