tbuckley/cabot-search huggingface dataset:
Coughing in Laryngectomized Patients
Authors: GIOVANNI A. FONTANA, TITO PANTALEO, FEDERICO LAVORINI, DONATELLA MUTOLO, GIANNI POLLI, MASSIMO PISTOLESI
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Ablation of the larynx implies withdrawal of afferent information from receptors involved both in the control of expiratory flow and in the genesis of protective airway reflexes including coughing. To investigate the effects of laryngectomy on the sensory and motor component of coughing, maximal voluntary cough (MVC) efforts as well as the reflex cough (RC) responses at threshold (T) and suprathreshold (1.8 × T, ST) levels induced by inhalation of progressively increasing concentrations of ultrasonically nebulized distilled water (fog) were analyzed in 10 laryngectomized patients and 10 control subjects. Cough intensity was indexed in terms of both the peak amplitude of the integrated electromyographic activity of abdominal muscles (IEMGp) and the ratio of IEMGp to the duration of the expiratory ramp (Tec), i.e., the rate of rise of IEMG activity (IEMGp/Tec). Cough peak flow was also recorded. Cough threshold was similar in patients and controls, as were IEMGp, Tec, and IEMGp/ Tec recorded during MVC and RCst. In contrast, during RCt, patients' IEMGp was significantly reduced (p < 0.05), thus leading to a significant decrease in IEMGp/Tec (p < 0.05) even in the absence of significant differences in Tec. Cough flow closely correlated with IEMG-related variables. Cough volume acceleration, i.e., the ratio of cough peak flow to the corresponding time to cough peak flow was also significantly reduced in the patients, especially during RCt (p < 0.01). The results suggest that the lack of signals arising from the larynx may result in a reduction of cough volume acceleration as well as in the intensity of abdominal muscle contractions during RCt. These factors may contribute to facilitate the onset and/or the persistence of chest infections in laryngectomized patients. Fontana GA, Pantaleo T, Lavorini F, Mutolo D, Polli G, Pistolesi M. Coughing in laryngectomized patients.
Chronic oral arsenic intoxication as a possible aetiological factor in idiopathic portal hypertension (non-cirrhotic portal fibrosis) in India.
Authors: D V Datta, S K Mitra, P N Chhuttani, R N Chakravarti
Journal: Gut (1979)

Estimates were made of the arsenic concentration in liver specimens from nine patients having idiopathic portal hypertension (IP), and in four livers these were found to be significantly higher than those in patients with cirrhosis and in control subjects. The splenovenogram revealed extensive portosystemic collateral circulation. Corrected sinusoidal pressure and blood flow studies showed higher levels in four patients than in normal subjects. Microscopic examination of liver tissues revealed periportal fibrosis. The higher hepatic arsenic levels that were found were due to the inadvertent drinking of water contaminated with arsenic, adulterated opium, and indigenous medicines. A history of opium intake was not forthcoming but two patients had drunk water contaminated with arsenic and two others had taken bhasams (Ayurvedic medicines prepared by repeated oxidation of ores). Though the aetiology of idiopathic portal hypertension is not known, it is possible that arsenic intake may be one of the factors.
Commentary: Standing up for free speech
Authors: M. O'Donnell
Journal: BMJ (2009)

Critics of the BMJ , and of other medical journals, sometimes complain that editorial decisions are influenced by sinister outsiders. The usual suspects are advertisers, political agencies, and academic oligarchies. Less often named as villains are lobbyists who try to suppress or distort data that might damage their cause and who seek to “silence” editors who publish those data.1

Karl Sabbagh describes a style of lobbying more familiar to journalists working in the national media than to editors and readers of medical journals—the orchestrated harassment of individuals who write or publish articles criticising the Israeli government. The technique has endured for decades because it is effective. Richard Ingrams, editor and columnist, wrote of the historian A J P Taylor, who died in 1990:

“Although [he] was courageously outspoken on many matters, he admitted that in one field he was guilty of journalistic timidity, if not cowardice. ‘Years of experience,’ he wrote, ‘have taught me that one should never venture an opinion on events concerned in any way with Israel or the Jews. Any attempt at a detached view opens the way for letters, telegrams, personal expostulations and above all telephone calls. The only safe course is never, never, to have any opinion about the Middle East.’”

By publishing this paper the BMJ risks yet another bout of hassle. Yet not to have published it would have confirmed that the surest way to silence debate in a medical journal is to organise personal attacks on authors, …
Bcr Kinase Activation by Angiotensin II Inhibits Peroxisome Proliferator-Activated Receptor γ Transcriptional Activity in Vascular Smooth Muscle Cells
Authors: Jeffrey D. Alexis, Nadan Wang, Wenyi Che, Nicole Lerner-Marmarosh, Abha Sahni, Vyacheslav A. Korshunov, Yiping Zou, Bo Ding, Chen Yan, Bradford C. Berk, Jun-ichi Abe
Journal: Circulation Research (2008)

Bcr is a serine/threonine kinase activated by platelet-derived growth factor that is highly expressed in the neointima after vascular injury. Here, we demonstrate that Bcr is an important mediator of angiotensin (Ang) II and platelet-derived growth factor–mediated inflammatory responses in vascular smooth muscle cells (VSMCs). Among transcription factors that might regulate Ang II–mediated inflammatory responses we found that ligand-mediated peroxisome proliferator-activated receptor (PPAR)γ transcriptional activity was significantly decreased by Ang II. Ang II increased Bcr expression and kinase activity. Overexpression of Bcr significantly inhibited PPARγ activity. In contrast, knockdown of Bcr using Bcr small interfering RNA and a dominant-negative form of Bcr (DN-Bcr) reversed Ang II–mediated inhibition of PPARγ activity significantly, suggesting the critical role of Bcr in Ang II–mediated inhibition of PPARγ activity. Point-mutation and in vitro kinase analyses showed that PPARγ was phosphorylated by Bcr at serine 82. Overexpression of wild-type Bcr kinase did not inhibit ligand-mediated PPARγ1 S82A mutant transcriptional activity, indicating that Bcr regulates PPARγ activity via S82 phosphorylation. DN-Bcr and Bcr small interfering RNA inhibited Ang II–mediated nuclear factor κB activation in VSMCs. DN-PPARγ reversed DN-Bcr–mediated inhibition of nuclear factor κB activation, suggesting that PPARγ is downstream from Bcr. Intimal proliferation in low-flow carotid arteries was decreased in Bcr knockout mice compared with wild-type mice, suggesting the critical role of Bcr kinase in VSMC proliferation in vivo, at least in part, via regulating PPARγ/nuclear factor κB transcriptional activity.
Increase in Skeletal Muscle Performance during Emotional Stress in Man
Authors: N. A. BERDINA, O. L. KOLENKO, I. M. KOTZ, A. P. KUZNETZOV, I. M. RODIONOV, A. P. SAVTCHENKO, V. I. THOREVSKY
Journal: Circulation Research (1972)

An emotional stress arising as a result of intense mental arithmetic causes (in most subjects) an increase in blood flow through resting forearm muscle by an average of 85%. Combination of voluntary sustained handgrip contraction with mental arithmetic has shown that the duration of contraction increases by an average of 46%. This effect appears only in subjects who display an increase in blood flow as a result of mental arithmetic. A rise in muscle performance is also observed during mental arithmetic when contraction of forearm muscle is caused by direct stimulation of the motor nerve in the upper arm. Intra-arterial injection of atropine sharply reduces both the increase in blood flow through the resting muscle and the increase in muscle performance associated with mental arithmetic. Control performance (without mental arithmetic) is not altered by administration of atropine. Analysis of blood flow during muscle contraction leads to the conclusion that an increase in muscle performance during emotional stress is not dependent on an increase in muscle blood flow. The data suggest that during emotional stress the sympathetic nervous system causes metabolic changes in skeletal muscles that lead to an increase in muscle performance when oxygen deficiency exists.
THE COMPARATIVE EFFECTS OF VITAMIN B1 DEFICIENCY AND RESTRICTION OF FOOD INTAKE ON THE RESPONSE OF MICE TO THE LANSING STRAIN OF POLIOMYELITIS VIRUS, AS DETERMINED BY THE PAIRED FEEDING TECHNIQUE
Authors: Claire Foster, James H. Jones, Werner Henle, Frieda Dorfman
Journal: The Journal of Experimental Medicine (1944)

In a paired feeding experiment the effects of vitamin B(1) deficiency and of restriction of food intake have been compared. In both groups of animals the number of cases of paralysis and the number of deaths were less than in a control group on an unrestricted amount of the complete diet. The maximum difference occurred on the 15th day after inoculation. The incidence of paralysis and death in the vitamin-deficient group was also less than in the paired restricted group. The maximum difference occurred on the 17th day following inoculation, after which the difference gradually became less. At the end of the experiment (28 days) there was a slightly greater number of deaths in the restricted group than in the vitamin-deficient group. Apparently the effect of vitamin B(1) deficiency on the action of the virus of poliomyelitis in the mouse is not due solely to the resulting anorexia. From the 3rd to the 25th day after inoculation the animals were examined at hourly intervals throughout the day and night. On the 26th and 27th days they were examined every 3 hours. Except for two mice in the unrestricted group dying before the hourly examinations were begun, peripheral paralysis was observed in every animal which died.
Assessment of rheumatoid activity based on clinical features and blood and synovial fluid analysis.
Authors: M Farr, M J Kendall, D W Young, M J Meynell, C F Hawkins
Journal: Annals of the Rheumatic Diseases (1976)

Joint inflammation in rheumatoid arthritis has been assessed, and the most useful guides to disease activity were determined by analysis of synovial fluid and blood together with the history of joint disability. The patient's own evaluation of the amount of pain suffered was the most useful clinical assessment. Differential cell count and glucose estimations were the most helpful guides in the synovial fluid, while C-reactive protein in the serum most accurately reflected disease activity. The effects of systemic steroids on these indices were studied, and the differences between seronegative and seropositive patients noted.
Patients with Slowly Proliferative Early Breast Cancer Have Low Five-Year Recurrence Rates in a Phase III Adjuvant Trial of Capecitabine
Authors: Joyce O'Shaughnessy, Hartmut Koeppen, Yuanyuan Xiao, Mark R. Lackner, Devchand Paul, Christopher Stokoe, John Pippen, Lea Krekow, Frankie Ann Holmes, Svetislava Vukelja, Deborah Lindquist, Scot Sedlacek, Ragene Rivera, Robert Brooks, Kristi McIntyre, Carrie Brownstein, Silke Hoersch, Joanne L. Blum, Stephen Jones
Journal: Clinical Cancer Research (2015)

We conducted a randomized phase III study to determine whether patients with early breast cancer would benefit from the addition of capecitabine (X) to a standard regimen of doxorubicin (A) plus cyclophosphamide (C) followed by docetaxel (T).Treatment comprised eight cycles of AC→T (T dose: 100 mg/m(2) on day 1) or AC→XT (X dose: 825 mg/m(2) twice daily, days 1-14; T dose: 75 mg/m(2) on day 1). The primary endpoint was 5-year disease-free survival (DFS).Of 2,611 women, 1,304 were randomly assigned to receive AC→T and 1,307 to receive AC→XT. After a median follow-up of 5 years, the study failed to meet its primary endpoint [HR, 0.84; 95% confidence interval (CI), 0.67-1.05; P = 0.125]. A significant improvement in overall survival, a secondary endpoint, was seen with AC→XT versus AC→T (HR, 0.68; 95% CI, 0.51-0.92; P = 0.011). There were no unexpected adverse events. Of patients with estrogen receptor (ER)-positive/HER2-negative disease, 70% of whom were node-positive, 26% and 59% had tumors with a centrally assessed Ki-67 score of <10% or <20%, respectively, and only 17 (2%) and 53 (6%) DFS events, respectively, occurred in these groups at 7 years.The very low event rate in patients with ER-positive, low Ki-67 cancers, regardless of nodal status, strongly suggests that these patients should not be enrolled in adjuvant trials that assess 5-year DFS rates and that central Ki-67 analyses can identify these patients.
Code of Ethics.
Authors: John Wright
Journal: JAMA (1893)

<h3>To the Editor of The Journal of the American Medical Association.</h3><h3>Dear Sir:</h3> —The " Code" question it appears is not yet settled. I have read with care everything that I have seen in print on both sides of the question and I must confess that I have not seen a single convincing argument that the Code should be abolished or materially changed or amended. There have been many harsh and positive assertions that the Code is an awful document, that its language is bad, that it is old and that it does great injustice to somebody, and many other similar expressions, but such declarations are not arguments, and what these fellows want I do not believe any one can tell; one will assert that the Code is old and therefore it should be abolished and another will assert that the Code never has been enforced and never can be, and
Firearm Violence and Public Health
Authors: Karl P. Adler
Journal: JAMA (1994)

FIREARM violence has reached epidemic proportions in this country and is now a public health emergency, accounting for one fifth of all injury deaths in the United States and second only to motor vehicles as a cause of fatal injury.<sup>1</sup>In addition, for every fatal injury, an estimated seven nonfatal injuries occur.<sup>2</sup>Further, firearm-related injuries imposed an estimated $19 billion economic burden on the United States in 1990 in addition to the direct health care costs.<sup>3</sup>If firearm violence continues to increase, it is expected that by the year 2003, the number of deaths from firearms will surpass the number of deaths caused by motor vehicles, and firearms will become this country's leading cause of injury-related death.<sup>4</sup> The burden of firearm violence is borne to a considerable degree by our country's most vulnerable population—its young people. Homicide is the leading cause of death for young black
Proteasome inhibition reduces superantigen-mediated T cell activation and the severity of psoriasis in a SCID-hu model
Authors: Thomas M. Zollner, Maurizio Podda, Christine Pien, Peter J. Elliott, Roland Kaufmann, Wolf-Henning Boehncke
Journal: Journal of Clinical Investigation (2002)

There is increasing evidence that bacterial superantigens contribute to inflammation and T cell responses in psoriasis. Psoriatic inflammation entails a complex series of inductive and effector processes that require the regulated expression of various proinflammatory genes, many of which require NF-κB for maximal trans-activation. PS-519 is a potent and selective proteasome inhibitor based upon the naturally occurring compound lactacystin, which inhibits NF-κB activation by blocking the degradation of its inhibitory protein IκB. We report that proteasome inhibition by PS-519 reduces superantigen-mediated T cell–activation in vitro and in vivo. Proliferation was inhibited along with the expression of very early (CD69), early (CD25), and late T cell (HLA-DR) activation molecules. Moreover, expression of E-selectin ligands relevant to dermal T cell homing was reduced, as was E-selectin binding in vitro. Finally, PS-519 proved to be therapeutically effective in a SCID-hu xenogeneic psoriasis transplantation model. We conclude that inhibition of the proteasome, e.g., by PS-519, is a promising means to treat T cell–mediated disorders such as psoriasis.
GENETIC CONTROL OF THE IMMUNE RESPONSE
Authors: Peter Lonai, Hugh O. McDevitt
Journal: The Journal of Experimental Medicine (1974)

In vitro antigen-induced tritiated thymidine uptake has been used to study the response of sensitized lymphocytes to (T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L in responder and nonresponder strains of mice. The reaction is T-cell and macrophage dependent. Highly purified T cells (91% Thy 1.2 positive) are also responsive, suggesting that this in vitro lymphocyte transformation system is not B-cell dependent. Lymphocytes from high and low responder mice stimulated in vitro react as responders and nonresponders in a pattern identical to that seen with in vivo immunization. Stimulation occurs only if soluble antigen is added at physiological temperatures; antigen exposure at 4 degrees C followed by washing and incubation at 37 degrees C fails to induce lymphocyte transformation. Stimulation is specific for the immunizing antigen and does not exhibit the serologic cross-reactivity which is characteristic of these three antigens and their respective antisera. The reaction can be inhibited by anti-H-2 sera but not by anti-immunoglobulin sera. The anti-immunoglobulin sera did, however, inhibit lipopolysaccharide or pokeweed mitogen stimulation. These results suggest that the Ir-1A gene(s) are expressed in T cells, and that there are fundamental physiologic differences between T- and B-cell antigen recognition.
Feasibility of Repairing Glomerular Basement Membrane Defects in Alport Syndrome
Authors: Xiaobo Lin, Jung Hee Suh, Gloriosa Go, Jeffrey H. Miner
Journal: Journal of the American Society of Nephrology (2013)

Alport syndrome is a hereditary glomerular disease that leads to kidney failure. It is caused by mutations affecting one of three chains of the collagen α3α4α5(IV) heterotrimer, which forms the major collagen IV network of the glomerular basement membrane (GBM). In the absence of the α3α4α5(IV) network, the α1α1α2(IV) network substitutes, but it is insufficient to maintain normal kidney function. Inhibition of angiotensin-converting enzyme slows progression to kidney failure in patients with Alport syndrome but is not a cure. Restoration of the normal collagen α3α4α5(IV) network in the GBM, by either cell- or gene-based therapy, is an attractive and logical approach toward a cure, but whether or not the abnormal GBM can be repaired once it has formed and is functioning is unknown. Using a mouse model of Alport syndrome and an inducible transgene system, we found that secretion of α3α4α5(IV) heterotrimers by podocytes into a preformed, abnormal, filtering Alport GBM is effective at restoring the missing collagen IV network, slowing kidney disease progression, and extending life span. This proof-of-principle study demonstrates the plasticity of the mature GBM and validates the pursuit of therapeutic approaches aimed at normalizing the GBM to prolong kidney function.
First-Line Crizotinib versus Chemotherapy in <i>ALK</i>-Positive Lung Cancer
Authors: Benjamin J. Solomon, Tony Mok, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Tarek Mekhail, Enriqueta Felip, Federico Cappuzzo, Jolanda Paolini, Tiziana Usari, Shrividya Iyer, Arlene Reisman, Keith D. Wilner, Jennifer Tursi, Fiona Blackhall
Journal: New England Journal of Medicine (2014)

The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown.We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression-free survival as assessed by independent radiologic review.Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates were 74% and 45%, respectively (P<0.001). Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P=0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life.Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer; PROFILE 1014 ClinicalTrials.gov number, NCT01154140.).
Breast feeding, but not use of oral contraceptives, is associated with a reduced risk of rheumatoid arthritis
Authors: M Pikwer, U Bergström, J-Å Nilsson, L Jacobsson, G Berglund, C Turesson
Journal: Annals of the Rheumatic Diseases (2008)

Objective: To determine whether breast feeding or the use of oral contraceptives (OCs) affects the future risk of rheumatoid arthritis (RA) in a community-based prospective cohort. Methods: A community-based health survey (18 326 women) was linked to regional and national registers, and incident cases of RA were identified. All women with a diagnosis of RA after inclusion in the health survey (n = 136) and four female controls for every case, who were alive and free from RA when the index person was given a diagnosis of RA, were included in a case–control study. Data on lifestyle factors at baseline were derived from a self-administered questionnaire. Potential predictors were examined in logistic regression models. Results: 136 women with incident RA were compared with 544 age-matched controls. A longer history of breast feeding was associated with a reduced risk of RA (OR 0.46 (95% CI 0.24 to 0.91) for women who had breast fed for ⩾13 months and OR 0.74 (95% CI 0.45 to 1.20) for those who had breast fed for 1–12 months, compared with those who had never breast fed). The protective effect of longer breast feeding remained significant after adjustment for smoking and level of education in multivariate models, and point estimates were protective also when the analyses were restricted to parous women. Neither parity nor OC use had any significant effect on the risk of RA. Conclusion: In this study, long-term breast feeding, but not OC use, was associated with a significant reduction in the risk of RA.