tbuckley/cabot-search huggingface dataset:
Dissecting Inflammatory Complications in Critically Injured Patients by Within-Patient Gene Expression Changes: A Longitudinal Clinical Genomics Study
Authors: Keyur H. Desai, Chuen Seng Tan, Jeffrey T. Leek, Ronald V. Maier, Ronald G. Tompkins, John D. Storey
Journal: PLoS Medicine (2011)

Background Trauma is the number one killer of individuals 1–44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition. Methods and Findings We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40–80 h window post-injury. Conclusions The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions. Trial Registration ClinicalTrials.gov NCT00257231 Please see later in the article for the Editors' Summary
Efficacy of the high molecular weight fraction of plasma for the maintenance of pregnancy associated with thrombotic thrombocytopenic purpura
Authors: Tetsuji Koyama, Akira Suehiro, Eizo Kakishita, Shozo Taira, Shinzo Isojima, Mihoko Norioka, Kazuhiko Ito
Journal: American Journal of Hematology (1990)

We have investigated the methods for the maintenance of a pregnancy in a patient with thrombotic thrombocytopenic purpura (TTP), said condition, since 1984, having been controlled by a plasma infusion every 3 to 4 weeks. In a preliminary trial it was confirmed that an infusion of the high molecular weight fraction (HMW-F) of plasma, separated by an Evaflux 2A fractionator, improved the patient's thrombocytopenia as the plasma infusion, and maintained its beneficial effect for about 2 weeks during early pregnancy. Though an occurrence of a toxemia-like syndrome responded to repeated plasma infusion, the dose of plasma required to improve the thrombocytopenia gradually increased and reached 5,040 ml by the 20th week of pregnancy. Thus, instead of periodic infusions of whole plasma, periodic infusions of the HMW-F of plasma were used. Under this regimen the platelet count remained above 10.0 x 10(4)/microliters during late pregnancy, and the total dose (2,600 ml) of HMW-F of plasma that was administered until delivery at full term was less than the dosage of whole plasma that was used during early pregnancy. In this manner we were able to obtain a healthy baby by controlling the patient's TTP during pregnancy. This method of preventing thrombocytopenia appears to be safer with respect to volume loading during pregnancy in the TTP patient.
Flaws in analysis lead to misleading conclusions about varenicline's safety in smoking cessation
Authors: S. Singh, Y. K. Loke
Journal: BMJ (2012)

The meta-analysis by Prochaska and Hilton has several methodological limitations in data analysis and interpretation, which lead to misleading conclusions.1 Despite the removal of cardiovascular events from the trials and a statistical approach that has limited power to detect a significant effect, there is an excess risk of cardiovascular events with varenicline in all five measures reported.

The risk difference model Prochaska and Hilton used is statistically …
Estimating Overdiagnosis in Low-Dose Computed Tomography Screening for Lung Cancer
Authors: Giulia Veronesi, Patrick Maisonneuve, Massimo Bellomi, Cristiano Rampinelli, Iara Durli, Raffaella Bertolotti, Lorenzo Spaggiari
Journal: Annals of Internal Medicine (2012)

Background: Lung cancer screening may detect cancer that will never become symptomatic (overdiagnosis), leading to overtreatment. Changes in size on sequential low-dose computed tomography (LDCT) screening, expressed as volume-doubling time (VDT), may help to distinguish aggressive cancer from cases that are unlikely to become symptomatic. Objective: To assess VDT for screening-detected lung cancer as an indicator of overdiagnosis. Design: Retrospective estimation of the VDT of cancer detected in a prospective LDCT screening cohort. Setting: Nonrandomized, single-center screening study involving persons at high risk for lung cancer enrolled between 2004 and 2005 who received LDCT annually for 5 years. Patients: 175 study patients diagnosed with primary lung cancer. Measurements: VDT was measured on LDCT and classified as fast-growing (<400 days), slow-growing (between 400 and 599 days), or indolent (≥600 days). Results: Fifty-five cases of cancer were diagnosed at baseline, and 120 were diagnosed subsequently. Of the latter group, 19 cases (15.8%) were new (not visible on previous scans) and fast-growing (median VDT, 52 days); 101 (84.2%) were progressive, including 70 (58.3%) fast-growing and 31 (25.8%) slow-growing (15.0%) or indolent (10.8%) cases. Lung cancer–specific mortality was significantly higher (9.2% per year) in patients with new compared with slow-growing or indolent (0.9% per year) cancer. Sixty percent of fast-growing progressive cancer and 45% of new cancer were stage I, for which survival was good. Limitations: This is a retrospective study. Volume-doubling time can only indicate overdiagnosis and was estimated for new cancer from 1 measurement (a diameter of 2 mm assumed the previous year). Conclusion: Slow-growing or indolent cancer comprised approximately 25% of incident cases, many of which may have been overdiagnosed. To limit overtreatment in these cases, minimally invasive limited resection and nonsurgical treatments should be investigated. Primary Funding Source: Italian Association for Cancer Research.
Cooperative Study of Hospital Frequency and Character of Transient Ischemic Attacks
Authors: Philip R. Calanchini
Journal: JAMA (1977)

All patients (1,328) suspected of having transient ischemic attacks (TIA) who came to six institutions over a 21-months period were identified. Each case was reviewed by a neurological investigator, and a definite diagnosis of TIA was supported in 39% and ruled out in 30%. The reliability of the neurologist's review diagnosis was assessed by three methods, and close agreement (84% to 93%) was obtained. Factors demonstrated to effect the diagnosis were historical information, neurological training of the examiners, type of symptom complex, presence of carotid artery bruits, and examination during an attack.
Sensorineural hearing loss in adult onset Still's disease.
Authors: H M Markusse, B Stolk, A G van der Mey, J M de Jonge-Bok, K J Heering
Journal: Annals of the Rheumatic Diseases (1988)

A 26 year old man with a nine year history of adult onset Still9s disease (AOSD) developed sensorineural hearing loss during an exacerbation of his disease. This complication has not previously been described in association with adult onset Still9s disease. He responded favourably to steroid treatment.
Tip60 Protein Isoforms and Altered Function in Skin and Tumors that Overexpress Ornithine Decarboxylase
Authors: Cheryl A. Hobbs, Gang Wei, Karen DeFeo, Barry Paul, Candace S. Hayes, Susan K. Gilmour
Journal: Cancer Research (2006)

Abstract Elevated expression of ornithine decarboxylase (ODC) and increased synthesis of polyamines are hallmarks of epithelial tumorigenesis. The skin and tumors of K6/ODC and ODC/Ras transgenic mice, in which overexpression of ODC has been targeted to hair follicles, were found to exhibit intrinsically high histone acetyltransferase (HAT) activity. We identified Tip60 as a candidate enzyme for contributing significantly to this abnormally high HAT activity. Compared with normal littermate controls, the levels of Tip60 protein and an alternative splice variant Tip53 were found to be greater in K6/ODC mouse skin. Furthermore, skin tumors that spontaneously develop in ODC/Ras bigenic mice typically have substantially more Tip60 protein than adjacent non–tumor-bearing skin and exhibit a unique pattern of Tip60 size variants and chemically modified protein isoforms. Steady-state Tip60 and Tip53 mRNA levels were not affected in ODC-overexpressing skin and tumors, implying novel posttranscriptional regulation by polyamines. Given the diverse roles of Tip60, the overabundance of Tip60 protein is predicted to have biological consequences. Compared with normal littermate skin, we detected altered association of Tip60 with E2F1 and a subset of newly identified Tip60-interacting transcription factors in ODC transgenic mouse skin and tumors. E2F1 was shown to be bound in greater amounts to up-regulated target genes in ODC-overexpressing skin. Thus, up-regulation of Tip60 protein, influencing the expression of Tip60-regulated genes, could play a contributing role in polyamine-mediated tumor promotion. (Cancer Res 2006; 66(16): 8116-22)
Fibronectin in fulminant hepatic failure.
Authors: J Gonzalez-Calvin, M F Scully, Y Sanger, J Fok, V V Kakkar, R D Hughes, A E Gimson, R Williams
Journal: BMJ (1982)

Thirteen out of 17 patients with fulminant hepatic failure had plasma fibronectin concentrations below the normal range (194--472 micrograms/ml), the mean concentration in all 17 patients being 117.9 +/- SE 19.4 micrograms/ml. There was a significant negative correlation between plasma fibronectin concentration and aspartate aminotransferase activity, suggesting that fibronectin is consumed during clearance of hepatocyte debris. The reduced availability of fibronectin may be an important factor in the impaired function of Kuppfer cells in patients with fulminant hepatic failure.
Cancer Screening in the United States, 2007: A Review of Current Guidelines, Practices, and Prospects
Authors: R. A. Smith, V. Cokkinides, H. J. Eyre
Journal: CA A Cancer Journal for Clinicians (2007)

Each year, the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, including guideline updates, emerging issues that are relevant to screening for cancer, and a summary of the most current data on cancer screening rates for US adults. In 2006, there were no updates to ACS guidelines for early cancer detection. In this issue of the journal, we describe criteria for successful screening, discuss recent evidence and policy changes that have implications for cancer screening, summarize the ACS guidelines and describe guidelines reviews that are underway, and provide an update of the most recent data pertaining to participation rates in cancer screening from the Centers for Disease Control and Prevention's (CDC's) Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS).
CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients
Authors: N Hosen, Y Matsuoka, S Kishida, J Nakata, Y Mizutani, K Hasegawa, A Mugitani, H Ichihara, Y Aoyama, S Nishida, A Tsuboi, F Fujiki, N Tatsumi, H Nakajima, M Hino, T Kimura, K Yata, M Abe, Y Oka, Y Oji, A Kumanogoh, H Sugiyama
Journal: Leukemia (2012)
Pathologies of Power: Health, Human Rights, and the New War on the Poor
Authors: B. L Lichterman
Journal: BMJ (2003)

I was once lucky enough to meet and correspond with Dr Roy Selby (1930-2002), a retired neurosurgeon from Texarkana, Texas. In the 1960s Dr Selby spent seven years in Malaysia, where he built the country's first hospital for neurosurgery. He wrote in one of his last letters: “I discussed with the US ambassador at the time the possibility of the Dept of State providing aid to establish a new medical school, utilising Malaysian personnel. He said something like, ‘Hell, if we do it we'll do the whole thing.’ That is how our government destroys so many overseas ventures—not supporting or [not] allowing the local people to run things. This is another form of aggression.”

   ![][1] 

Paul Farmer 

University of California Press, £18.95/$27.50, pp 402

ISBN 0520235509

Rating: ![Graphic][2] ![Graphic][3] ![Graphic][4] 

Dr Selby would certainly have enjoyed this book by Paul Farmer, a professor of medical anthropology at Harvard Medical School and founding director of Partners in Health, a non-governmental organisation “created to remediate inequalities in access to modern health care.” Farmer and his colleagues set up a …

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Interaction of MLL Amino Terminal Sequences with Menin Is Required for Transformation
Authors: Corrado Caslini, Zhaohai Yang, Mohamad El-Osta, Thomas A. Milne, Robert K. Slany, Jay L. Hess
Journal: Cancer Research (2007)

Abstract Rearrangements of the mixed lineage leukemia gene MLL are associated with aggressive lymphoid and myeloid leukemias. The resulting MLL fusion proteins enforce high-level expression of HOX genes and the HOX cofactor MEIS1, which is pivotal for leukemogenesis. Both wild-type MLL and MLL fusion proteins interact with the tumor suppressor menin and with the Hoxa9 locus in vivo. Here, we show that MLL sequences between amino acids 5 and 44 are required for interaction with menin and for the transformation of hematopoietic progenitors. Blocking the MLL-menin interaction by the expression of a dominant negative inhibitor composed of amino terminal MLL sequences down-regulates Meis1 expression and inhibits cell proliferation, suggesting that targeting this interaction may be an effective therapeutic strategy for leukemias with MLL rearrangements. [Cancer Res 2007;67(15):7275–83]
Paradoxical Pulsus Paradoxus
Authors: Samuel Vaisrub
Journal: JAMA (1974)

In a report published in the<i>Archives of Internal Medicine</i>half a century ago, Katz and Gauchat<sup>1</sup>called attention to the nonparadoxical nature of pulsus paradoxus. They pointed out that the rhythmical diminution of the pulse and blood pressure on inspiration, which Kussmaul described 50 years previously as a characteristic of chronic cardiac compression, is<i>not</i>a paradoxical phenomenon but an exaggeration of the normal response. The blood pressure in the normal individual also drops on inspiration, but the fall of the systolic peak never exceeds 5 mm Hg. By contrast, in the pathologic "paradoxical" pulse, the fall is greater than 10 mm Hg. The mechanism of the normal phenomenon probably reflects an imbalance between the outputs of the right and left ventricles. Reduced intrapleural and intrathoracic pressures on inspiration result in augmented venous return to the right atrium and thus an increased right ventricular volume. The simultaneous pooling
The LIM Homeobox Gene ceh-14 Confers Thermosensory Function to the AFD Neurons in Caenorhabditis elegans
Authors: Giuseppe Cassata, Hiroshi Kagoshima, Yoshiki Andachi, Yuji Kohara, Markus B. Dürrenberger, David H. Hall, Thomas R. Bürglin
Journal: Neuron (2000)
In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transfer
Authors: Oumeya Adjali, Gilles Marodon, Marcos Steinberg, Cédric Mongellaz, Véronique Thomas-Vaslin, Chantal Jacquet, Naomi Taylor, David Klatzmann
Journal: Journal of Clinical Investigation (2005)

SCID patients have been successfully treated by administration of ex vivo gene-corrected stem cells. However, despite its proven efficacy, such treatment carries specific risks and difficulties. We hypothesized that some of these drawbacks may be overcome by in situ gene correction of T lymphoid progenitors in the thymus. Indeed, in vivo intrathymic transfer of a gene that provides a selective advantage for transduced prothymocytes should result in the generation of functional T lymphocyte progeny, allowing long-term immune reconstitution. We assessed the feasibility of this approach in a murine model of ZAP-70–deficient SCID. A T cell–specific ZAP-70–expressing lentiviral vector was injected into thymi of adult ZAP-70–/– mice without prior conditioning. This resulted in the long-term differentiation of mature TCR-αβ+ thymocytes, indicating that the vector had integrated into progenitor cells. Moreover, peripheral ZAP-70–expressing T cells demonstrated a partially diversified receptor repertoire and were responsive to alloantigens in vitro and in vivo. Improved treatment efficacy was achieved in infant ZAP-70–/– mice, in which the thymus is proportionately larger and a higher percentage of prothymocytes are in cycle. Thus, intrathymic injection of a lentiviral vector could represent a simplified and potentially safer alternative to ex vivo gene-modified hematopoietic stem cell transplantation for gene therapy of T cell immunodeficiencies.
Precut Papillotomy: A Method to Improve Success of ERCP and Papillotomy
Authors: Jerome Siegel
Journal: Endoscopy (1980)

The use of precut papillotomy as an aid to diagnosis with ERCP and an expedient method for endoscopic papillotomy is described. Precut papillotomy enables the experienced endoscopist to increase the successful opacification of the biliary tree in cases in which other techniques have failed, including ERCP, and to initiate a papillotomy or sphincterotomy when the papillotome cannot be introduced completely into the papilla without serious complications. Precut papillotomy is recommended when opacification of the biliary tree or introduction of the papillotome is precluded because of papillary stenosis, impacted calculi or anatomic variations, either natural or acquired, but should only be performed by the endoscopist with experience in both ERCP and papillotomy.
Involvement of a visual blackboard architecture in imagery
Authors: Frank van der Velde, Marc de Kamps
Journal: Behavioral and Brain Sciences (2002)

We discuss a visual blackboard architecture that could be involved in imagery. In this architecture, networks that process identity information interact with networks that process location information, in a manner that produces structural (compositional) forms of representation. Architectures of this kind can be identified in the visual cortex, but perhaps also in prefrontal cortex areas related with working memory.
Japan's Drug Lag Is Longest
Authors: F. S. Antoine
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Japan's Drug Lag Is Longest Get access Florence S. Antoine Florence S. Antoine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 24, 20 December 1989, Page 1866, https://doi.org/10.1093/jnci/81.24.1866 Published: 20 December 1989
Transposition of Viscera
Authors: Wm. J. Mickle
Journal: BMJ (1883)

tbe right in the direction of the umbilicus, but immediately before reaching that point it was again suddenly deflected in the direction of the abdominal cavity, which it unmistakably entered.The most careful examination of the parietes failed to discover the further course of the bullet, and it was considered to have embedded itself in the liver.The worst view of the case was taken, and the patient's friends were sent for.Thirty minims of tincture of opium were at once administered with brandy and water, given in small quantity, and occasionally repeated.Vomiting of a bilious character came on shortly afterwards; and, as the patient suffered severely from the abdominal pain, referred more particularly to the region of the liver,
Gallstones, Gallbladder Cancer, and Other Gastrointestinal Malignancies
Authors: ALBERTO MARINGHINI
Journal: Annals of Internal Medicine (1987)

All 2583 residents of Rochester, Minnesota, who had gallstones initially diagnosed during the years 1950 to 1970 were followed for the development of gastrointestinal malignancies. Although 69 members of the cohort subsequently developed 72 gastrointestinal malignancies, this number of cases did not exceed the 76 cases expected (relative risk, 1.0). The risk for gallbladder cancer was increased threefold, but the increase was significant only in men (p = 0.05; 95% confidence interval, 1.0 to 30.0). The absolute incidence and the total number of men and women who developed gallbladder cancer was low (n = 5). The actual incidence of other gastrointestinal malignancies in our cohort with gallstones did not exceed the expected incidence in the general population of Rochester, Minnesota. Specifically, the risk for colon cancer was not increased, even after cholecystectomy. These data support an association between cholelithiasis and gallbladder cancer. We found, however, no association between cholelithiasis or cholecystectomy and any other gastrointestinal malignancy.
Elevated Cholesteryl Ester Transfer Protein Activity in IDDM Men Who Smoke: Possible Factor for Unfavorable Lipoprotein Profile
Authors: Robin P F Dullaart, Johanna E M Groener, Bert D Dikkeschei, D Willem Erkelens, Hieronymus Doorenbos
Journal: Diabetes Care (1991)

Objectives To determine the effect of cigarette smoking on the activity of cholesteryl ester transfer protein (CETP) and high-density (HDL), low-density (LDL), and very-low-density (VLDL) lipoproteins in insulindependent diabetic (IDDM) men with microvascular complications. Research Design and Methods We perfomed a case-control study in a referral-based diabetes clinic on a sequential sample of 9 cigarettesmoking and 12 nonsmoking IDDM men with microvascular complications and 12 nonsmoking control men. CETP activity was determined in each serum with an isotope assay with exogenous cholesteryl esterlabeled LDL and HDL. The method is independent of the endogenous lipoprotein present in serum. Results The HDL-cholesterol (VLDL and LDL) ratio was lower in the smoking diabetic men than in the other groups (P &amp;lt; 0.05 vs. the nonsmoking diabetic men and P &amp;lt;0.01 vs. the control subjects). CETP activity was 70% higher in the smoking diabetic men than in the control subjects (P &amp;lt;0.01) and 30% higher than in the nonsmoking diabetic men (P &amp;lt;0.05). The HDL-cholesterol (VLDL and LDL) ratio and the apolipoprotein A-l-B ratio were inversely correlated to CETP activity in the diabetic patients (r = −0.52, P &amp;lt;0.02 and r = −0.45, P &amp;lt;0.05, respectively). Conclusions CETP activity is increased in cigarette-smoking IDDM men with microvascular complications. High CETP activity may contribute to the unfavorable lipoprotein profile in these patients.
Primary Hemangioendothelioma of the Liver in Infancy
Authors: S. W. Berezin, J. G. Sharnoff, J. D. Stein
Journal: New England Journal of Medicine (1948)

PRIMARY hemangioendothelioma of the liver in infancy is a rare disease as indicated by a review of the literature. In 1933 Kunstadter1 reported 14 cases, reviewing 13 cases collected from the literature and adding 1 that had come under his observation. Since then Schumann,2 in 1941, reported 2 additional cases, the first in a six-week-old infant and the second in a thirty-six-hour-old male infant who died of cerebral hemorrhage after delivery. Blauel3 added 3 cases to the literature —1 in an infant and 2 in children.Foote4 believed that these tumors were peculiar only to infancy. However, they may occur . . .