tbuckley/cabot-search huggingface dataset:
Swan song for the Swan-Ganz catheter?
Authors: N. Soni
Journal: BMJ (1996)

An American study published earlier this month has shown that the use of a pulmonary artery catheter is associated with increased mortality in a wide range of conditions, including many of the accepted indications for using a catheter.1 Is this finding unexpected—and what should we do about it?

Connors et al retrospectively reviewed 5735 critically ill patients with one of nine prespecified disease categories treated in 1989-94. They assessed the severity of illness in all patients and compared the outcome in those who received and those who did not receive a pulmonary artery catheter within the first 24 hours of care. The patients receiving a pulmonary artery catheter had higher APACHE III scores and lower predicted survival at two months. They also had higher mortality, length of stay, and financial costs. To compare with those who did not receive a pulmonary artery catheter, propensity scores (a new statistical method) were used to adjust for treatment selection. The results strongly suggest that in all groups mortality, the length of intensive care, and hospital costs were higher when a pulmonary catheter was used. Catheters seemed to have the highest associated risk in postoperative patients and those who were not severely ill. …
Educational-Debt Relief for Clinical Investigators — A Vote of Confidence
Authors: David G Nathan
Journal: New England Journal of Medicine (2002)

Programs of educational-debt relief sponsored by the National Institutes of Health (NIH) have recently been enacted as a means of recruiting and retaining clinical investigators who perform patient-oriented research. Should these programs be extended immediately to include all physician-scientists? I am opposed to this suggestion, and my reasons follow.BackgroundOn November 13, 2000, then-President Bill Clinton signed the Public Health Improvement Act. The document contains the Clinical Research Enhancement Act, which includes provisions for the alleviation of the educational debt of nascent clinical investigators participating in the NIH extramural program.1 The proposed rules that would govern implementation of the . . .
THE MANAGEMENT OF SOME COMPLICATIONS FOLLOWING ABDOMINAL OPERATIONS
Authors: FRANK H. LAHEY
Journal: JAMA (1927)

Unexpected and, as a rule, preventable postoperative complications make up a large part of the mortality which follows deliberate operative procedures on persons in good general health and presumed to be reasonable surgical risks. These complications are at least in a considerable measure avoidable and, having arisen, assume serious aspects in proportion to the lateness with which they are discovered and adequately treated. Perhaps the simplest and least fatal but most annoying postoperative complication is wound infection, particularly in the clean undrained wounds. Explanations of postoperative fevers without obvious cause should be first sought in the wound itself, and in a large number of cases will be found to be due to localized accumulations, many of which can be cared for by early drainage without further involvement of the wound. A method which I have successfully employed to discover these small localized inflammatory areas early is, with sterile precautions, to
Effects of Long-term Smoking on Myocardial Blood Flow, Coronary Vasomotion, and Vasodilator Capacity
Authors: Roxana Campisi, Johannes Czernin, Heiko Schöder, James W. Sayre, Fernando D. Marengo, Michael E. Phelps, Heinrich R. Schelbert
Journal: Circulation (1998)

Background —The effect of long-term smoking on coronary vasomotion and vasodilator capacity in healthy smokers is unknown. Methods and Results —Myocardial blood flow (MBF) was quantified with [ 13 N]ammonia and positron emission tomography (PET) at rest, during cold pressor testing (endothelium-dependent vasomotion), and during dipyridamole-induced hyperemia in 16 long-term smokers and 17 nonsmokers. MBF at rest did not differ between the 2 groups. Cold induced similar increases in rate-pressure product (RPP) in smokers and nonsmokers. However, MBF increased only in nonsmokers and was, during cold, higher than in smokers (0.91±0.18 versus 0.78±0.14 mL · g −1 · min −1 , P &lt;0.05). MBF normalized to the RPP (derived from the ratio of MBF ([milliliters per gram per minute] to RPP [beats per minute times millimeters of mercury] times 10 000) declined in smokers but remained unchanged in nonsmokers (0.86±0.10 versus 0.72±0.11, P =0.0006, and 0.99±0.25 versus 0.96±0.27, P =NS). The hyperemic response to dipyridamole and the myocardial flow reserve did not differ between the 2 groups. In a multiple regression model adjusted for age, sex, serum lipid levels, years of smoking, and pack-years, years of smoking was the strongest predictor of the normalized blood flow response to cold ( P &lt;0.001), followed by the HDL/LDL ratio. Conclusions —The normal hyperemic response to dipyridamole in long-term smokers indicates a preserved endothelium-independent coronary vascular smooth muscle relaxation, whereas the abnormal response to cold suggests a defect in coronary vasomotion likely located at the level of the coronary endothelium. Its severity depends on the total exposure time to smoking.
Health-Related Quality of Life and Utility in Patients with Advanced Non–Small-Cell Lung Cancer: A Prospective Cross-Sectional Patient Survey in a Real-World Setting
Authors: Christos Chouaid, Jason Agulnik, Erdem Goker, Gerarda J.M. Herder, Jason F. Lester, Johann Vansteenkiste, Henrik W. Finnern, Juliane Lungershausen, Jennifer Eriksson, Kun Kim, Paul L.R. Mitchell
Journal: Journal of Thoracic Oncology (2013)

Non-small-cell lung cancer (NSCLC) has a significant impact on patients' health-related quality of life (HRQOL). This study aimed to measure health state utility values representing the individual's preferences for specific health-related outcomes in advanced NSCLC patients and to assess predictive parameters.We conducted a prospective quality-of-life survey on advanced NSCLC patients in 25 hospitals in Europe, Canada, Australia, and Turkey. HRQOL was assessed using the EuroQol (EQ-5D) questionnaire and EQ-5D utility and EQ-visual analog (EQ-VAS) scores were estimated.Three hundred nineteen patients were recruited of which 263 had evaluable data. Mean utility for progression-free (PF) patients on first-, second-, and third-/fourth-line treatment was 0.71 (SD = 0.24), 0.74 (SD = 0.18), and 0.62 (SD = 0.29), respectively. Mean utility for patients with progressive disease (PD) while on first-, second- and third-/fourth-line treatment was 0.67 (SD = 0.2), 0.59 (SD = 0.34), and 0.46 (SD = 0.38), respectively. Overall, patients with PD had lower mean utility scores than PF patients (0.58 versus 0.70). The results of the EQ-VAS showed that the score decreased with later treatment lines. Patients with PD had a 10-point decrease in VAS scores compared with PF patients (53.7 versus 66.6). The regression analysis revealed that stage IV disease, higher lines of treatment, and health state were significant predictors of utility at the 10% level.The results presented indicate a substantial impact of lung cancer on patients' HRQOL, with stage IV disease, line of treatment, and PD, resulting in considerable deterioration of utility. The values obtained here will inform evaluations of cost-utility for NSCLC therapies.
The anatomical substrates of wolff-parkinson-white syndrome. A clinicopathologic correlation in seven patients.
Authors: A E Becker, R H Anderson, D Durrer, H J Wellens
Journal: Circulation (1978)

Clinicopathological correlations were made on the hearts from seven patients known to have exhibited electrocardiographic evidence of the Wolff-Parkinson-White syndrome. In each case, clinical and pathological investigations were conducted independently, neither group of investigators having knowledge of the other's results. In all seven hearts, the entire atrioventricular junctions were serially sectioned. Accessory atrioventricular connections were predicted in all seven cases following electrocardiographic investigation. Connections were identified histopathologically in four hearts in the predicted site. In another case two connections were identified, one being considered responsible for the pre-excitation. In the sixth case a right lateral connection was anticipated, but only accessory nodo-ventricular fibers were identified following histopathologic studies. In the final case, a posterior septal connection was predicted but the entire septum had fibrosed following previous operation. These findings are discussed in the light of the investigative techniques used, the theories of pre-excitation and the embryogenetic mechanisms producing accessory atrioventricular connections.
Doctors are key to securing the UK's first conviction for female genital mutilation, say campaigners
Authors: S. Hives-Wood
Journal: BMJ (2013)

Doctors who find evidence of female genital mutilation (FGM) should treat it as a crime and report it to police, a coalition of health organisations has recommended.

The coalition said that a government funded awareness strategy was needed, similar to that launched in the 1990s to tackle HIV, to prevent the genital mutilation of young girls. Doctors and other health and care professionals should be held responsible for monitoring female genital mutilation and treating it as child abuse. 

Female genital mutilation has been illegal in the United Kingdom since 1985, but there have been no prosecutions for it to date. The campaigners said that taking an aggressive multiagency and multiprofessional approach to identifying cases of female …
Letter: Effect of levodopa on tremor in Benedikt's syndrome.
Authors: T Fujieda, T Yamauchi, S Takahashi, T Moroji
Journal: BMJ (1974)

serotonin in the striatum.In the light of these findings and our present clinical finding it seems reasonable to conclude that mid- brain tremor is most probably due to combined interruption of the cerebellofugal pathway, the rubrospinal tract, and the ascending monoaminergic nervous pathways.-Weare, etc.,
Moderate Pulmonary Arterial Hypertension in Male Mice Lacking the Vasoactive Intestinal Peptide Gene
Authors: Sami I. Said, Sayyed A. Hamidi, Kathleen G. Dickman, Anthony M. Szema, Sergey Lyubsky, Richard Z. Lin, Ya-Ping Jiang, John J. Chen, James A. Waschek, Smadar Kort
Journal: Circulation (2007)

Background— Vasoactive intestinal peptide (VIP), a pulmonary vasodilator and inhibitor of vascular smooth muscle proliferation, has been reported absent in pulmonary arteries from patients with idiopathic pulmonary arterial hypertension (PAH). We have tested the hypothesis that targeted deletion of the VIP gene may lead to PAH with pulmonary vascular remodeling. Methods and Results— We examined VIP knockout (VIP −/− ) mice for evidence of PAH, right ventricular (RV) hypertrophy, and pulmonary vascular remodeling. Relative to wild-type control mice, VIP −/− mice showed moderate RV hypertension, RV hypertrophy confirmed by increased ratio of RV to left ventricle plus septum weight, and enlarged, thickened pulmonary artery and smaller branches with increased muscularization and narrowed lumen. Lung sections also showed perivascular inflammatory cell infiltrates. No systemic hypertension and no arterial hypoxemia existed to explain the PAH. The condition was associated with increased mortality. Both the vascular remodeling and RV remodeling were attenuated after a 4-week treatment with VIP. Conclusions— Deletion of the VIP gene leads to spontaneous expression of moderately severe PAH in mice during air breathing. Although not an exact model of idiopathic PAH, the VIP −/− mouse should be useful for studying molecular mechanisms of PAH and evaluating potential therapeutic agents. VIP replacement therapy holds promise for the treatment of PAH, and mutations of the VIP gene may be a factor in the pathogenesis of idiopathic PAH.
Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease
Authors: John D. Belcher, Chunsheng Chen, Julia Nguyen, Liming Milbauer, Fuad Abdulla, Abdu I. Alayash, Ann Smith, Karl A. Nath, Robert P. Hebbel, Gregory M. Vercellotti
Journal: Blood (2013)
Large Errors in the Dosing of Medications for Children
Authors: Eran Kozer, Dennis Scolnik, Tara Keays, Kevin Shi, Tracy Luk, Gideon Koren
Journal: New England Journal of Medicine (2002)

To the Editor: Dosing errors are among the most common types of medication errors.1–3 Errors by a factor of 10 (the administration of a dose 10 times or 1/10 as high as appropriate) are of particul...
Value of Transfusion.
Authors: Frederick P. Henry
Journal: JAMA (1899)

Philadelphia, Pa., Jan. 2, 1899. <h3>To the Editor:</h3> —In the course of an interesting editorial on the "Value of Transfusion," in theJournal, Dec. 31, 1898, the operation is suggested in typhoid fever and other toxic conditions, and the statement is made that there is no literature at hand: i.e., presumably, no record, of the measure having been resorted to in the treatment of typhoid. In Volkmann's<i>Sammlung klinischer Vorträge</i>(No. 11, 1890), Hermann Sahli gives an account of two cases of typhoid fever in which he injected, beneath the skin of the abdomen and elsewhere, as much as a liter of a saline solution. In a footnote in the course of my article on typhoid fever, in the "System of Practical Therapeutics," edited by Prof. H. A. Hare (vol. ii, p. 290), I briefly referred to Sahli's work and have also mentioned the fact that I have treated, at
Anti-tumor activity of obinutuzumab and rituximab in a follicular lymphoma 3D model
Authors: E Decaup, C Jean, C Laurent, P Gravelle, S Fruchon, F Capilla, A Marrot, T Al Saati, F-X Frenois, G Laurent, C Klein, N Varoqueaux, A Savina, J-J Fournié, C Bezombes
Journal: Blood Cancer Journal (2013)

Follicular lymphomas (FLs) account for 35-40% of all adult lymphomas. Treatment typically involves chemotherapy combined with the anti-CD20 monoclonal antibody (MAb) rituximab (RTX). The development of the type II anti-CD20 MAb obinutuzumab (GA101) aims to further improve treatment. Here, using FL cells we show that RTX and GA101 display a similar activity on RL cells cultured in 2D. However, 2D culture cannot mimic tumor spatial organization and conventional 2D models may not reflect the effects of antibodies as they occur in vivo. Thus, we created a non-Hodgkin's lymphoma (NHL) 3D culture system, termed multicellular aggregates of lymphoma cells (MALC), and used it to compare RTX and GA101 activity. Our results show that both antibodies display greater activity towards FL cells in 3D culture compared with 2D culture. Moreover, we observed that in the 3D model GA101 was more effective than RTX both in inhibiting MALC growth through induction of (lysosomal) cell death and senescence and in inhibiting intracellular signaling pathways, such as mammalian target of rapamycin, Akt, PLCgamma (Phospholipase C gamma) and Syk. Altogether, our study demonstrates that spatial organization strongly influences the response to antibody treatment, supporting the use of 3D models for the testing of therapeutic agents in NHL.
FATAL APLASTIC ANEMIA FOLLOWING QUINACRINE THERAPY IN CHRONIC DISCOID LUPUS ERYTHEMATOSUS
Authors: Leo G. Parmer
Journal: JAMA (1953)

The use of quinacrine (Atabrine) has declined considerably since the introduction of newer antimalarials. However, recent new indications for the drug have revived its use. Page reported on the treatment in 18 cases of chronic discoid lupus erythematosus with quinacrine with striking results. Only one patient failed to improve considerably, and in a few cases all the lesions completely disappeared within six weeks of the start of treatment. In two patients associated changes of rheumatoid arthritis disappeared as the skin condition improved. This latter finding was extended by Freedman and Bach, who treated 23 arthritic patients with quinacrine, of whom all but one were said to have improved. Pain subsided, soft tissue swelling decreased, and movement became free and more vigorous. Six to 10 weeks of therapy were necessary before all signs of joint inflammation disappeared. In this series only one side-reaction, a macular eruption, developed in a patient who
Antibody to VLA-4, but not to L-selectin, protects neuronal M2 muscarinic receptors in antigen-challenged guinea pig airways.
Authors: A D Fryer, R W Costello, B L Yost, R R Lobb, T F Tedder, D A Steeber, B S Bochner
Journal: Journal of Clinical Investigation (1997)

Antigen challenge of sensitized guinea pigs decreases the function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lung, potentiating vagally induced bronchoconstriction. Loss of M2 receptor function is associated with the accumulation of eosinophils around airway nerves. To determine whether recruitment of eosinophils via expression of VLA-4 and L-selectin is critical for loss of M2 receptor function, guinea pigs were pretreated with monoclonal antibodies to VLA-4 (HP1/2) or L-selectin (LAM1-116). Guinea pigs were sensitized and challenged with ovalbumin, and M2 receptor function was tested. In controls, blockade of neuronal M2 muscarinic receptors by gallamine potentiated vagally induced bronchoconstriction, while in challenged animals this effect was markedly reduced, confirming M2 receptor dysfunction. Pretreatment with HP1/2, but not with LAM1-116, protected M2 receptor function in the antigen-challenged animals. HP1/2 also inhibited the development of hyperresponsiveness, and selectively inhibited accumulation of eosinophils in the lungs as measured by lavage and histology. Thus, inhibition of eosinophil influx into the lungs protects the function of M2 muscarinic receptors, and in so doing, prevents hyperresponsiveness in antigen-challenged guinea pigs.
Ig-specific T cell receptor-transgenic T cells are not deleted in the thymus and are functional in vivo.
Authors: F Granucci, M Rescigno, G Marconi, M Foti, P Ricciardi-Castagnoli
Journal: The Journal of Experimental Medicine (1996)

The mechanisms that induce T cell tolerance to circulating self-proteins are still controversial, and both the deletion and selection of autoreactive T cells have been observed in the thymus of transgenic mouse models. To address the question of the induction of tolerance to circulating self-constituents, a T cell receptor-transgenic mouse specific for the serum protein immunoglobulin (Ig) gamma and (IgG2ab) was generated. The choice of an allotype-specific T cell also allowed the generation of transgenic control mice not expressing the self-antigen. It was found that the transgenic T cells were not deleted in the thymus, did not become tolerant in the periphery, and regulated the function of gamma 2ab-positive B cells as shown by the lack of IgG2ab protein in the serum of the transgenic mice. In spite of this activity in vivo, the transgenic T cells did not proliferate in vitro in response to the allotype-specific peptide. Interestingly, antigen-specific T cell proliferation could be restored if the transgenic mice were previously challenged to induce IgG2ab responses. After this challenge, IgG2ab protein in the serum of the transgenic mice could be partially restored, although still remaining much lower than in control mice. In addition, there was a dramatic increase in serum IgE levels, suggesting that newly generated gamma 2ab-secreting B cells can be induced to switch to IgE in the presence of allotype-specific T cells. These results indicate that Ig-specific T cells may represent a late-acting form of T cell help for the regulation of the IgG2a-to-IgE class switch.
Abstract 3320: Functional RANK expression is observed in disaggregated primary human lung tumors
Authors: John M. Rossi, Yang Pan, William C. Dougall, Daniel Branstetter, Allison Jacob, Jude Canon, Robert D. Loberg
Journal: Cancer Research (2014)

Abstract The receptor activator of nuclear factor-κβ (RANK) and its ligand RANKL play a key role in the regulation of bone remodeling. RANK pathway activation has also been implicated in various aspects of lung tumor biology. In mouse models of NSCLC bone metastasis, RANKL inhibition led to decreased skeletal tumor progression and increased survival. By IHC, RANK expression has been reported to occur in approximately 60-70% of NSCLC cases profiled. Expression and function have been observed using human lung cancer cell line models. However, there is a lack of understanding with respect to the role RANK signaling plays in primary human lung tumor cells. To better understand RANK biology in lung cancer a novel platform was employed to measure RANK expression and pathway response to RANKL stimulation in freshly resected human lung tumors. RANK expression and function were investigated in viable, non-apoptotic disaggregated primary NSCLC samples by flow cytometry using previously described methodology. Cell surface RANK expression was evaluated using a monoclonal antibody (N2B10, Amgen). Evidence of receptor function was investigated by analysis of relevant intracellular signaling pathways using phospho-specific antibodies following ex vivo RANKL stimulation (2.5 pM - 5 µg/mL, 30 minutes). A cocktail of EGF, HGF and IGF1 was also employed as a positive control for functional pathway activation. Molecular profiling of somatic mutations is ongoing to further elucidate the molecular characteristics of tumors that have functional RANK signaling. Table 1 summarizes RANK expression and RANKL response profiles. This study demonstrates that RANK is expressed and functional in a subset of primary human lung tumors. Data presented here confirms RANK expression on tumor cells of NSCLC and suggests that RANK pathway utilization is restricted to the sub-set of tumors that express detectable RANK. Table 1SquamousAdenocarcinomaOther# Samples12217RANK Positive373NFκβ p65 Response1pAKT Response1pERK Response2p38 Responsep65 + pAKT Response1p38 + pERK Response1p65 + p38 + pAKT Response1% Responder (Total*)17%19%14%% Responder (RANK positive*)67%57%33%% Responder (EGF/ HGF/ IGF1)75%95%86%Other: large cell (1), carcinoid (1), adenosquamous (3), neuroendocrine (2)*Within Histology subtype Citation Format: John M. Rossi, Yang Pan, William C. Dougall, Daniel Branstetter, Allison Jacob, Jude Canon, Robert D. Loberg. Functional RANK expression is observed in disaggregated primary human lung tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3320. doi:10.1158/1538-7445.AM2014-3320