tbuckley/cabot-search huggingface dataset:
The Application of Preventive Medicine to the Control of Violence
Authors: Stuart P. Weisberg, Eric P. Wilkinson
Journal: JAMA (2000)

THE EVOLUtion of Modern Medicine, discussed with great optimism the emergence of preventive medicine.He marveled at the successful public health campaigns against malaria and yellow fever that decreased morbidity and mortality by "up to an order of magnitude". 1 Since early in the last century, scientific data have correlated clinical illness with social behaviors and public health advocates have pursued safety legislation.Most recently, public health measures have legally obligated drivers to fasten their seatbelts and severely restricted smoking.Physicians have now begun to look more closely at another social factor leading to significant clinical morbidity: violence.Recent research has changed our perception of violence.In 1985, William Foege, then Executive Director, The Task Force for Child Survival and Development, noted that violence was largely viewed as a law enforcement or welfare problem until the early 1980s. 2 A recent literature review tallied the most common types of violence discussed in the public health context.Youth and gang violence, gun violence, and domestic violence topped the list.A third of the reviewed articles justified the role of public health in preventing violence by arguing that violence is a pervasive threat. 3 This argument invokes one of preventive medicine's main tenets: to prevent population exposures that can inflict injury and death.The articles in this issue explore the myriad ways in which violence results in injury and death.Salmaan Keshavjee and Mercedes Becerra link the current tuberculosis epidemic in Tajikistan to the country's civil war and separation from Russia.Sheri Fink describes the conflicts of interest faced by humanitarian aid physicians trying to mitigate the violence in the war in Kosovo.Howard Spivak, Katherine Christoffel, and Martha Witwer discuss the tragic consequences of youth violence in the United States from clinical and epidemiological perspectives.Brian Phelps addresses physicians' failure to properly screen patients for domestic violence.The authors clearly envision violence as the disease, but how can such a disease be cured?Preventive medicine transformed the role of the physician from individual healer to caretaker for the public's health.Osler calumniated society's failure to enact preventive health measures against the unsanitary conditions conducive to typhus. 1 But a mere bacterium causes typhus, while complex and deeply entrenched societal and governmental attitudes, such as fear of and hostility toward ethnic groups and the right of citizens to bear arms, contribute to violence and its terrible sequelae.Such causative agents have proved far harder to dismantle than a simple package of protoplasm.Osler listed the tools of preventive medicine in his 1913 lecture-"education, organization, cooperation." 1 Perhaps information in the following articles will help hone them against violence.
Cimetidine Toxic Reactions Masquerading as Delirium Tremens
Authors: William W. Weddington
Journal: JAMA (1981)

CIMETIDINE, an inhibitor of gastric acid secretion, is widely used for the treatment of peptic ulcer and to prevent gastrointestinal (GI) bleeding in high-risk patients. Infrequent side effects of cimetidine include headache, dizziness, fatigue, rash, diarrhea, constipation, muscle pain, gynecomastia, and granulocytopenia.<sup>1,2</sup> Grimson<sup>3</sup>reported two cases of mental confusion after patients received double dosages. Subsequently, other case reports<sup>4-6</sup>described cimetidine-associated confusion, delirium, depression, and coma. We describe a patient in whom a cimetidine-associated delirium developed that initially was thought to be alcohol withdrawal. Subsequent treatment of presumed delirium tremens led to a worsened clinical state. <h3>Report of a Case</h3> A 64-year-old woman was admitted to a hospital for upper abdominal pain. She had a history of drinking several beers each day, but her blood alcohol level was 0 mg/dL at admission. A nasogastric aspirate was guiac positive, and a spot urine amylase was positive. Her BUN and
A Six-Gene Signature Predicting Breast Cancer Lung Metastasis
Authors: Thomas Landemaine, Amanda Jackson, Akeila Bellahcène, Nadia Rucci, Soraya Sin, Berta Martin Abad, Angels Sierra, Alain Boudinet, Jean-Marc Guinebretière, Enrico Ricevuto, Catherine Noguès, Marianne Briffod, Ivan Bièche, Pascal Cherel, Teresa Garcia, Vincent Castronovo, Anna Teti, Rosette Lidereau, Keltouma Driouch
Journal: Cancer Research (2008)

Abstract The lungs are a frequent target of metastatic breast cancer cells, but the underlying molecular mechanisms are unclear. All existing data were obtained either using statistical association between gene expression measurements found in primary tumors and clinical outcome, or using experimentally derived signatures from mouse tumor models. Here, we describe a distinct approach that consists of using tissue surgically resected from lung metastatic lesions and comparing their gene expression profiles with those from nonpulmonary sites, all coming from breast cancer patients. We show that the gene expression profiles of organ-specific metastatic lesions can be used to predict lung metastasis in breast cancer. We identified a set of 21 lung metastasis–associated genes. Using a cohort of 72 lymph node–negative breast cancer patients, we developed a 6-gene prognostic classifier that discriminated breast primary cancers with a significantly higher risk of lung metastasis. We then validated the predictive ability of the 6-gene signature in 3 independent cohorts of breast cancers consisting of a total of 721 patients. Finally, we show that the signature improves risk stratification independently of known standard clinical variables and a previously established lung metastasis signature based on an experimental breast cancer metastasis model. [Cancer Res 2008;68(15):6092–9]
Neurology of Early Childhood
Authors: Samuel A. Shelburne
Journal: JAMA (1971)

This is the second edition of Dr. Dekaban's book, which first appeared in 1959. The text has a standard format with sections on various neurological diseases, most of which are well described. The author's primary aim is to cover the period from birth to 6 years of age. The influence of mental and motor development on the manifestations of neurological disease in children is emphasized throughout. Many recent advances have not been incorporated in this revised edition. For example, there have been remarkable developments in pediatric neuroradiology, particularly in cerebral and spinal cord angiography. In this book's illustrations, there are 17 x-ray films of the skull and 17 air studies, but no arteriograms and only one myelogram. There is also the glaring omission of the problems of hyperactivity, and of learning disabilities, subjects of increasing importance in pediatric neurology. Some sections on therapy are grossly inadequate, particularly in the field
Abstract 3779: Combination chemoprevention of hepatocellular carcinoma using acyclic retinoid
Authors: Masahito Shimizu, Hisataka Moriwaki
Journal: Cancer Research (2010)

Abstract Background and aims: A malfunction of retinoid X receptor-α (RXRα) due to phosphorylation by the Ras/MAPK signaling pathway is associated with the development of hepatocellular carcinoma (HCC). Acyclic retinoid (ACR: the same material as NIK-333), which has been clinically shown to reduce the incidence of a post-therapeutic recurrence of HCC, can inhibit both the Ras activity and phosphorylation of the ERK and RXRα proteins. The effects of a combination of ACR plus other agents on the inhibition of cell growth in human HCC cells were herein examined to develop a more effective strategy for the prevention of HCC. Methods and results: The combination of ACR plus vitamin K2, which inhibits the phosphorylation of the RXRα protein through the inhibition of Ras/MAPK activation, synergistically induced apoptosis and inhibited the growth of human HCC cells without affecting the growth of normal human hepatocytes. ACR and trastuzumab, the humanized anti-HER2 monoclonal antibody, also synergistically inhibited the activation of HER2, a member of receptor tyrosine kinase (RTK), and its downstream signaling pathways, thus subsequently inhibiting the phosphorylation of RXRα and the growth of HCC cells. ACR in combination with valproic acid, a histone deacetylase inhibitor, also synergistically inhibited the growth of human HCC cells and this was associated with the inhibition of phosphorylation of the RXRα and Akt proteins by valproic acid. Conclusion: The combination of ACR plus a specific agent that targets RTK and its downstream signaling pathways, including the Ras/MAPK and PI3K/Akt pathways, may be able to inhibit the phosphorylation of RXRα and it may therefore be a promising strategy to prevent the development of HCC. ACR, which targets phosphorylated RXRα, may thus play a critical role in preventing the development of HCC when it is used either alone or in combination with other agents. 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 3779.
350. Ectopic Retroviral Expression of LMO2, but Not IL2Rγ, Blocks Human T-Cell Development from CD34+ Progenitor Cells: Implications for Gene Therapy
Authors: Karin Pike-Overzet, Dick de Ridder, Floor Weerkamp, Miranda R.M. Baert, Monique M. Verstegen, Steven J. Howe, Adrian J. Thrasher, Gerard Wagemaker, Jacques J.M. van Dongen, Frank J.T. Staal
Journal: Molecular Therapy (2006)

The occurrence of leukemia in 3 out of 11 patients in a gene therapy trial for SCID-X1 emphasized insertional mutagenesis as an adverse effect. In two out of three patients retroviral integration occurred near the T-cell acute lymphoblastic leukemia (T-ALL) oncogene LIM-only protein 2 (LMO2). It has remained unclear why LMO2 was preferentially targeted. We show here that of classical T-ALL oncogenes, mainly LMO2 is transcribed in CD34+ progenitor cells derived from umbilical cord blood (UCB). Upon stimulation with growth factors typically used in gene therapy protocols, transcription of LMO2, LYL1 and TAL1 increased 2–3 fold in CD34+ UCB cells, whereas the other T-ALL oncogenes remained unaffected. Similarly, when mobilized peripheral blood CD34+ cells were stimulated according to transduction protocols used for clinical SCID-X1 gene therapy trials, the same pattern of T-ALL oncogene transcription was observed, suggesting that cytokine stimulation leads to upregulation of proto-oncogenes irrespective of the source of CD34+ progenitor cells used. Transcription of LMO2, LYL1 and TAL1 is particularly high and their loci could therefore be preferentially accessible for viral integration. Retroviral overexpression of LMO2 in CD34+ cells led to severe abnormalities in human T-cell development, but B-cell, NK cell and myeloid development remained unaffected. The interleukin-2 receptor gamma chain (IL2Rγ), causing SCID-X1 when mutated, has been proposed to act as an oncogene cooperative to LMO2. However, we found that overexpression of IL2Rγ had no effect on T-cell development. Moreover, IL2Rγ normally is expressed at high levels in CD34+ progenitor cells and at even higher levels in the thymus. Thus, transduction of IL2Rγ in CD34+ progenitor cells does not cause ectopic expression of this gene. In conclusion, our data provide an explanation why LMO2 was preferentially targeted over other known T-ALL oncogenes. Furthermore, IL2Rγ does not appear to act as an oncogene. Rather, the normal IL2Rγ chain restores IL7 receptor signalling in the progeny of transduced SCID-X1 cells developing in the thymus, allowing T-cell development to progress to stages where ectopic LMO2 expression hampers T-cell development in the thymus, creating a probable pre-leukemic condition by accumulation of immature cells under intense proliferative pressure.
Single-Pill Combination Regimens for Treatment of HIV-1 Infection
Authors: Monica Gandhi, Rajesh T. Gandhi
Journal: New England Journal of Medicine (2014)

A 52-year-old man with a history of HIV-1 infection and poor medication adherence presents for evaluation. A single-pill regimen is considered. For some patients with HIV-1 infection, combination regimens consisting of one pill to be taken daily can improve adherence.
Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth
Authors: Wiebke Hansen, Marina Hutzler, Simone Abel, Christina Alter, Christian Stockmann, Stefanie Kliche, Juliane Albert, Tim Sparwasser, Shimon Sakaguchi, Astrid M. Westendorf, Dirk Schadendorf, Jan Buer, Iris Helfrich
Journal: The Journal of Experimental Medicine (2012)

Infiltration of Foxp3(+) regulatory T (T reg) cells is considered to be a critical step during tumor development and progression. T reg cells supposedly suppress locally an effective anti-tumor immune response within tumor tissues, although the precise mechanism by which T reg cells infiltrate the tumor is still unclear. We provide evidence that Neuropilin 1 (Nrp-1), highly expressed by Foxp3(+) T reg cells, regulates the immunological anti-tumor control by guiding T reg cells into the tumor in response to tumor-derived vascular endothelial growth factor (VEGF). We demonstrate for the first time that T cell-specific ablation of Nrp-1 expression results in a significant breakdown in tumor immune escape in various transplantation models and in a spontaneous, endogenously driven melanoma model associated with strongly reduced tumor growth and prolonged tumor-free survival. Strikingly, numbers of tumor-infiltrating Foxp3(+) T reg cells were significantly reduced accompanied by enhanced activation of CD8(+) T cells within tumors of T cell-specific Nrp-1-deficient mice. This phenotype can be reversed by adoptive transfer of Nrp-1(+) T reg cells from wild-type mice. Thus, our data strongly suggest that Nrp-1 acts as a key mediator of Foxp3(+) T reg cell infiltration into the tumor site resulting in a dampened anti-tumor immune response and enhanced tumor progression.
Autonomic control of ventricular tachycardia: sympathetic neural influence on spontaneous tachycardia 24 hours after coronary occlusion.
Authors: J B Martins
Journal: Circulation (1985)

This study was performed to determine whether sympathetic nerves influence the rate of ventricular tachycardia occurring spontaneously in dogs 24 hr after occlusion of the anterior descending coronary artery. Seventeen chloralose-anesthetized dogs underwent activation mapping during spontaneous ventricular tachycardia with QRS morphologies similar to those recorded in the conscious state. Bilateral stellate ganglionectomy (n = 8) decreased mean arterial pressure from 71 +/- 4 (mean +/- SE) to 52 +/- 5 mm Hg (p less than .001) and heart rate from 121 +/- 9 to 79 +/- 15 beats/min (p less than .025) by decreasing the number of complexes of ventricular tachycardia from 120 +/- 9 to 49 +/- 15 per minute (p less than .001). Subsequent unilateral sympathetic nerve stimulation (n = 4) was shown to accelerate ventricular tachycardia foci originating from the ipsilateral aspect of the infarction. Regional sympathetic denervation (n = 7) was performed by application of phenol to the epicardium surrounding an electrode at the site of origin of at least one morphology of ventricular tachycardia. Mean arterial pressure did not change, but total heart rate decreased from 122 +/- 9 to 106 +/- 9 beats/min (p less than .01) and the number of complexes of ventricular tachycardia with a morphology arising from the phenol-treated area fell from 68 +/- 12 to 28 +/- 9 (p less than .001). Evidence for regional denervation was documented by prolongation of duration of electrograms and local repolarization times limited to the phenol-treated area. We conclude that sympathetic nerves directly control rate of spontaneous ventricular tachycardia 24 hr after myocardial infarction in the dog.
The World Trade Center Disaster and the Health of Workers: Five-Year Assessment of a Unique Medical Screening Program
Authors: Robin Herbert, Jacqueline Moline, Gwen Skloot, Kristina Metzger, Sherry Baron, Benjamin Luft, Steven Markowitz, Iris Udasin, Denise Harrison, Diane Stein, Andrew Todd, Paul Enright, Jeanne Mager Stellman, Philip J. Landrigan, Stephen M. Levin
Journal: Environmental Health Perspectives (2006)

BackgroundApproximately 40,000 rescue and recovery workers were exposed to caustic dust and toxic pollutants following the 11 September 2001 attacks on the World Trade Center (WTC). These workers included traditional first responders, such as firefighters and police, and a diverse population of construction, utility, and public sector workers.MethodsTo characterize WTC-related health effects, the WTC Worker and Volunteer Medical Screening Program was established. This multicenter clinical program provides free standardized examinations to responders. Examinations include medical, mental health, and exposure assessment questionnaires; physical examinations; spirometry; and chest X rays.ResultsOf 9,442 responders examined between July 2002 and April 2004, 69% reported new or worsened respiratory symptoms while performing WTC work. Symptoms persisted to the time of examination in 59% of these workers. Among those who had been asymptomatic before September 11, 61% developed respiratory symptoms while performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital capacity (FVC) was low in 21%; and obstruction was present in 5%. Among nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S. population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities were significantly associated with early arrival at the site.ConclusionWTC responders had exposure-related increases in respiratory symptoms and pulmonary function test abnormalities that persisted up to 2.5 years after the attacks. Long-term medical monitoring is required to track persistence of these abnormalities and identify late effects, including possible malignancies. Lessons learned should guide future responses to civil disasters.
Protective effects of HOE642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion
Authors: W. Scholz, U. Albus, L. Counillon, H. Gogelein, H.-J Lang, W. Linz, A. Weichert, B. A Scholkens
Journal: Cardiovascular Research (1995)

Objective: The aim was to characterise the new compound HOE642 as a selective and cardioprotective Na+/H+ exchange inhibitor in various models. Methods: The effect of HOE642 was tested in the osmotically activated Na+/H+ exchange of rabbit erythrocytes and in propionate induced swelling of human thrombocytes. Recovery of pH after an NH4Cl prepulse and effects on other ion transport systems by patch clamp technique were investigated in rat cardiomyocytes, NHE subtype specifity of the compound was determined by 22Na+ uptake inhibition in a fibroblast cell line separately expressing subtype isoforms 1–3. Protective effects of HOE642 in cardiac ischaemia and reperfusion by ligation of coronary artery were investigated in isolated working rat hearts and in anaesthetised rats. Results: HOE642 concentration dependently inhibited the amiloride sensitive sodium influx in rabbit erythrocytes, reduced the swelling of human platelets induced by intracellular acidification, and delayed pH recovery in rat cardiomyocytes. In the isolated working rat heart subjected to ischaemia and reperfusion HOE642 dose dependently reduced the the incidence and the duration of reperfusion arrhythmias. It also reduced the the release of lactate dehydrogenase and creatine kinase, and preserved the tissue content of glycogen, ATP, and creatine phosphate. In anaesthetised rats undergoing coronary artery ligation intravenous and oral pretreatment with HOE642 caused a dose dependent reduction or a complete prevention of ventricular premature beats, ventricular tachycardia, and ventricular fibrillation. The compound was well tolerated and neutral to circulatory variables. Other cardiovascular agents tested in this model were not, or were only partly, effective at doses showing marked cardiodepressive effects. Conclusions: HOE642 is a very selective NHE subtype 1 inhibitor showing cardioprotective and antiarrhythmic effects in ischaemic and reperfused hearts. Further development of well tolerated compounds like HOE642 could lead to a new therapeutic approach in clinical indications related to cardiac ischaemia and reperfusion.
The effect of long‐term left ventricular assist device support on myocardial sympathetic activity in patients with non‐ischaemic dilated cardiomyopathy
Authors: Robert S. George, Emma J. Birks, Andrew Cheetham, Carole Webb, Ryszad T. Smolenski, Asghar Khaghani, Magdi H. Yacoub, Andrew Kelion
Journal: European Journal of Heart Failure (2013)
The Hsp90 inhibitor IPI-504 overcomes bortezomib resistance in mantle cell lymphoma in vitro and in vivo by down-regulation of the prosurvival ER chaperone BiP/Grp78
Authors: Gaël Roué, Patricia Pérez-Galán, Ana Mozos, Mónica López-Guerra, Sílvia Xargay-Torrent, Laia Rosich, Ifigènia Saborit-Villarroya, Emmanuel Normant, Elias Campo, Dolors Colomer
Journal: Blood (2010)
Euthyroid Graves's Disease
Authors: Isadore N. Rosenberg
Journal: New England Journal of Medicine (1977)

The infiltrative ophthalmopathy of Graves's disease may precede, accompany or follow the onset of hyperthyroidism. Proptosis, soft-tissue involvement and ophthalmoplegia, occurring in an obviously thyrotoxic patient, or in one with a history of hyperthyroidism, pose no problem, but diagnosis is more difficult when such changes occur in apparently euthyroid persons since not only euthyroid Graves's disease (also termed Graves's ophthalmopathy and endocrine exophthalmos) but primary orbital disorders must then be considered. Werner's observation, 20 years ago,1 that in nine out of 10 cases of euthyroid Graves's disease, uptake of radioiodine by the thyroid gland was not normally suppressed by administered . . .