tbuckley/cabot-search huggingface dataset:
Prognostic Impact of [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography Scanning in the Era of Molecular Oncology
Authors: Jeong-Seon Ryu, In Young Hyun
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: The article entitled, “Prediction of Survival by [F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiotherapy Therapy: Results of the ACRIN 6668/RTOG 0235 Trial,” by Machtay et al that was recently published in Journal of Clinical Oncology was of considerable interest. This study showed that post-treatment peak or maximum standardized uptake value (SUV) had prognostic implication in patients with stage III non–small-cell lung cancer treated with definitive chemoradiotherapy therapy. In previous studies, the role of the positron emission tomography (PET) scan as a predictive or prognostic marker has been investigated by estimation of SUVs, total lesion glycolysis, or metabolic tumor volume in patients with non–small-cell lung cancer. Evidence supporting the relevance of these parameters has accumulated in a variety of clinical settings: surgery, neoadjuvant or adjuvant chemotherapy, concurrent chemoradiotherapy therapy, and palliative chemotherapy. Nevertheless, this study had the merit of being a prospective, well-designed multicenter trial with a large study population. In the era of molecular oncology, we have several suggestions to improve the clinical relevance of the study. First, the primary end point of this study was to find correlation between post-treatment peak SUV and overall survival. However, overall survival is clearly affected by subsequent secondor further-line treatment, especially in patients with EGFR mutations or an anaplastic lymphoma kinase rearrangement. Therefore, in this study, whether or not relevant targeted treatment was administered to patients should have been considered in the analysis of the effect of post-treatment peak SUV as an important confounder. Otherwise, it might be reasonable to use progression-free survival rather than overall survival. Second, with recent advances in high-throughput technologies, such as nextgeneration sequencing, interor intratumoral heterogeneity has been identified and can be associated with survival of patients with cancer. In most investigations, including this study by Machtay et al, assessment of the role of PET scanning has been limited to primary tumor lesions. Thus, in future studies, interor intratumoral heterogeneity among all measurable lesions, preand post-treatment, should be considered to strengthen the predictive or prognostic role of PET scanning. Finally, fluorodeoxyglucose-related glucose metabolism in cancer cells can differ and can be influenced by a variety of genes involved in glucose transporters or intracellular phosphorylation. Therefore, additional investigation is warranted, because changes in expression or mutation of these genes could affect heterogeneity in fluorodeoxyglucose distribution.
Platelet factor 4 release during exercise in patients with coronary artery disease
Authors: Shirley P. Levine, Augustin J. Suarez, Richard R. Sorenson, Nancy M. Raymond, Linda K. Knieriem
Journal: American Journal of Hematology (1984)

Abstract Many recent studies provide evidence that increased platelet activation occurs in a significant number of patients with atherosclerotic coronary artery disease. The mechanisms responsible for this activation are unknown, although there have been studies suggesting a correlation with abnormal lipoproteinemia, acute myocardial infarction, unstable angina, and exercise‐induced myocardial ischemia. We studied 84 patients undergoing standardized treadmill exercise using either a Bruce [N = 63] or symptom‐limited Naughton protocol [N = 21]. In contrast to ten healthy volunteer subjects, the patient group demonstrated a significant increase in plasma concentrations of platelet factor 4 [PF4] between pre‐ and postexercise blood samples confirming earlier reports of exercise‐induced platelet activation and secretion. As with previous studies, however, only a subset of patients demonstrated this response. When the entire group was analyzed for the presence or absence of electrocardiographic ischemic changes and the presence of documented versus suspected coronary artery occlusions, there were no differences noted between groups that explained the variable responses measured. However, there was a significant difference between patient groups when analyzed by whether or not they were being treated with β‐blocking agents. Patients who were being treated with propranolol or one of the longer‐acting β‐blocking agents did not have a significant increase in plasma PF4 following exercise, in contrast to patients who were not β‐blocked. Plasma concentrations of epinephrine, norepinephrine, and lactic acid were measured in 49 patients and all normal subjects. There was no correlation between the changes in plasma PF4 concentrations and any of these three variables, suggesting that platelet activation was not occurring through direct platelet activation by circulating catecholamines. This study provides further evidence that there is a subset of CAD patients with platelet hyperactivity. This is the first time that β‐blockade has been demonstrated to modify this platelet response. The effectiveness of β‐blocking agents in CAD may be in part related to their antiplatelet effect.
Control of cellular influx in lung and its role in pulmonary toxicology.
Authors: W S Lynn
Journal: Environmental Health Perspectives (1984)

The pulmonary influx of cytotoxic inflammatory cells, normally, in response to external toxins, is now thought to be etiologic in many of the disease syndromes of man, such as bronchitis and emphysema. Many types of effector inflammatory cells are involved, e.g., eosinophils, neutrophils, T-lymphocytes, monocytes. The diseases are characterized either by tissue destruction or by tissue hyperplasia. Agents which initiate the influx and cytotoxic secretions by these cells are legion and in general are not cell-specific. They include agents, such as phorbol esters, formyl peptides-complement fragments, elastin fragments, fatty acids (leukotrienes) as well as many uncharacterized excretions of inflammatory cells themselves, which react with specific receptors on the inflammatory cells, and secreted proteins such as fibronectin. Other agents, such as linoleic acid, digitonin and hydroxy fatty acids which are not bound by specific receptors also activate motility of inflammatory cells. The precise role of the above multiple cytotoxins in specific cellular fluxes in most pulmonary disease remains undefined. Similarly, the mechanism of cytotoxicity used by specific invading cells in specific pulmonary syndromes remains unclear. In general, macrophages are thought to destroy using specific proteases, neutrophils use oxidant radicals and proteases and eosinophils use basic surface active peptides. T-cells kill by unknown mechanisms. However, in specific clinical syndromes, it is usually not clear which cell is the cytotoxic culprit, nor is the mechanism of destruction usually known.
TCT-495 VerifyNow in DIabetes high-on-treatment platelet reactivity: a pharmacodynamic study on switching from clopidogrel to prasugrel (VERDI study)
Authors: José María Cubero Gómez, Juan Acosta Martinez, Cristina Mendias Benitez, Luis Díaz de la Llera, Monica Fernandez-Quero, Agustin Guisado Rasco, Manuel Villa Gil-Ortega, Angel Sanchez Gonzalez
Journal: Journal of the American College of Cardiology (2014)
A piece of my mind. When to touch
Authors: D. Morse
Journal: JAMA (1990)

I had been called about the patient before. She was a young woman, in her 20s, with AIDS. She'd been hospitalized most recently because of intractable seizures, probably secondary to toxoplasmosis and lymphoma. The last time I was on call, her seizures were being treated with diazepam, and I was asked to cross-cover at night for her regular resident physician because she was still seizing. I went to her room and encountered her mother, who was clearly distraught. She begged me to tell her whether the end was near, whether she should stay the night. I didn't know what to say; although I sensed her daughter's death wasn't imminent, I couldn't promise. I told her this. She seemed incredibly despondent, but I had other calls to answer and asked the nurse to try to console her. A few days later, I was again called about the patient. She was a
Intraarterial Treatment of GEP NET: 68Ga-DOTATOC SUV Cannot Predict 90Y-DOTATOC Uptake
Authors: Claudia Brogsitter, Diana Faulhaber, Jörg Kotzerke
Journal: Clinical Cancer Research (2011)

Kratochwil and colleagues (1) demonstrate in their very elegant study that selective intraarterial (i.a.) application of 68Ga-DOTATOC into the feeding artery of liver metastases from neuroendocrine tumors leads to a significantly higher SUV compared with intravenous (i.v.) application. An advantage of their study is the absence of therapeutic interventions as a confounding factor. This is a limitation in other studies comparing different therapeutic approaches as it commonly restricts recruitment of suitably large, homogeneous patient groups.However, we do not believe that these data can be extrapolated to suggest a higher tumor uptake or a greater therapeutic efficacy of 90Y- or 177Lu-DOTATOC following i.a. application.Following our previously reported experience with i.a. application of 131I-MIBG (2), we have so far treated 5 patients with 90Y-DOTATOC intravenously, followed by i.a. treatment 6 months later. We could not observe a consistently higher tumor uptake following i.a. application. Intraarterial-to-intravenous uptake ratios varied widely in our patients, from 0.45 to 2.74.We are aware that ours is a very small group of patients, but due to the markedly different receptor affinities of 68Ga-DOTATOC and 90Y-DOTATOC we do not expect a significantly greater tumor uptake following i.a. application of 90Y-DOTATOC.Heppeler and colleagues (3) showed that SSR2 receptor affinity of 67Ga-DOTATOC was 4 to 5 times higher than that of 90Y- and 111In-DOTATOC, respectively. In their study, 67Ga-DOTATOC showed a significantly higher tumor and lower renal uptake than the other 2 compounds. These data lead us to conclude that, in contrast to 68Ga-DOTATOC, a significantly higher tumor uptake after i.a. application cannot be expected for 90Y-DOTATOC.No potential conflicts of interest were disclosed.
The pulmonary physician in critical care * 4: Nosocomial pneumonia
Authors: S Ewig
Journal: Thorax (2002)

Much progress has been made in the understanding of nosocomial pneumonia but important issues in diagnosis and treatment remain unresolved. The controversy over diagnostic tools should be closed. Instead, every effort should be made to increase our ability to make valid clinical predictions about the presence of ventilator associated pneumonia and to establish criteria to guide restricting empirical antimicrobial treatment without causing patient harm. More emphasis must be put on local infection control measures such as routine surveillance of pathogens, definition of controlled policies of antimicrobial treatment, and effective implementation of strategies of prevention.
STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients
Authors: David Vasquez-Dunddel, Fan Pan, Qi Zeng, Mikhail Gorbounov, Emilia Albesiano, Juan Fu, Richard L. Blosser, Ada J. Tam, Tullia Bruno, Hao Zhang, Drew Pardoll, Young Kim
Journal: Journal of Clinical Investigation (2013)

Myeloid-derived suppressor cells (MDSC) play a key immunosuppressive role in various types of cancer, including head and neck squamous cell carcinoma (HNSCC). In this study, we characterized CD14+HLA-DR–/lo cells sorted from the tumors, draining lymph nodes, and peripheral blood of HNSCC patients. CD14+HLA-DR–/lo cells were phenotyped as CD11b+, CD33+, CD34+, arginase-I+, and ROS+. In all 3 compartments, they suppressed autologous, antigen-independent T cell proliferation in a differential manner. The abundance of MDSC correlated with stage, but did not correlate with previous treatment with radiation or subsites of HNSCC. Interestingly, MDSC from all 3 compartments showed high phosphorylated STAT3 levels that correlated with arginase-I expression levels and activity. Stattic, a STAT3-specific inhibitor, and STAT3-targeted siRNA abrogated MDSC’s suppressive function. Inhibition of STAT3 signaling also resulted in decreased arginase-I activity. Analysis of the human arginase-I promoter region showed multiple STAT3-binding elements, and ChIP demonstrated that phosphorylated STAT3 binds to multiple sites in the arginase-I promoter. Finally, rescue of arginase-I activity after STAT3 blockade restored MDSC’s suppressive function. Taken together, these results demonstrate that the suppressive function of arginase-I in both infiltrating and circulating MDSC is a downstream target of activated STAT3.
Tackling Tuberculosis in Latvia
Authors: Melanie Zipperer
Journal: PLoS Medicine (2005)

0380 With a forceful gesture, the delicate blond unlocks the heavy door of a cell in Riga’s Central Prison clinic (Figure 1). Her name is Dr. Inga Nagele. She is the head of the clinic’s tuberculosis (TB) unit. She opens the door to check on three female prisoners who have just been admitted. The conditions in the cell are bleak. Washing hangs on a line that stretches from one wall to the other. The bars on the small window hardly let any light into the room, and a bucket in the corner serves as a toilet. All the women were infected with TB at the prison. “Living conditions in Latvia’s prisons are miserable. This is ideal for a relentless spread of the life-threatening lung bacteria and other communicable diseases”, says Dr. Nagele. Because of permanent overcrowding, poor hygiene, and frequent relocation of prisoners within Latvia’s 15 prisons, two-thirds of inmates infected with TB developed the disease once they were locked up, she says. Latvia has 352 prisoners per 100 000 individuals in the population [1]. This number makes it one of the countries with the highest proportion of prisoners in the European Union, according to Mihails Azarenko, Chief of Riga’s Central Prison. It is particularly high when compared with Denmark, for example, which has only 64 prisoners per 100 000 individuals [1].
Current Concepts in Brain Resuscitation
Authors: Mark C. Rogers
Journal: JAMA (1989)

The area of cerebral resuscitation has become an exciting area of research in critical care medicine. It is a complicated field, however, which has seen attempts to protect the brain using a single therapy such as barbiturates ultimately disappoint investigators in the field. It is likely that much more work needs to be done in understanding the intracellular metabolic and biochemical effects of ischemia before therapies can be designed that are likely to be effective. This work might ultimately require knowledge of how ischemia or hypoxia interrupt cellular RNA and DNA machinery before these effective therapies can be developed. Before we are discouraged by the difficulty of the task, however, it is useful to review how much progress has been made in understanding the pathophysiology of ischemic brain injury in the past decade, so that we may be challenged to continue our efforts in this exciting area of critical care medicine.
South Asian health: what is to be done?
Authors: Evangelia Chryssafidou, Theodoros N Arvanitis, Khalid S Khan, Aravinthan Coomarasamy
Journal: BMJ (2004)

South Asian health: what is to be done? Amalgamation of South Asia's medical community will benefit allEditor-The BMJ deserves credit for providing the spark necessary to activate the medical community of the South Asian countries, with their limited resources, unstable governments, and uncommitted politicians pitching in with solutions for public health problems.Amalgamation of South Asia's medical community will ensure benefits to all its constituents.Strength will flow from unity of purpose focused on achievable targets with a structured and pragmatic plan of realistic objectives.The impossible can be made possible.There is a wealth of talent and experience in the South Asian countries in traditional and complementary systems of medicine, which have great potential for providing relief to millions of people at minimal or no cost to the exchequer.Ayurveda, the unani system, homoeopathy, herbal medicine, yoga, and meditation are powerful modalities for providing some remedies to the poor and ailing population of South Asia.Education is the bedrock on which all health practices are based.Knowledge of cleanliness, sanitation, clean potable water, and basic amenities for primary health in every village is an admirable beginning.The public and private sectors have distinctive roles.There must be harmony, cooperation, discipline, and monitoring to ensure optimal use of resources.This needs to be orchestrated by the government agencies designated to run a country's health programmes.
Pregnancy-Related Thromboembolism
Authors: Richard V. Lee
Journal: Annals of Internal Medicine (1997)

Letters15 July 1997Pregnancy-Related ThromboembolismRichard V. Lee, MDRichard V. Lee, MDState University of New York at Buffalo; Buffalo, NY 14222Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-2-199707150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:I thank Drs. Vandenbroucke and Rosendaal for reinforcing the importance of old-fashioned history taking as a screening strategy for thrombophilic predisposition. In a litigious venue, unfortunately, the availability of a quantifiable test often means that the new technique supplants the old and becomes the standard. And after the presence of thrombophilia has been identified, doing nothing during pregnancy (a condition highly publicized as a hypercoagulable state) is risky even when doing something like anticoagulation has clearly defined risks. In light of new studies of genetic thrombophilic conditions, neither the older literature about pregnancy and thromboembolism nor the literature ... Author, Article, and Disclosure InformationAuthors: Richard V. Lee, MDAffiliations: State University of New York at Buffalo; Buffalo, NY 14222 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1997Volume 127, Issue 2 Page: 165 Keywords Genetic diseases Heparin Pregnancy Prophylaxis Prospective studies Thromboembolism ePublished: 15 August 2000 Issue Published: 15 July 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Philip John Simpson
Authors: A. Harnden
Journal: BMJ (2002)

General practitioner Jarrow 1992-5 and Sunderland (b 1960; q Newcastle 1983; MRCGP, DA, DRCOG), died from colon cancer on 27 December 2001.

After anaesthetic work, GP vocational training, and posts in New Zealand and Australia, he returned to his roots in the north east and was appointed a GP principal in Jarrow. His local accent and straightforward style enabled him to communicate effectively with his practice population. In 1995 he was forced to take early retirement when he developed chronic autoimmune hepatitis. Two years later the aetiology was determined to be secondary to minocycline and he returned to part time work. He learnt to fly at the old Sunderland airport and, while in New Zealand, he piloted a memorable flight over Mount Cook. He leaves a wife, Fiona; and three young sons.
Towards the Prevention of Eating Disorders
Authors: G.F. Huon, M. Wootton
Journal: Psychotherapy and Psychosomatics (1987)

The high incidence of disordered eating among female adolescents and young adult women has been noted in surveys carried out in Australia, the USA, New Zealand and the UK. While a critical feature that distinguishes those who go on to develop anorexia nervosa or bulimia nervosa is their sense of a loss of control over their eating, the psychological and nutritional concomitants of this loss of control have not been empirically investigated. Preliminary findings are described from an experimental study which is aimed at systematically investigating the relationship between dietary composition and consumatory patterns, hunger and satiety. The results are discussed in terms of the possible role of 'diet' in perpetuating the symptoms of bulimia nervosa and anorexia nervosa.
On the mechanism of impaired insulin secretion in chronic renal failure.
Authors: G Z Fadda, S M Hajjar, A F Perna, X J Zhou, L G Lipson, S G Massry
Journal: Journal of Clinical Investigation (1991)

It has been suggested that a sustained rise in resting levels of cytosolic calcium [Ca2+]i of pancreatic islets is responsible for impaired insulin secretion in chronic renal failure (CRF). Evidence for such an event is lacking and the mechanisms through which it may affect insulin secretion are not known. Studies were conducted in normal, CRF, and normocalcemic, parathyroidectomized (PTX) CRF rats to answer these questions. Resting levels of [Ca2+]i of islets from CRF rats were higher (P less than 0.01) than in control of CRF-PTX rats. [3H]2-deoxyglucose uptake and cAMP production by islets were not different in the three groups. Insulin content of, and glucose-induced insulin secretion by islets from CRF rats was lower (P less than 0.01) than in control and CRF-PTX rats. In contrast, glyceraldehyde-induced insulin release by CRF islets was normal. Basal ATP content, both glucose-stimulated ATP content and ATP/ADP ratio, net lactic acid output, Vmax of phosphofructokinase-1, and Ca2+ ATPase of islets from CRF rats were lower (P less than 0.02-less than 0.01) than in normal or CRF-PTX animals. Data show that: (a) Glucose but not glyceraldehyde-induced insulin secretion is impaired in CRF; (b) the impairment in glucose-induced insulin release in CRF is due to a defect in the metabolism of glucose; (c) this latter defect is due to reduced ATP content induced partly by high [Ca2+]i of islets; and (d) the high [Ca2+]i in islets of CRF rats is due to augmented PTH-induced calcium entry into cells and decreased calcium extrusion from the islets secondary to reduced activity of the Ca2+ ATPase.
Mobility aids and appliances for disabled children.
Authors: K. S. Holt
Journal: BMJ (1991)

compression respond poorly to treatment and are associated with a high morbidity, confining patients to hospital for most, if not all, of their remaining lives.If those patients most likely to develop a major neuro- logical complication can be identified it seems important to prevent it.Thus to irradiate painful areas of increased 9Tc uptake in the spine as determined by radioisotope bone scanning will do little harm and may prevent paraplegia in many patients.
Prevalence of macular pattern dystrophy in maternally inherited diabetes and deafness
Authors: Pascale Massin, Marie Virally-Monod, Bernard Vialettes, Michel Paques, Henri Gin, Béatrice Porokhov, Sophie Caillat-Zucman, Philippe Froguel, Véronique Paquis-Fluckinger, Alain Gaudric, Pierre-Jean Guillausseau
Journal: Ophthalmology (1999)
Gut-friendly B cells?
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

![Graphic][1] 

IgM+ B cells (brown) develop in the mouse gut even when the spleen and gut lymphoid tissues are missing. On page 

[1343][2], Shimomura et al. identify a group of B cells that rebels against convention: unlike other B cells, this group matures in the gut and might
Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis
Authors: Andres Jerez, Yuka Sugimoto, Hideki Makishima, Amit Verma, Anna M. Jankowska, Bartlomiej Przychodzen, Valeria Visconte, Ramon V. Tiu, Christine L. O'Keefe, Azim M. Mohamedali, Austin G. Kulasekararaj, Andrea Pellagatti, Kathy McGraw, Hideki Muramatsu, Alison R. Moliterno, Mikkael A. Sekeres, Michael A. McDevitt, Seiji Kojima, Alan List, Jacqueline Boultwood, Ghulam J. Mufti, Jaroslaw P. Maciejewski
Journal: Blood (2012)