tbuckley/cabot-search huggingface dataset:
Non–Insulin-Dependent Diabetes Mellitus and Fasting Glucose and Insulin Concentrations Are Associated With Arterial Stiffness Indexes
Authors: Veikko Salomaa, Ward Riley, Jeremy D. Kark, Christopher Nardo, Aaron R. Folsom
Journal: Circulation (1995)

Background Cardiovascular diseases are the most common cause of disability and death among subjects with non–insulin-dependent diabetes mellitus (NIDDM). The atherosclerotic process begins during the prediabetic phase characterized by impaired glucose tolerance, hyperinsulinemia, and insulin resistance. In vitro studies have suggested that glucose and insulin can substantially alter the structure and function of the arterial wall and affect the development of atherosclerosis. Methods and Results We performed a cross-sectional study of the relation of arterial stiffness indexes with glucose tolerance and serum insulin concentrations. Several indexes of common carotid artery stiffness were assessed with noninvasive ultrasound methods in a biracial sample of 4701 men and women 45 to 64 years of age in the Atherosclerosis Risk in Communities (ARIC) Study. Arterial compliance (AC), stiffness index (SI), pressure-strain elastic modulus (Ep), and Young’s elastic modulus (YEM) were calculated. YEM includes wall (intima-media) thickness and thus gives an estimate of arterial stiffness controlling for wall thickness. All indexes of arterial stiffness were higher with increasing concentrations of fasting glucose. This finding was consistent in both black and white examinees and in both sexes. A 25% increase in fasting glucose (approximately 1 SD) was associated in nondiabetic white men with a 5.8% (95% CI, −9.6% to −1.9%; P =.004) decrease in AC and increases of 5.8% (95% CI, 2.0% to 9.7%; P =.002) in SI, 11.3% (95% CI, 6.9% to 15.9%; P &lt;.001) in Ep, and 11.2% (95% CI, 6.2% to 16.6%; P &lt;.001) in YEM. In nondiabetic white women, the corresponding predicted changes were a decrease of 15.0% (95% CI, −18.2% to −11.7%; P &lt;.001) in AC and increases of 16.6% (95% CI, 12.5% to 20.8%; P &lt;.001) in SI, 23.2% (95% CI, 18.4% to 28.2%; P &lt;.001) in Ep, and 19.2% (95% CI, 14.0% to 24.7%; P &lt;.001) in YEM. Glucose and insulin contributed synergistically to the increase in stiffness indexes. Insulin and triglycerides also had a synergistic association with stiffness indexes. Conclusions Our findings are compatible with the view that persons with NIDDM or borderline glucose intolerance have stiffer arteries than their counterparts with normal glucose tolerance and that the decreased elasticity is independent of artery wall thickness. The joint effect of elevated glucose, insulin, and triglycerides can have a considerable impact on arterial stiffness and play an important role in the early pathophysiology of macrovascular disease in NIDDM.
Visions for Change in U.S. Health Care — The Players and the Possibilities
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2009)

Under the incoming presidential administration, U.S. Democratic leaders are determined to achieve a long-elusive goal: securing “affordable, accessible health care for every single American,” as President-elect Barack Obama put it recently. Recognizing the blunders that doomed the reform effort of President Bill Clinton 16 years ago, the new administration is working closely with Congress to craft a bill that will attract sufficient support to ensure enactment.Although some critics argue that we can ill afford the costs of expanded coverage and other reforms with the economy in recession and an ever-growing federal deficit, Obama counters that these are pocketbook issues, . . .
Immunology of Clinical and Experimental Diabetes
Authors: David L. Horwitz
Journal: JAMA (1985)

The paths of immunology and diabetes cross at several levels. First, increasing evidence suggests the importance of immunologic factors in the etiology (and perhaps pathogenesis) of diabetes. Second, certain complications of diabetes, such as insulin allergy and some types of insulin resistance, are immune mediated. Finally, major immunologic problems must be overcome before diabetes can be cured by pancreatic or islet transplantation. The chapters of this book provide comprehensive reviews of all of these areas.  The book is divided into two sections, experimental and clinical; the distinction is evidently based on whether the emphasis is mainly on animal or human studies. However, even the clinical section is primarily devoted to basic investigation, and the volume should not be considered as a reference work for patient care. In fact, the one chapter that is primarily oriented to therapy, that on insulin hypersensitivity, contains no more detail than most clinical textbooks. Furthermore,
TNFR1 Signaling and IFN-γ Signaling Determine whether T Cells Induce Tumor Dormancy or Promote Multistage Carcinogenesis
Authors: Nele Müller-Hermelink, Heidi Braumüller, Bernd Pichler, Thomas Wieder, Reinhard Mailhammer, Katrin Schaak, Kamran Ghoreschi, Amir Yazdi, Roland Haubner, Christian A. Sander, Ralph Mocikat, Markus Schwaiger, Irmgard Förster, Ralph Huss, Wolfgang A. Weber, Manfred Kneilling, Martin Röcken
Journal: Cancer Cell (2008)
P16.28 * INTRAOPERATIVE CEREBRAL GLIOMA CHARACTERIZATION WITH CONTRAST ENHANCED ULTRASOUND (CEUS)
Authors: F. Prada, L. Mattei, M. Del Bene, C. Casali, A. Filippini, F. Legnani, A. Perin, A. Saladino, I. Vetrano, F. DiMeco
Journal: Neuro-Oncology (2014)

BACKGROUND: Contrast Enhanced Ultrasound (CEUS) is a dynamic and continuous modality that offers a real-time direct view of vascularization and flow distribution patterns of different organs and type of tumors. Nevertheless its intraoperative use for brain tumors visualization has been performed few times, and there are no guidelines on this regard. Furthermore a thorugh characterization of cerebral glioma had never been performed. OBJECTIVE: To describe the different patterns of enhancement of cerebral gliomas using the CEUS technique. METHODS: We performed intra-operative CEUS in an off-label setting in 69 patients undergoing surgery for cerebral glioma. An on-site and a post-procedural semi-quantitative analysis was performed for each case, evaluating CEUS parameters: timing, degree of CE and contrast distribution. RESULTS: Both low grade glioma (LGG) and high grade glioma (HGG) appear hyper-echoic relative to the adjacent brain parenchyma on B-mode US. Different contrast enhancement patterns were observed according to lesion characteristics: LGG showed a dotted or diffuse appearance with a slower and delayed arterial and venous phase compared with HGG, whereas HGG have a more nodular, non-homogeneous appearance, with faster and major contrast enhancement. CONCLUSION: Our study characterizes for the first time, human brain glioma with CEUS, giving us further insight regarding the biology of these tumors: being a dynamic and continuous modality it offers a real-time direct view of the tumor perfusion and of the afferent and efferent vessels. CEUS is a fast, safe, dynamic, real-time, economic tool that might be helpful during surgery in differentiating malignant and benign gliomas and refining the surgical strategy.
Sulfhemoglobinemia
Authors: Constance M. Park, Ronald L. Nagel
Journal: New England Journal of Medicine (1984)

SULFHEMOGLOBIN, methemoglobin, and the M hemoglobins must be considered when one is evaluating the cyanotic patient. Sulfhemoglobin is a green-pigmented molecule with a sulfur atom incorporated into the porphyrin ring and a markedly reduced oxygen affinity that makes it ineffective for oxygen transport. It has been associated with drug abuse,1 2 3 4 5 6 7 occupational exposure to sulfur compounds,8 , 9 and recently, environmental exposure to polluted air.10 In sulfhemoglobinemia, methemoglobinemia, and the presence of M hemoglobins in the blood, cyanosis is not itself a sign of respiratory insufficiency. Rather, the slate-gray skin color is the result of the spectral characteristics of the abnormal pigments. The . . .
Left Ventricular Dynamics in Complete Right Bundle-Branch Block with Left Axis Deviation of QRS
Authors: J. BARAGAN, F. FERNANDEZ, B. COBLENCE, Y. SAAD, J. LENÈGRE
Journal: Circulation (1970)

The time intervals defined by the simultaneous recording of an electrocardiogram, phonocardiogram, indirect carotid pulse curve, and apexcardiogram made it possible to compare the left ventricular (LV) dynamics in a group of 33 cases of complete right bundle-branch block with left axis deviation (RBBB-LAD) with two control groups, one consisting of 30 cases of complete right bundle-branch block without left axis deviation (RBBB without LAD) and the other of 30 cases of left axis deviation (LAD) alone. The LV dynamics of RBBB-LAD differed from those of both control groups of RBBB without LAD and of LAD alone by a significantly late onset of LV ejection in the former, resulting from both late onset and slow rise of LV contraction. On the other hand, the delayed LV activity was not significantly different between the group of RBBB-LAD and a previously studied group of complete left bundle-branch block. Normal limits for these intervals were looked for to make it possible to diagnose a late LV activity in the individual patient, and so provide a further argument in the discussion for an eventual cardiac pacing in doubtful cases. Finally, it was not felt possible to use these intervals to try to localize the site of the conduction disturbance, whether in the bundle branch or in the ventricular wall itself.
Improvement of left ventricular wall synchronization with multisite ventricular pacing in heart failure: a prospective study using Doppler tissue imaging
Authors: Stephane Lafitte, Stephane Garrigue, Jean‐Marie Perron, Pierre Bordachar, Sylvain Reuter, Pierre Jaïs, Michel Haïssaguerre, Jacques Clementy, Raymond Roudaut
Journal: European Journal of Heart Failure (2003)
A conduit to imbecility
Authors: Peter Davies
Journal: BMJ (2005)

T hey say that the road to hell is paved with good intentions. And intentions do not come any better than those of the healing professions. We want to help others and so to empower people to be themselves. We are powerfully trained, conscientious, and somewhat driven.

And yet despite the empowering efforts of the healing professions the public seems to be developing an ever greater taste and apparent need for the services of our professions. The patient or client base is growing, and all the while the professionals say they are empowering the patients. If patients are really being empowered, how come there are more of them and they are staying around longer?

There is a deep paradox between the expressed aim of professional services to empower patients and the ever greater demand for professional services from the thus empowered patients. I want to explore this paradox in this essay.

> “Normal? We just haven't examined him closely enough yet!”

In the classic medical model of disease, patients …
Ewing??s Sarcoma Seen as a ???Cold??? Lesion on Bone Scans
Authors: DAVID BUSHNELL, PARVEZ SHIRAZI, NANDA KHEDKAR, JOHN BLANK
Journal: Clinical Nuclear Medicine (1983)

A case is reported of a documented Ewing's sarcoma that appeared as an area without tracer accumulation on a Tc-99m HDP bone scan. We, therefore, emphasize the need to consider such a tumor as a possible cause for a “cold” lesion on bone scan.
Tomographic Fluorescence Mapping of Tumor Targets
Authors: Xavier Montet, Vasilis Ntziachristos, Jan Grimm, Ralph Weissleder
Journal: Cancer Research (2005)

Abstract Methods that allow robust imaging of specific molecular targets and biological processes in vivo should have widespread applications in biology and clinical medicine. Here we use a quantitative, three-dimensional fluorescence-mediated tomographic technique (FMT) that enables rapid measurements of fluorochrome-based affinity tags in live xenograft models. We validate the method by showing its sensitivity in quantitating tumor angiogenesis and therapeutic modulation using an anti–vascular endothelial growth factor antibody. Furthermore, we show the feasibility of simultaneous multichannel measurements of distinct biological phenomena such as receptor tyrosine kinase expression and angiogenesis. FMT measurements can be done serially, with short imaging times and within the same live animal. The described method should be valuable for rapidly profiling biological phenomena in vivo.
Cholera on a Gulf Coast Oil Rig
Authors: Jeffrey M. Johnston, Deborah L. Martin, James Perdue, Louise M. McFarland, Charles T. Caraway, Edwin C. Lippy, Paul A. Blake
Journal: New England Journal of Medicine (1983)

A single case of severe diarrhea on a floating Texas oil rig was followed two days later by what proved to be the largest outbreak of cholera in the United States in over a century. After isolation of toxigenic Vibrio cholerae El Tor Inaba of the typical United States phage type from the index patient's stool, the ensuing investigation detected 14 additional cases of cholera and one asymptomatic infection serologically. Infection was associated with eating rice on the oil rig on a particular day (P = 0.03) when an open valve permitted the rig's drinking-water system to be contaminated by canal water containing sewage (including that from the index patient) discharged from the rig. The rice had been rinsed in the contaminated water after cooking, and before being served it had been maintained at a temperature that allows V. cholerae 01 to multiply. Toxigenic V. cholerae 01 is persisting in the United States, and large common-source outbreaks of cholera can occur if proper sanitation is not maintained.
Abstract 4507: Utilizing the targeting properties of elastin-like polypeptide to safely deliver a potent doxorubicin derivative.
Authors: Leslie R. Walker, Eddie Perkins, Khalid Abu Ajaj, Felix Kratz, Drazen Raucher
Journal: Cancer Research (2013)

Abstract N-butyldiacetate doxorubicin (NBD) is a derivative of a common chemotherapeutic agent that is three to four orders of magnitude more potent that the its parent compound. Targeting such a potent drug to the tumor, relies on an effective tumor targeting strategy. For this purpose, we have developed a hypothermic approach and developed a new macromolecular conjugate by coupling NBD to elastin-like polypeptide (ELP), a macromolecule that is soluble at normal physiological temperature but aggregates in the presence of heat (40-42 °C). Attaching NBD to ELP holds the promise of accumulating NBD effectively in the tumor while sparing healthy tissue. ELP is a macromolecule that is soluble at normal physiological temperature but aggregates in the presence of heat (40-42 °C). The ELP delivery system, SynB1-ELP-NBD, consists of 3 parts: a) a cell-penetrating peptide to facilitate entry through the cell membrane, b) ELP to allow thermal targeting, and c) an acid-sensitive derivative of doxorubicin, NBD. Preliminary results in the S2013 pancreatic cancer cell line have been promising. The IC50 of free doxorubicin is ∼9 μM, while the IC50 of SynB1-ELP-NBD is 1 nM. Very little is known about the mechanism of NBD inside the cell. Using flow cytometry, we compared apoptosis, cell cycle arrest, and generation of reactive oxygen species of SynB1-ELP, SynB1-ELP-NBD, and free NBD. While SynB1-ELP had very little effect on the cell cycle, generation of ROS, and less than 10% apoptotic cells, SynB1-ELP-NBD and free NBD were more active during the S phase at the expense of G1, generated 6× more ROS compared to control cells, and 80% of cells were apoptotic or necrotic after 72 h treatment. In vitro, SynB1-ELP-NBD works very similarly to free NBD, but safe delivery is the goal. In a maximum tolerated dose study, the animals were able to tolerate 2.5 times more NBD when it was attached to ELP compared to free NBD. This delivery system makes it possible to deliver larger amounts of a highly potent doxorubicin derivative to tumor-bearing animals and a comparative in vivo study in a pancreatic cancer mouse model is ongoing. Citation Format: Leslie R. Walker, Eddie Perkins, Khalid Abu Ajaj, Felix Kratz, Drazen Raucher. Utilizing the targeting properties of elastin-like polypeptide to safely deliver a potent doxorubicin derivative. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4507. doi:10.1158/1538-7445.AM2013-4507
Satb2 Is a Postmitotic Determinant for Upper-Layer Neuron Specification in the Neocortex
Authors: Olga Britanova, Camino de Juan Romero, Amanda Cheung, Kenneth Y. Kwan, Manuela Schwark, Andrea Gyorgy, Tanja Vogel, Sergey Akopov, Mišo Mitkovski, Denes Agoston, Nenad Šestan, Zoltán Molnár, Victor Tarabykin
Journal: Neuron (2008)
Shortage of preregistration posts
Authors: B. D. Apthorp
Journal: BMJ (1969)

to close, the general practitioner is barred from participation in hospital medicine, and the frustration of our future registrar-trained general practitioner is going to be unimagin- able.With a six-year compulsory post- graduation training, it will be interesting to see what our future general practitioner will demand as an equitable level of remuneration.Of course, adequate postregistration ex- perience should be encouraged, but by volun- tary, not by compulsory, methods, and the system of clinical assistantships greatly ex- tended to permit the participation of those general practitioners with the training and the desire to combine general practice with continuing hospital work.As usual nothing is said about putting general medical services on the realistic basis of part payment by the
TWO DEATHS FROM THE ADMINISTRATION OF BARIUM SALTS
Authors: WILLIAM D. McNALLY
Journal: JAMA (1925)

Poisoning by barium salts is comparatively rare, in view of the large number of barium meals given for fluoroscopic or roentgen-ray studies, and the frequent occurrence in the arts. Barium chlorid is used in the staining of wool, the nitrate and the chlorate in the green fires of the pyrotechnist, the carbonate and oxid in the manufacture of glass, and the carbonate as a rat poison. The sulphate is used as an adulterant of white powder and in white paints. The sulphid under various names is used as a depilatory. Most of the barium intoxications noted in the literature were due to mistakes or impurities in medicinal formulas, or carelessness in the labeling of the chemicals and compounding. Barium is found in the Harrogate to the extent of about three to six parts per hundred thousand. The poisonous character of the soluble barium salts was early recognized by James Watt,
Hamstring <i>v</i> patellar tendon autografts: Author's reply
Authors: David J Biau
Journal: BMJ (2006)

EDITOR—We hope that doctors will give more information about the outcome and problems related to both reconstructions and that young orthopaedic surgeons will take more interest in hamstring autografts.

Meta-analyses are not free of bias. The quality of reporting in surgical trials needs to be improved, and multicentre randomised controlled trials are needed to overcome sample size issues. We are currently performing …
Revalidation for general practitioners: randomised comparison of two revalidation models
Authors: David Bruce, Katie Phillips, Ross Reid, David Snadden, Ronald Harden
Journal: BMJ (2004)

To compare two models of revalidation for general practitioners.Randomised comparison of two revalidation models.Primary care in Tayside, Scotland.66 Tayside general practitioners (principals and non-principals), 53 of whom completed the revalidation folders. Interventions Two revalidation models: a minimum criterion based model with revalidation as the primary purpose, and an educational outcome model with emphasis on combining revalidation with continuing professional development.Feasibility and acceptability of each approach and effect on the doctor's continuing professional development. The ability to make a summative judgment on completed models and whether either model would allow patient groups to have confidence in the revalidation process.The criterion model was preferred by general practitioners. For both models doctors reported making changes to their practice and felt a positive effect on their continuing professional development. Summative assessment of the folders showed reasonable inter-rater reliability.The criterion model provides a practical and acceptable model for general practitioners to use when preparing for revalidation.
Imprints of disease at GNAS1
Authors: Marc Lalande
Journal: Journal of Clinical Investigation (2001)

GNAS1 encodes the α subunit of the Gs protein (Gsα), which couples hormonal stimulation of multiple cell surface receptors to the activation of adenylate cyclase. GNAS1 maps to the chromosome 20q13 region and is associated with several human endocrine disorders, including Albright hereditary osteodystrophy (AHO) (also termed pseudopseudohypoparathyroidism). AHO is characterized by short stature, subcutaneous calcification, and brachydactyly and is caused by mutations that inactivate Gsα (1–3). GNAS1 mutations also cause pseudohypoparathyroidism type IA (PHPIA), a disease that displays the features of AHO but, in addition, is characterized by resistance to the peripheral action of multiple hormones, including parathyroid hormone.
Abstract 5434: Functional screening for impact on cancer hallmarks migration, transformation and angiogenesis identifies potential new drug leads isolated from marine organisms
Authors: Jan E. Ehlert, Holger Weber, Melanie Mueller, Oliver Siedentopf, Wenhan Lin, Peter Proksch, Michael HG Kubbutat
Journal: Cancer Research (2011)

Abstract Marine organisms represent a potential new source for lead compounds applicable for cancer therapy. Traditionally, natural sources have been in the focus of drug discovery and have so far yielded an impressive number of drugs that are indispensable in modern therapy. About two thirds of all anti-cancer drugs approved today are in fact either natural products or have been developed on the basis of knowledge gained from natural products. This is especially pronounced in the field of cancer chemotherapy. Of special interest to us were compounds from so far under-explored and under-exploited marine organisms from China and Vietnam. In this study compounds from such organisms have been isolated and analysed in phenotypic cellular assays for their inhibitory impact on critical hallmarks of cancer. For that purpose, we have developed medium throughput phenotypic assays to look at transformation, angiogenesis and migration, indicated by soft agar growth, endothelial sprouting and wound healing, respectively. We report on a phenotypic screen of 160 compounds derived from marine organisms, which lead to the identification of several differentially inhibitory substances which are subsequently analysed in detail. This project was funded by the German ministry of Science and Education; Grant No 0315322. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5434. doi:10.1158/1538-7445.AM2011-5434