tbuckley/cabot-search huggingface dataset:
β-BLOCKER THERAPY IS NOT ASSOCIATED WITH REDUCTIONS IN ANGINA OR CARDIOVASCULAR EVENTS AFTER CORONARY ARTERY BYPASS GRAFT SURGERY
Authors: Harmen Govert Booij, Kevin Damman, Wayne J. Warnica, Richard Baillot, Jean L. Rouleau, Wiek H. van Gilst, B. Daan Westenbrink
Journal: Journal of the American College of Cardiology (2014)
Protective Role of Uncoupling Protein 2 in Atherosclerosis
Authors: J. Blanc, M.C. Alves-Guerra, B. Esposito, S. Rousset, P. Gourdy, D. Ricquier, A. Tedgui, B. Miroux, Z. Mallat
Journal: Circulation (2003)

Background— Uncoupling protein 2 (UCP2) regulates the production of reactive oxygen species in macrophages. However, its role in atherosclerosis is unknown. Methods and Results— Irradiated low-density lipoprotein receptor deficient mice (LDLR-/-) were transplanted with bone marrow from either UCP2 deficient mice ( Ucp2 -/-) or wild type mice ( Ucp2 +/+). Mice were fed an atherogenic diet for 7 weeks. Engraftment of bone marrow cells was confirmed by the presence of UCP2 protein expression in spleen cell mitochondria of Ucp2 +/+ transplanted mice and its absence in Ucp2 -/- transplanted mice. Leukocyte counts and plasma cholesterol levels were comparable in both groups. We found a marked increase in atherosclerotic lesion size in the thoracic aorta of Ucp2 -/- transplanted mice compared with control Ucp2 +/+ transplanted mice (8.3±0.9% versus 4.3±0.4%, respectively; P &lt;0.005), as well as in the aortic sinus (150 066±12 388 μm 2 versus 105 689±9 727 μm 2 , respectively; P &lt;0.05). This was associated with increased nitrotyrosine staining, which suggests enhanced oxidative stress. Analysis of plaque composition revealed a significant increase in macrophage accumulation ( P &lt;0.05) and apoptosis ( P &lt;0.05), along with a decrease in collagen content ( P &lt;0.05), suggesting a potentially more vulnerable phenotype. Conclusion— These results suggest a protective role for UCP2 against atherosclerosis.
Chromatin modifiers and the promise of epigenetic therapy in acute leukemia
Authors: S M Greenblatt, S D Nimer
Journal: Leukemia (2014)

Hematopoiesis is a tightly regulated process involving the control of gene expression that directs the transition from hematopoietic stem and progenitor cells to terminally differentiated blood cells. In leukemia, the processes directing self-renewal, differentiation and progenitor cell expansion are disrupted, leading to the accumulation of immature, non-functioning malignant cells. Insights into these processes have come in stages, based on technological advances in genetic analyses, bioinformatics and biological sciences. The first cytogenetic studies of leukemic cells identified chromosomal translocations that generate oncogenic fusion proteins and most commonly affect regulators of transcription. This was followed by the discovery of recurrent somatic mutations in genes encoding regulators of the signal transduction pathways that control cell proliferation and survival. Recently, studies of global changes in methylation and gene expression have led to the understanding that the output of transcriptional regulators and the proliferative signaling pathways are ultimately influenced by chromatin structure. Candidate gene, whole-genome and whole-exome sequencing studies have identified recurrent somatic mutations in genes encoding epigenetic modifiers in both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). In contrast to the two-hit model of leukemogenesis, emerging evidence suggests that these epigenetic modifiers represent a class of mutations that are critical to the development of leukemia and affect the regulation of various other oncogenic pathways. In this review, we discuss the range of recurrent, somatic mutations in epigenetic modifiers found in leukemia and how these modifiers relate to the classical leukemogenic pathways that lead to impaired cell differentiation and aberrant self-renewal and proliferation.
The density of epidermal p53 clones is higher adjacent to squamous cell carcinoma in comparison with basal cell carcinoma
Authors: H. Backvall, O. Wolf, H. Hermelin, E. Weitzberg, F. Ponten
Journal: British Journal of Dermatology (2004)

Background It is well accepted that ultraviolet radiation from the sun can induce and promote growth of skin tumours. Skin cancer develops as a consequence of multiple genetic hits, where an initial, important step includes proliferation of cells susceptible to malignant transformation. Foci of morphologically normal epidermal keratinocytes overexpressing p53 protein are common in chronically sun‐exposed skin. Such foci have previously been shown to represent expanding clones of p53‐mutated keratinocytes. Although several characteristics concerning epidermal p53 clones remain to be resolved, an important role in skin carcinogenesis is anticipated. The density of epidermal p53 clones in human skin is largely unknown. Objectives To compare the occurrence of epidermal p53 clones in skin surrounding cancers with that in skin surrounding benign melanocytic naevi. To assess the influence of age on frequency and size of epidermal p53 clones in human facial skin. Methods We have analysed the number and sizes of epidermal p53 clones in skin specimens from patients with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and benign melanocytic naevi. Cases included normal facial skin from four different age groups. Tissue sections were immunohistochemically stained and the presence of p53 clones was recorded. Approximately 1·4 m of epidermis from a total of 112 biopsies was analysed. Results We found 128 epidermal p53 clones in biopsy specimens from 112 patients. The results showed that the number and size of p53 clones increase with age. In normal skin adjacent to SCC p53 clones were significantly more numerous and greater in size in comparison with those in normal skin both adjacent to benign naevi and adjacent to BCC. Interestingly, normal skin in the close vicinity of BCC and melanocytic naevi showed similar results regarding both number and size of epidermal p53 clones. Conclusions Our findings suggest a connection between development of epidermal p53 clones and SCC.
Pre-Explant Stability of Unloading-Promoted Cardiac Improvement Predicts Outcome After Weaning From Ventricular Assist Devices
Authors: Michael Dandel, Yuguo Weng, Henryk Siniawski, Evgenij Potapov, Thomas Krabatsch, Hans B. Lehmkuhl, Thorsten Drews, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2012)

Background— Detection of cardiac recovery that allows long-term cardiac stability after ventricular assist device (VAD) explantation is a major goal. After normalization of ventricular diameters during unloading, the pre-explant left ventricular ejection fraction (LVEF) allows the detection of patients with the potential to remain stable after VAD explantation. However, some patients with LVEF &gt;45 before VAD explantation show early recurrence of heart failure (HF). We aimed to find out if unstable improvement can be recognized before VAD explantation. Methods and Results— Among 96 patients weaned from VADs since 1995, a relatively homogenous group of 53 patients with nonischemic chronic cardiomyopathy (CCM) was selected for the study. The pre-explant stability of major parameters of LV function, size, and geometry that were measured by echocardiography during serial “off-pump” trials was tested for relationship with cardiac stability after VAD explantation. LVEF, systolic peak wall motion velocity (Sm), end-diastolic diameter (LVEDD), end-diastolic relative wall thickness (RWT ED ) and end-diastolic short/long-axis ratio (S/L ED ) were selected for evaluation. In postweaning unstable patients, the selected parameters showed relevant instability already before VAD explantation during the time period between best cardiac improvement and VAD explantation and also during the final off-pump trial just before VAD explantation. For all parameters, there were significant differences ( P &lt;0.05) in pre-explant changes between patients with and without postweaning cardiac stability. Using the optimal cutoff values obtained from receiver-operating characteristic analysis, we found for our selected parameters predictive values for postexplant cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 94 and 100, 92, and 100, and 78 and 100, respectively. Using for all parameter changes the cutoff value of 10, we found similar predictive values for cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 93 and 97, 90 and 96, and 83 and 92, respectively. Conclusions— Our results strongly suggest the possibility to improve the prediction of postexplant transplant/VAD-free outcome in CCM patients with cardiac improvement during VAD support by analyzing the pre-explant stability of several LV off-pump echocardiographic parameters during serial off-pump trials.
Genetic susceptibility in ecosystems: the challenge for ecotoxicology.
Authors: A J Evenden, M H Depledge
Journal: Environmental Health Perspectives (1997)

Environmental management is inevitably complicated by the large variation in susceptibility to chemical toxicity exhibited by the living components of ecosystems, a significant proportion of which is determined by genetic factors. This paper examines the concept of genetic susceptibility in ecosystems and suggests the existence of two distinct forms reflecting genetic changes at the level of the individual and at the level of population and community. The influence of genetic susceptibility on exposure-response curves is discussed and the consequent accuracy of data used for toxicity test-based risk assessments examined. The paper concludes by describing a possible biomarker-based approach to future studies of susceptibility in ecosystems, suggesting the use of modern molecular genetic methods.
Update on Prevention of Malaria for Travelers
Authors: Hans O. Lobel
Journal: JAMA (1997)

Individuals from industrialized nations frequently travel to countries with malaria, so health care providers need to be familiar with current recommendations for prevention of malaria. Changes in drug susceptibility of malaria parasites and evolving knowledge of how well drugs are tolerated necessitate periodic review of guidelines for prophylaxis of malaria, especially of chloroquine-resistant<i>Plasmodium falciparum</i>malaria. Mefloquine is the drug of choice for chemoprophylaxis for most travelers, with doxycycline and chloroquine being less effective alternatives. Mefloquine is well tolerated at prophylactic dosages, but anecdotal reports have raised concerns about its adverse effects. Resistance to this drug has emerged in parts of Southeast Asia and may spread to other regions of the world. The major disadvantages of doxycycline are the need for daily dosing, its contraindication for young children and pregnant women, and its adverse effects. Chloroquine is effective for prophylaxis only in Central America, the Caribbean, and parts of the Middle East. Few new drugs will be available in the near future because of reduced funding for antimalarial drug research and development; therefore, the usefulness of currently available drugs needs to be prolonged by rational use. Increased efforts should be made to ensure that alternative drugs will be available for prevention of malaria.
Transporters involved in the hepatic uptake of 99mTc-mebrofenin and indocyanine green
Authors: Wilmar de Graaf, Stephanie Häusler, Michal Heger, Tessa M. van Ginhoven, Gert van Cappellen, Roelof J. Bennink, Gerd A. Kullak-Ublick, Rolf Hesselmann, Thomas M. van Gulik, Bruno Stieger
Journal: Journal of Hepatology (2010)
Assessment of the elicitation response in subjects weakly sensitized to<i>p</i>-phenylenediamine
Authors: L.M. Pot, P.J. Coenraads, C. Goebel, B. Blömeke
Journal: British Journal of Dermatology (2014)

A 30-min application of a hair dye product containing 2% p-phenylenediamine (PPD) to subjects diagnostically graded +, showed that 12 of 18 reacted; eight of 18 with a true + and four of 18 with a doubtful (?+) response, whereas six of 18 did not react at all. In vitro skin-binding experiments showed that for diagnostic patch test conditions the measured exposure level (MEL) is more than 10-fold higher than the MEL for hair dyeing conditions.To further analyse the limited elicitation response of the diagnostically + graded subjects to a PPD hair dye product, under standardized test conditions mimicking product usage, by varying exposure time and dose.A hair dye model formulation containing 2% PPD, applied for 30, 45 and 60 min and a diagnostic PPD TRUE test(®) were applied to assess elicitation responses to increasing PPD exposure levels. Grading was performed according to International Contact Dermatitis Research Group guidelines.Six subjects were available for this follow-up study. One of six subjects responded with a + elicitation response to the hair dye model applied for 60 min. Four of the five remaining subjects elicited a + response to the PPD TRUE test(®) applied subsequently, while one of five responded doubtfully.Increasing the PPD exposure time twofold--resulting in a 5-6% increase of sensitivity of this hair dye model test--or further extending the exposure time 48-fold, was found sufficient to increase the MEL above the thresholds needed to elicit individuals with a + diagnostic PPD patch test who did not react to typical hair dye use conditions with a MEL of about 6·8 μg cm⁻². This analysis confirms that consideration of the MEL is a useful tool to better characterize thresholds of elicitation than consideration of the applied dose alone.
Best research: Research originating in primary care needs support
Authors: Jim Sikorski, Susan Robinson, Martin Edwards
Journal: BMJ (2006)

Case reports of suspected adverse drug reactions Case reports were dismissed too quicklyEditor-The main difference between the replications by Loke et al of Venning's studies from the 1980s and the original is the evidence that is accepted as further follow-up. 1 Loke et al mention that 56 of 63 case reports on adverse reactions were cited at least once but accept only nine instances as valid follow-up: attempts at proof of mechanisms or controlled studies.However, unexpected adverse effects are by definition due to an unknown mechanism, and many established adverse effects still escape elucidation after years.Moreover, further accumulation of anecdotal reports can be sufficient evidence.A 10 year tally of 22 drugs that were withdrawn from the market showed that 18 were prompted by case reports and only four by a controlled study; for at least 13 the case reports proved sufficient reason for withdrawal. 2 A highly unusual event that is repeatedly reported in a recently marketed drug, in the absence of publicity, points to an exceedingly high relative risk, a good argument for cause and effect. 3 Moreover, these risks will be picked up spontaneously. 4 5 Apart from the nine instances of follow-up that were accepted by Loke et al, 15 datasheets were amended and seven BNP drug monographs changed.So, even with some overlap, close to half of the case reports were somehow sufficiently noteworthy to have had consequences.Given the small sample size, this is not far from Venning's original.It is a pity that Loke et al do not make all follow-up more explicit for all 56 instances that followed the 63 reports.Their overall conclusion that lack of follow-up means that case reports are of limited value is a non-sequitur.It shows that a more consistent scheme of hypothesistesting studies by industry, government, or third parties is needed instead of the current haphazard approach to drug safety.Such publications may alert and help clinicians in recognising potential adverse events in their patients.Often there is no other way of discovering something unusual.The record of systematic-that is, controlledpostmarketing surveillance in detecting unexpected adverse effects remains surprisingly poor.
Seasonal trends in childhood asthma.
Authors: J S Ashley
Journal: BMJ (1983)

Dr White's point about the validity of a prospective survey which gave "in progress" feedback is logically quite correct.Rebutting his assertion, however, we believe that the failure to change despite feedback is the case with peer review.There is evidence that aspects of doctor behaviour are peculiar to the individual doctor.'Work in relation to quality of care and peer review begins to show that, unless doctors who review their work generate their own objectives and do so with a commitment to themselves and their peers, appreciable change is unlikely.2Our findings support these observations.We therefore feel that our study is valid and that our examination of the hypothesis was not impaired.
Endoscopic Access to the Papilla of Vater for Endoscopic Retrograde Cholangiopancreatography in Patients with Billroth II or Roux-en-Y Gastrojejunostomy
Authors: R. E. Hintze, A. Adler, W. Veltzke, H. Abou-Rebyeh
Journal: Endoscopy (1997)

Background and Study Aims: Endoscopic retrograde cholangiopancreatography (ERCP) is an established modality for the diagnosis and treatment of pancreaticobiliary disorders. In contrast to ERCP in patients who have not undergone gastrectomy, ERCP in patients with a Billroth II gastrojejunostomy or a Roux-en-Y anastomosis is considerably more difficult. It was nevertheless considered that ERCP might be possible in most patients with gastrectomies, and this hypothesis was tested.
FILTRATION OF PUBLIC WATER SUPPLIES.
Authors: HARRY W. CLARK
Journal: JAMA (1907)

The purification of municipal water supplies by filtration has been practiced for over seventy years. Apparently the first filter of considerable size was that constructed by the city of London in 1829, and that city now has about 120 acres of sand filter beds. Berlin, Germany, built water works and sand filters in 1856, fifty years ago, and at the present time practically all the important cities of Great Britain and Germany filter their water supply if this water is taken from a surface source. Filtration of public supplies is widely practiced in other countries, especially Belgium and Holland. Even Russia has several large municipal filters; a recent article in the<i>Engineering Record</i>describes large sand filtration plants in Japan, while in India and Egypt a number of large municipal supplies are treated by mechanical filters. The first large municipal filter in America was constructed at Lawrence, Mass., in 1892-93,
Coordination of fibronectin adhesion with contraction and relaxation in microvascular smooth muscle
Authors: Zhongkui Hong, Zhe Sun, Zhaohui Li, Walatta-Tseyon Mesquitta, Jerome P. Trzeciakowski, Gerald A. Meininger
Journal: Cardiovascular Research (2012)

AimsThe regulation of vascular diameter by vasoconstrictors and vasodilators requires that vascular smooth muscle cells (VSMCs) be physically coupled to extracellular matrix (ECM) and neighbouring cells in order for a vessel to mechanically function and transfer force. The hypothesis was tested that integrin-mediated adhesion to the ECM is dynamically up-regulated in VSMCs during contractile activation in response to a vasoconstrictor and likewise down-regulated during relaxation in response to a vasodilator.
Integration of woodchuck hepatitis and N-myc rearrangement determine size and histologic grade of hepatic tumors
Authors: James R. Jacob, Agnes Sterczer, Ilia A. Toshkov, Amy E. Yeager, Brent E. Korba, Paul J. Cote, Marie-Annick Buendia, John L. Gerin, Bud C. Tennant
Journal: Hepatology (2004)

Integrations of woodchuck hepatitis virus (WHV) DNA and rearrangements of the N-myc 2 gene have been detected frequently in hepatocellular carcinoma (HCC) of Eastern woodchucks ( Marmota monax ) chronically infected with WHV. Fifty-five hepatocellular neoplasms and matched nontumor hepatic tissue specimens obtained postmortem from 13 chronic WHV carriers were analyzed and the frequency of WHV DNA integrations and of N-myc rearrangements compared in tumors of different size and histologic grade. Four small tumor nodules were classified histologically as adenomas and integrated sequences of WHV DNA were detected in two of the four tumor nodules. In one of the two nodules, there was evidence of N-myc rearrangement. Fifty-one neoplasms were classified as HCC. Seven were grade 1 HCCs. WHV DNA integrations were demonstrated in 43% but none had N-myc rearrangements. Twenty grade 2 HCCs had WHV DNA integrations in 80% and in 38% N-myc rearrangements were present. Twenty-four grade 3 HCCs had integrations of WHV DNA in 79% and N-myc rearrangements in 74%. In two other grade 3 HCCs, rearrangements of N-myc were detected in the absence of WHV DNA integrations. The 12 largest tumors in the series all were grade 2 or 3 HCCs, and in 83%, both WHV DNA integrations and N-myc rearrangements were demonstrated. In conclusion, molecular changes observed in this study suggest a progression of genetic alterations providing either a significant proliferative stimulation and/or a growth advantage in hepatocarcinogenesis of woodchucks with chronic WHV infection. (Hepatology 2004;39:1008-1016.)
Therapy for Adults with Refractory Chronic Immune Thrombocytopenic Purpura
Authors: Robert McMillan
Journal: Annals of Internal Medicine (1997)

Adult chronic immune thrombocytopenic purpura (ITP) is a common hematologic disorder; about 14 000 to 16 000 new cases occur each year in the United States.Initial treatment with corticosteroids and splenectomy results in normal or "safe" platelet counts in more than 70% of patients. Treatment of patients refractory to these two treatments is difficult. This paper describes a structured approach to therapy that is based on a literature review and personal experience, including experience with treatment of chronic ITP in special situations (such as emergent bleeding, pregnancy, and central nervous system bleeding). Treatment of most patients with chronic ITP is fairly straightforward, but management of patients refractory to corticosteroids and splenectomy can be difficult. Large, randomized studies are clearly needed to better evaluate the many types of treatment that are recommended for refractory patients.
Lehrbuch der Gerichtlichen Medizin für Mediziner und Juristen
Authors: S. M. Rabson
Journal: JAMA (1967)

<b>Homicide Investigation: Practical Information for Coroners, Police Officers, and Other Investigators</b>, by LeMoyne Snyder, ed 2; 394 pp, 164 illus, $14, Springfield, Ill: Charles C Thomas, Publisher, 1967. Now that "American" is the lingua franca, practitioners of laboratory medicine in this country may not hurry to buy such a work as Ponsold's textbook of legal medicine. Like British works on medical jurisprudence, it devotes a large, first section to national laws governing medical practice and includes such chapters as delinquencies of behavior and the psychology of witnesses. The main body of the work, however, by more than 30 collaborators, deals with problems in medicolegal practice—anatomic, serologic, toxicologic. Even to those for whom German is truly a foreign language, one feature is highly commendable. Instead of the usual collection of good or bad photographs of hangings, stabbings, and the like, productive of horror and little else in the reader, diagrammatic drawings