tbuckley/cabot-search huggingface dataset:
Treatment of Status Asthmaticus
Authors: Marc Goldberg
Journal: JAMA (1985)

To the Editor.—  The recent report by Schwartz1describing the use of halothane to treat status asthmaticus unresponsive to other therapy serves as a useful reminder to the medical community. However, several important clarifications should be made.  First, the initial treatment in case 2 was suboptimal. Clearly, arterial hypoxemia (Pao2, 61 mm Hg) and hypercarbia (Pco2, 123 mm Hg) of this magnitude, along with patient lethargy, mandate immediate mechanical ventilation. Furthermore, administration of sodium bicarbonate for the treatment of respiratory acidosis without mechanical ventilation will only produce greater hypercarbia.  Although Schwartz suggests that the use of succinylcholine is contraindicated in status asthmaticus because of histamine release, this is actually not a significant problem. Succinylcholine releases minimal amounts of histamine2; it is almost never a problem in clinical practice. A theoretical concern is its effect of activating all cholinergic autonomic receptors, thus increasing bronchospasm. A more practical
Networked disease: emerging infections in the global city
Authors: Harunor Rashid
Journal: The Lancet Infectious Diseases (2009)

Written by a score of experts from sociology through medical humanities to geography, this book discusses how the interconnected fluid network formed by the flow of cash, commodities, people, and vectors helps spread infectious diseases among cities worldwide, and what the social and political reactions are to disease spread. Although the book primarily focuses on the role of this worldwide network on the spread of severe acute respiratory syndrome (SARS), a few other diseases such as avian influenza, AIDS, and tuberculosis are discussed.
Abstract 2344: Distinct combinations of signaling pathways promote migration of MDA-MB-231 breast carcinoma cells in response to different stimuli
Authors: Susan M. Harrison, Min Chen, Teresa Knifley, Kathleen L. O'Connor
Journal: Cancer Research (2011)

Abstract Cancer cell invasion and metastasis are predicated on the activation of signaling pathways that control dynamic organization of cytoskeletal architecture. The coordinate reorganization of an actin network pushing at the leading edge and an actin-myosin mediated retraction at the rear of the cell facilitates cell polarity to allow directed movement. Motility of the highly invasive breast carcinoma cell line MDA-MB-231 is promoted by various stimuli including lysophosphatidic acid (LPA), hepatocyte growth factor (HGF) and epidermal growth factor (EGF). The goal of this project is to delineate the signaling pathways mediating motility in response to each of these stimuli. Identifying common and conditional pathways mediating cell motility has important implications for therapeutic intervention of cancer cell invasion and metastasis. We conducted migration, invasion, and morphology assays in the presence of inhibitors for pathways known to contribute to the cytoskeletal reorganization required for cell migration. LPA, HGF and EGF were evaluated for their capacity to signal through the Rho family small GTPases, Rho and Rac, the MAP kinase pathway via MEK1/2 and myosin light chain kinase (MLCK) to influence cell migration and invasion. LPA is a recognized component of breast cancer progression and potent stimulator of Rho activity, which has been extensively implicated in the migration of carcinoma cells in a variety of cancers including breast. Surprisingly, LPA-stimulated migration of MDA-MB-231 cells was not affected by Rho inhibitors but was instead sensitive to Rac inhibition. In contrast, Rho was required for HGF and EGF-stimulated migration of MDA-MB-231 cells while Rac had no effect on these processes. Other common pathways mediating cell motility including MLCK are used by all three chemoattractants. MDA-MB-231 cells employed all of the pathways examined for invasion, potentially reflecting the complexity of navigating in a three dimensional environment. These observations suggest that while multiple signaling pathways contribute to the migratory potential of a cancer cell, not all pathways are operating under all conditions. Different context-specific pathways may supplement a core of common pathways to create a functional signal but the characteristics of the response will likely rely on the particular combination used by the cell. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2344. doi:10.1158/1538-7445.AM2011-2344
Incidence of Laryngeal Involvement in Rheumatoid Arthritis
Authors: Robert H. Lofgren, William W. Montgomery
Journal: New England Journal of Medicine (1962)

IT has been well established that arthritic changes occur in the larynx. During recent years a few general discussions and case reports of cricoarytenoid arthritis have appeared in the literature.1 2 3 The incidence of involvement, however, is not well known. The joint involved in laryngeal arthritis, the cricoarytenoid joint, is arthrodial in type, with a fibrous capsule and a synovial lining. The arthritic process causes destruction of the joint lining, with irregularity of the articular surfaces and widening of the joint space, which becomes filled with fibrous tissue and fat.4 The most common etiology of cricoarytenoid arthritis is rheumatoid arthritis. It . . .
PREVENTION OF HAY FEVER.
Authors: ALEXANDER RIXA
Journal: JAMA (1899)

It is interesting to note the immense progress medical science has made in the investigation concerning the etiology, pathology and therapy of that obscure disease called hay fever. A survey of the results achieved in the last few years, in connection with a brief historic review, is highly interesting and instructive. Presumably the term "hay fever" originated in the early belief that the emanations of the new-mown hay are the cause of the disease. Hay fever is an ancient disease. The first case was reported by Botallus as early as 1565, although the early writers did not recognize it as a distinct ailment, until Dr. Bostock of London published a series of essays on the subject from 1828 to 1835, in which he describes it as a distinct, periodic, autumnal disease, which, according to his claim, is caused by the united efforts of<i>moist heat, sunshine, dust and fatigue</i>. Dr.
Hyperserotonemia and Early Infantile Autism
Authors: Roland D. Ciaranello
Journal: New England Journal of Medicine (1982)

IN this issue of the Journal, Geller and his colleagues show that the administration of fenfluramine to three autistic children lowered platelet serotonin and was followed by improvement in clinical symptoms, social behavior, and IQ.1 This finding may have important implications in the treatment of infantile autism and may cast much-needed new light on this bewildering disorder.The past 30 years have seen a marked shift in our perspective on infantile autism. In the 1950s autism was pronounced a psychologic disorder, the "rage reaction" of the child against the mother's unconscious wish that he or she did not exist. . . .
The Regulation of Discovery and Drug Development
Authors: John A. Oates, Alastair J.J. Wood
Journal: New England Journal of Medicine (1989)

Within the scope of its responsibility for commercial drug development, the Food and Drug Administration also regulates the opportunity for scientific discovery through clinical research. The agency controls the entry of all chemical compounds into clinical research, including those employed in the investigation of human physiology and disease. The process of initiating the clinical investigation of novel compounds is a critical step in therapeutic innovation. These considerations led the FDA to reevaluate and revise the regulations governing clinical research involving new drugs. The 1987 rewrite of the FDA regulations, which is described in the article by Kessler in this issue . . .
Clinical profile of autosomal dominant polycystic liver disease
Authors: Qi Qian, Airong Li, Bernard F. King, Patrick S. Kamath, Donna J. Lager, John Huston, Clarence Shub, Sonia Davila, Stefan Somlo, Vicente E. Torres
Journal: Hepatology (2003)

Most reports on the natural history, manifestations, and treatment of polycystic liver disease are based on the disease as it manifests in patients with autosomal dominant polycystic kidney disease (ADPKD). The purpose of this study was to develop a clinical profile of isolated autosomal dominant polycystic liver disease (ADPLD) using nonaffected family members as controls. The study included 146 probands, known affected relatives, and first-degree relatives of affected individuals. Participants underwent a formalized medical history interview and physical examination, ultrasonographic examination of the liver and kidneys, magnetic resonance angiography of the brain, and echocardiography. Thirty-eight of the 49 individuals diagnosed with polycystic liver disease before participation in the study were or had been symptomatic. Of 97 previously undiagnosed at-risk individuals, 23 were affected, 39 were unaffected, and 35 were indeterminate. Compared with patients with a negative or indeterminate diagnosis, those with polycystic liver disease had slightly higher levels of serum alkaline phosphatase and total bilirubin and lower levels of total cholesterol and triglycerides. Female patients had a significantly higher mean cyst score than male patients. The cysts were found to arise from the dilatation of biliary microhamartomas and from peribiliary glands. Structural mitral leaflet abnormalities were detected more frequently in affected than in indeterminate or nonaffected individuals. A vascular phenotype was detected in 5.6% of the patients with isolated ADPLD diagnosed clinically and/or by linkage analysis but in none of the unaffected patients. In conclusion, isolated ADPLD is underdiagnosed and genetically distinct from polycystic liver disease associated with ADPKD but with similar pathogenesis, manifestations, and management.
3,3'-Diindolylmethane Inhibits Activation of Akt through Inhibition of Hepatocyte Growth Factor Receptor c-Met Signaling.
Authors: H. Hantz, K. Lee, L. Bjeldanes
Journal: Cancer Research (2009)

Abstract Background: 3,3'-Diindolylmethane (DIM), the major acid condensation product of indole-3-carbinol, is a promising anticancer compound that is bioavailable, non-toxic, and easily obtainable. Although DIM has strong anticancer activity against breast cancer cells in vitro and in vivo, the exact mechanism for this activity is not known. We and others have found that DIM inhibits activation of the Akt pathway in breast cancer cells. Akt is a serine threonine protein kinase involved in many important cellular functions including proliferation and cell survival. Akt is active when phosphorylated at serine-473 and threonine-308. In breast cancer cells, Akt can be activated by various stimuli, including signaling from growth factor receptors like the hepatocyte growth factor (HGF) receptor c-Met, which is often overexpressed in breast cancer. In this project, we show that c-Met is an upstream point of inhibition of the Akt pathway by DIM.Materials and Methods: When MDA-MB-231 breast cancer cells reached 70-80% confluency, we serum-starved them by reducing the fetal bovine serum concentration in the media from 10% to 1% for 20 hours and then treated with DIM or the vehicle control DMSO for 4 hours or the indicated time. When using recombinant growth factors to activate Akt or c-Met, we incubated cells in medium containing no fetal bovine serum and added the growth factors for 10 minutes after incubation with DIM. To analyze protein expression and protein phosphorylation we performed Western blotting. To analyze c-Met kinase activity we used a commercially available kit.Results: DIM does not inhibit activation of Akt downstream of either epidermal growth factor or insulin-like growth factor-1. However, DIM does inhibit Akt activation downstream of HGF and of fetal bovine serum. DIM inhibits tyrosine phosphorylation of c-Met at Y1349 and Y1234/1235. DIM does not affect total c-Met protein or mRNA levels and does not directly inhibit c-Met kinase activity.Discussion: While we have determined that DIM inhibits c-Met phosphorlyation, and therefore HGF signaling, the mechanism of this inhibition requires further study. We hypothesize that DIM induces serine phosphorylation of c-Met, since c-Met can be inhibited by reactive oxygen species (ROS)-induced phosphorylation of serine-985 by protein kinase C (PKC), and DIM increases ROS levels in cells.Components of the Akt pathway are frequent targets for mutations in breast cancer and c-Met and its ligand HGF are associated with lower survival and increased risk of distant metastases in breast cancer. This project represents an important step in determining the mechanism of action for DIM, a promising phytochemical for the treatment of breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6117.
On Transcendental Metaworry (TMW)
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1974)

IT is said that modern, industrialized, civilized human beings are uniquely nervous and jumpy, unprecedentedly disturbed by the future, despaired by the present, sleepless at memories of the recent past, all because of the technologic complexity and noisiness of the machinery by which we are surrounded, and the rigidified apparatus of cold steel and plastic that we have constructed between ourselves and the earth. Incessant worry, according to this view, is a modern invention. To turn it off, all we need do is turn off the engines and climb down into the countryside. Primitive man, rose-garlanded, slept well.I doubt . . .
Tories urge private cash for NHS
Authors: J. Warden
Journal: BMJ (1998)

Close cooperation with the private health sector to augment the resources of the NHS was advocated at the Conservative party conference in Bournemouth last week by the shadow health secretary, Ann Widdecombe.

In a speech that made a deep impact on demoralised Conservatives, Miss Widdecombe began to map out new Tory thinking which acknowledges that the NHS can no longer meet demand and should harness the wealth of …
Remarks on the Collective Investigation of Disease
Authors: G. M. Humphry
Journal: BMJ (1883)

pend upon whether he begins with amindfor scientific inquiry.I am quite ready to believe, or rather [.would say, I am quite willing to hope that the young men who now enter upon life, and are called quaified practitioners, are really, in the broadest and largest sense, qualified, as well as inthe legal one.Legallythey all are, but some are certainly not qualified to make full use of the knowledge which they may meet with in their career and practice.A very wise old man said that, it would be well if the youngest amongst us would remember that he is not infallible.It is a fault which is apt to prevail, to think that at the conclusion of study and with the right to practice, there is fall power to do all that is required.There is not.Dr. Billings said cleverly the other day that he wished, after thirty yeaxs of practice, he really knew half as much as he was con- vinced he knew when he first obtained his diploma.And I recollect Sir Benjamin Brodie telling me that, when he looked back over forty years of practice, he was astonished, chiefly at the ignorance with which he began; and I think to most of
AIF-1 Is an Actin-Polymerizing and Rac1-Activating Protein That Promotes Vascular Smooth Muscle Cell Migration
Authors: Michael V. Autieri, Sheri E. Kelemen, Karl W. Wendt
Journal: Circulation Research (2003)

Development of vascular restenosis is a multifaceted process characterized by migration and proliferation of vascular smooth muscle cells (VSMCs), resulting in loss of lumen diameter. Characterization of proteins that mediate this process is essential in our understanding of the pathogenesis of arterial injury. Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic, calcium-binding protein that is expressed in VSMCs by allograft and balloon angioplasty injury. AIF-1 is not present in cultured human VSMCs but is induced by cytokines, and overexpression of AIF-1 results in increased VSMC growth and cell-cycle gene expression. To characterize AIF-1 modulatory effects in primary human VSMCs, AIF-1-interacting proteins were identified by an AIF-1/glutathione S transferase fusion protein affinity assay. MALDI-TOF mass spectrophotometric amino analysis identified actin as an AIF-1 interacting protein. This interaction was verified by coimmunoprecipitation. This is a functional interaction, because AIF-1 binds to and polymerizes F-actin in vitro. In unstimulated VSMCs, AIF-1 colocalizes with F-actin but translocates to lamellipodia on stimulation with platelet-derived growth factor. VSMCs stably transduced with AIF-1 retrovirus migrate 2.6-fold more rapidly (85.1+/-2.9 versus 225.5+/-16.6; P<0.001) in response to platelet-derived growth factor versus control cells. AIF-1 colocalizes with Rac1, and AIF-1-transduced VSMCs show a constitutive and enhanced activation of Rac1, providing a mechanism for the increased migration. These data indicate that AIF-1 binds and polymerizes F actin and also regulates Rac1 activity and VSMC migration. Considering the AIF-1 expression pattern in injured arteries, this suggests that AIF-1 may be involved in the cytoskeletal signaling network leading to vascular remodeling.
IL-17 and Th17 Cells
Authors: Thomas Korn, Estelle Bettelli, Mohamed Oukka, Vijay K. Kuchroo
Journal: Annual Review of Immunology (2009)

CD4+ T cells, upon activation and expansion, develop into different T helper cell subsets with different cytokine profiles and distinct effector functions. Until recently, T cells were divided into Th1 or Th2 cells, depending on the cytokines they produce. A third subset of IL-17-producing effector T helper cells, called Th17 cells, has now been discovered and characterized. Here, we summarize the current information on the differentiation and effector functions of the Th17 lineage. Th17 cells produce IL-17, IL-17F, and IL-22, thereby inducing a massive tissue reaction owing to the broad distribution of the IL-17 and IL-22 receptors. Th17 cells also secrete IL-21 to communicate with the cells of the immune system. The differentiation factors (TGF-beta plus IL-6 or IL-21), the growth and stabilization factor (IL-23), and the transcription factors (STAT3, RORgammat, and RORalpha) involved in the development of Th17 cells have just been identified. The participation of TGF-beta in the differentiation of Th17 cells places the Th17 lineage in close relationship with CD4+CD25+Foxp3+ regulatory T cells (Tregs), as TGF-beta also induces differentiation of naive T cells into Foxp3+ Tregs in the peripheral immune compartment. The investigation of the differentiation, effector function, and regulation of Th17 cells has opened up a new framework for understanding T cell differentiation. Furthermore, we now appreciate the importance of Th17 cells in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune disease.
Torula Meningitis in Malaya
Authors: R. W. R. Russell, D. Dean
Journal: BMJ (1957)

Torula Meningitis in MalayaCerebrospinal blastomycosis has been recognized for over 50 years, but is still a rare ocurrence.Only one case has previously been reported in Malaya (Institute of Medical Research, 1953).The following case shows several well- known features of the disease, but is unusual in that it ran a rapid course, death occurring within four weeks of the onset.In addition the presenting symptoms-sudden and complete blindness and deafness-are impressive.
Tumor-Node-Metastasis Staging of Pancreatic Adenocarcinoma
Authors: M. H. G. Katz, R. Hwang, J. B. Fleming, D. B. Evans
Journal: CA A Cancer Journal for Clinicians (2008)

Accurate disease staging of patients with pancreatic cancer is essential to divide patients into prognostic subgroups, to allow delivery of stage-specific therapies, and to facilitate meaningful discussions between physicians and patients regarding management and expected outcomes. The tumor-node-metastasis staging system of the American Joint Commission on Cancer has undergone significant revisions over the past 2 decades. In its current form, the system places an emphasis on preoperative clinical staging and facilitates division of patients with pancreatic cancer into 4 groups based on a determination of local resectability and the presence or absence of distant disease as determined on high-quality cross-sectional imaging. A modern understanding of local tumor factors that influence technical resectability is incorporated into the algorithm. In this review, we examine the American Joint Commission on Cancer staging system, describe the rationale for its use, and demonstrate how it is a clinically relevant tool for the staging and management of patients with pancreatic cancer.
Medical Malpractice in the Military
Authors: Sandeep S. Mangalmurti, Lindsey Murtagh, Michelle M. Mello
Journal: New England Journal of Medicine (2011)

A judicial rule known as the Feres doctrine prohibits military personnel from suing for malpractice. The authors propose policy changes to improve compensation to military personnel injured as a result of malpractice and to promote higher-quality care.
Book: Human Frontiers, Environments and Disease: Past Patterns, Uncertain Futures
Authors: D. Campbell
Journal: BMJ (2001)

Tony McMichael Cambridge University Press, £14.95, pp 413 ISBN 0 521 00494 2 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> The growing public protests that have been punctuating G8 and World Trade Organization meetings remind us that the globalisation of trade and finance is giving rise to ever greater social and economic disparities. There are other challenges associated with ongoing global change. Health inequalities across a wide range of diseases, risks, and consequences suggest cultural, economic, and political causes. … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif