tbuckley/cabot-search huggingface dataset:
Cardiac Allograft Vascular Disease
Authors: Mario C. Deng, Steven Bell, Philip Huie, Fausto Pinto, Sharon A. Hunt, Edward B. Stinson, Richard Sibley, Bruce M. Hall, Hannah A. Valantine
Journal: Circulation (1995)

Background Cardiac allograft vascular disease is characterized by accelerated and diffuse intimal proliferation involving both the microvasculature and epicardial vessels. Because in vivo documentation of this complication is now possible with intracoronary ultrasound imaging, we can examine the relationship of intimal proliferation to markers of immunity and endothelial activation. We hypothesize that alterations of microvascular cell surface markers likely mirror changes in the epicardial vessels that may be important in the pathophysiology of intimal proliferation. Methods and Results Forty-three heart transplant patients were examined by intracoronary ultrasound more than 1 year after transplantation, and these images were analyzed to obtain mean intimal thickness and intimal thickness class (I through IV), calculated from the mean thickness and circumferential involvement. Right ventricular endomyocardial biopsies obtained at the time of intracoronary ultrasound were examined by immunohistochemistry to detect microvascular expression of histocompatibility leukocyte antigen (HLA) classes I and II (HLA ABC, DR, DP, and DQ); endothelial-specific antigen detected by the monoclonal antibody E 1.5; intercellular adhesion molecules (ICAM-1); CD4 + and CD8 + lymphocytes and macrophages (CD 14 + ). Microvascular antigen expression was graded 1 through 5 on the basis of the diffuseness of positive staining. The number of each inflammatory cell phenotype present per high-power field was counted. By ANOVA, scores for HLA DR, HLA DQ, and E1.5 expression were lower in intimal thickness classes II, III, and IV compared with class I. This inverse relationship was significant by linear regression analysis of mean intimal thickness. Inflammatory cells were not significantly correlated with intimal thickening. Rejection incidence was higher, and time since transplantation longer, in intimal thickness classes II, III, and IV compared with class I. Conclusion Transplant coronary artery intimal proliferation is associated with alteration of microvascular endothelial cell surface markers. These changes in cell surface antigen expression could provide the substrate for coronary artery intimal proliferation and narrowing.
Diagnostic and prognostic significance of exercise-induced premature ventricular complexes in men and women: A four year follow-up
Authors: Chandra K. Nair, Wilbert S. Aronow, Michael H. Sketch, Tom Pagano, Joseph D. Lynch, Aryan N. Mooss, Dennis Esterbrooks, Vincent Runco, Kay Ryschon
Journal: Journal of the American College of Cardiology (1983)
A Retrospective Analysis of Neutropenia in Patients Receiving Concomitant Administration of Docetaxel and Clarithromycin
Authors: M. Kamezato, D. Tsuji, T. Daimon, K. Taku, M. Hatori, M. Ikeda, H. Hayashi, K. Inoue, T. Eto, K. Itoh
Journal: Annals of Oncology (2013)
Thrombocytopenia and Leukopenia Associated with Itraconazole
Authors: H.A. Horst
Journal: Annals of Internal Medicine (1996)

Letters15 July 1996Thrombocytopenia and Leukopenia Associated with ItraconazoleH.A. Horst, MD, R. Parwaresch, MD, and H. Loffler, MDH.A. Horst, MDUniversity of Kiel, Kiel, Germany, R. Parwaresch, MDUniversity of Kiel, Kiel, Germany, and H. Loffler, MDUniversity of Kiel, Kiel, GermanyAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-2-199607150-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Itraconazole is an imidazole derivative that is effective against many clinically important fungal infections, including aspergillosis, candidiasis, cryptococcosis, and histoplasmosis [1]. We report a case of thrombocytopenia and leukopenia associated with the long-term use of itraconazole.A 54-year-old man presented with acute myelogenous leukemia, FAB M4. He was treated with polychemotherapy (6-thioguanine, ara-C, and daunorubicin [TAD] and hexamethylmelamine, adriamycin, and melphalan [HAM]) [2] and achieved complete remission after the first cycle of TAD. Two weeks after receiving HAM, the patient developed fever, and a chest radiograph showed infiltrates suggestive of fungal infection. The patient's clinical condition and ...References1. Sugar AM. Fluconazole and itraconazole: current status and prospects for fungal therapy. Curr Clin Top Infect Dis. 1993; 13:74-98. Google Scholar2. Buchner T, Hiddemann W, Loffler H, et al. Double induction strategy in AML comparing high with standard dose ARA-C. Hematotoxicity and antileukemic efficacy [Abstract]. Blood. 1994; 84(Suppl 1):232a. Google Scholar3. Goodman LS, Gilman A, Rall TW, Nies AS, Taylor P. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed. New York: Pergamon; 1990:1172. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Kiel, Kiel, Germany PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByItraconazole-induced thrombocytopeniaCurrent use of anti-infectives in dermatologyLeukocytopenia after administration of itraconazole. Leukozytopenie nach Itraconazol-BehandlungIntravenous ItraconazoleFluconazole-Induced Agranulocytosis with EosinophiliaPurpuric drug eruption secondary to itraconazoleItraconazole 15 July 1996Volume 125, Issue 2Page: 156-157KeywordsAcute myeloid leukemiaAntifungalsErythropoiesisFeversHistoplasmosisImidazoleMegakaryocytesNeutrophilsPlateletsThorax Issue Published: 15 July 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Hypertrophy and hyperplasia of alveolar type II cells in response to silica and other pulmonary toxicants.
Authors: B E Miller, G E Hook
Journal: Environmental Health Perspectives (1990)

Alveolar Type II cells serve two major functions in the lung, both of which are essential for the preservation of normal lung function. First, Type II cells synthesize and secrete pulmonary surfactant, and second, they function as progenitor cells for maintaining the alveolar epithelium. The Type II cell population of the lung is quite sensitive to the deposition of toxicants in the distal lung, responding in two principal ways. Damage to the Type I epithelium stimulates Type II cells to proliferate and subsequently differentiate to replace the injured Type I cells. Second, a portion of the Type II cell population may become hypertrophic. Both of these events are frequent findings in the diseased or damaged lung. The Type II cell changes are often associated with increases in surfactant pools. In those cases where ultrastructural characteristics of hypertrophic Type II cells were examined, the appearance of these cells was consistent with that of an activated cell type. Alterations in the lamellar body compartment are a common finding in hypertrophic Type II cells, with increases in both lamellar body size and number. It is likely that the hypertrophic, or activated, Type II cells account for the increased levels of surfactant found in the lungs after exposure to a variety of toxic agents. We examined, in detail, Type II cell hyperplasia and hypertrophy induced by silica deposition. Both Type II cell hyperplasia and hypertrophy were prominent responses. The proliferative response led to an approximate doubling of the number of Type II cells in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Lifetime Pesticide Use and Telomere Shortening among Male Pesticide Applicators in the Agricultural Health Study
Authors: Lifang Hou, Gabriella Andreotti, Andrea A. Baccarelli, Sharon Savage, Jane A. Hoppin, Dale P. Sandler, Joseph Barker, Zhong-Zheng Zhu, Mirjam Hoxha, Laura Dioni, Xiao Zhang, Stella Koutros, Laura E. Beane Freeman, Michael C. Alavanja
Journal: Environmental Health Perspectives (2013)

Telomere length (TL) in surrogate tissues may be influenced by environmental exposures.We aimed to determine whether lifetime pesticides use is associated with buccal cell TL.We examined buccal cell TL in relation to lifetime use of 48 pesticides for 1,234 cancer-free white male pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of 57,310 licensed pesticide applicators. Participants provided detailed information on lifetime use of 50 pesticides at enrollment (1993-1997). Buccal cells were collected from 1999 to 2006. Relative telomere length (RTL) was measured using quantitative real-time polymerase chain reaction. We used linear regression modeling to evaluate the associations between specific pesticides and the logarithm of RTL, adjusting for age at buccal cell collection, state of residence, applicator license type, chewing tobacco use, and total lifetime days of all pesticide use.The mean RTL for participants decreased significantly in association with increased lifetime days of pesticide use for alachlor (p = 0.002), 2,4-dichlorophenoxyacetic acid (2,4-D; p = 0.004), metolachlor (p = 0.01), trifluralin (p = 0.05), permethrin (for animal application) (p = 0.02), and toxaphene (p = 0.04). A similar pattern of RTL shortening was observed with the metric lifetime intensity-weighted days of pesticide use. For dichlorodiphenyltrichloroethane (DDT), we observed significant RTL shortening for lifetime intensity-weighted days (p = 0.04), but not for lifetime days of DDT use (p = 0.08). No significant RTL lengthening was observed for any pesticide.Seven pesticides previously associated with cancer risk in the epidemiologic literature were inversely associated with RTL in buccal cell DNA among cancer-free pesticide applicators. Replication of these findings is needed because we cannot rule out chance or fully rule out bias.
The role of oncogenes in chemical carcinogenesis.
Authors: S J Stowers, R R Maronpot, S H Reynolds, M W Anderson
Journal: Environmental Health Perspectives (1987)

Proto-oncogenes are cellular genes that are expressed during normal growth and developmental processes. Altered versions of normal proto-oncogenes have been implicated in the development of human neoplasia. In this report, we show the detection of activated proto-oncogenes in various spontaneous and chemically induced rodent tumors. The majority of activated proto-oncogenes found in these tumors are members of the ras gene family and have been activated by a point mutation. Characterization of the activating mutation may be useful in determining whether this proto-oncogene was activated by direct interaction of the chemical with the DNA. Comparison of activating lesions in spontaneous versus chemically induced tumors should be helpful in determining whether the chemical acts via a genotoxic or a nongenotoxic mechanism. All of this information may be helpful in the assessment of potential carcinogenic hazards of human exposure to chemicals.
Foundation trusts could be divisive, MPs claim
Authors: M. Limb
Journal: BMJ (2003)

Details of the government's plans for foundation hospitals in England, published in December, have failed to allay fears that they might lead to a two tier health service.

Central to the plans and the controversy are the “significant” new freedoms that foundation trusts will enjoy, subject to legislation being passed. These include the ability to borrow money without having to go through the Treasury.

Up to 12 foundation trusts could be operating from spring 2004. Critics, including many Labour MPs and doctors' leaders, fear that the NHS as a whole will suffer from giving an “elite” cadre of providers more licence to expand services and reward staff.

The BMA council last …
BRADYCARDIA (BELOW RATE OF 40) IN ATHLETES, ESPECIALLY IN LONG DISTANCE RUNNERS
Authors: Paul D. White
Journal: JAMA (1942)

<h3>To the Editor:—</h3> A few months ago a letter was sent to me referring to an article in<i>Collier's</i>about mile running as a sport, in which it was stated that Cunningham has a normal pulse rate of 38, whereas Les MacMitchell has a normal pulse rate of 32. As a matter of fact, these heart rates are not as they were actually stated in the article published in<i>Collier's</i>for June 7, 1941 (pages 19 and 48) under the title "Kid Mercury" by Stanley Frank. In that article Dr. George Deaver of the Department of Physical Education at New York University is quoted as saying "The boy (Les MacMitchell) has the amazing heart beat of 38, one of the lowest on record.... Cunningham's heart beat was 40, and I understand Nurmi's was 42. Those fellows will live a long, long time." This occurrence was questioned by the writer, and
232 GAS EXCHANGE AND PULMONARY MICROCIRCULATION ABNORMALITIES IN CIRRHOTIC AND NON-CIRRHOTIC CHRONIC LIVER DISEASE PATIENTS FREE FROM HEPATOPULMONARY SYNDROME
Authors: U. Vespasiani-Gentilucci, S. Scarlata, M.-E. Conte, G. Galati, D. D'Avola, S. Spataro, E. Fiori, C. Mazzarelli, C. Pedone, R. Antonelli-Incalzi, A. Picardi
Journal: Journal of Hepatology (2009)
Colitis-Associated Cancer Is Dependent on the Interplay between the Hemostatic and Inflammatory Systems and Supported by Integrin αMβ2 Engagement of Fibrinogen
Authors: Kris A. Steinbrecher, Netanel A. Horowitz, Elizabeth A. Blevins, Kelley A. Barney, Maureen A. Shaw, Eleana Harmel-Laws, Fred D. Finkelman, Matthew J. Flick, Malinda D. Pinkerton, Kathryn E. Talmage, Keith W. Kombrinck, David P. Witte, Joseph S. Palumbo
Journal: Cancer Research (2010)

A link between colitis and colon cancer is well established, but the mechanisms regulating inflammation in this context are not fully defined. Given substantial evidence that hemostatic system components are powerful modulators of both inflammation and tumor progression, we used gene-targeted mice to directly test the hypothesis that the coagulation factor fibrinogen contributes to colitis-associated colon cancer in mice. This fundamental provisional matrix protein was found to be an important determinant of colon cancer. Fibrinogen deficiency resulted in a dramatic diminution in the number of colonic adenomas formed following azoxymethane/dextran sodium sulfate challenge. More detailed analyses in mice expressing a mutant form of fibrinogen that retains clotting function, but lacks the leukocyte integrin receptor alpha(M)beta(2) binding motif (Fibgamma(390-396A)), revealed that alpha(M)beta(2)-mediated engagement of fibrin(ogen) is mechanistically coupled to local inflammatory processes (e.g., interleukin-6 elaboration) and epithelial alterations that contribute to adenoma formation. Consistent with these findings, the majority of Fibgamma(390-396A) mice developed no discernable adenomas, whereas penetrance was 100% in controls. Furthermore, the adenomas harvested from Fibgamma(390-396A) mice were significantly smaller than those from control mice and less proliferative based on quantitative analyses of mitotic indices, suggesting an additional role for fibrin(ogen) in the growth of established adenomas. These studies show, for the first time, a unique link between fibrin(ogen) and the development of inflammation-driven malignancy. Given the importance of antecedent inflammation in the progression of numerous cancers, these studies suggest that therapies targeting fibrin(ogen)-alpha(M)beta(2) interactions may be useful in preventing and/or treating this important subset of malignancies.
Requisite Role for Interleukin-4 in the Acceleration of Fatty Streaks Induced by Heat Shock Protein 65 or <i>Mycobacterium tuberculosis</i>
Authors: Jacob George, Yehuda Shoenfeld, Boris Gilburd, Arnon Afek, Aviv Shaish, Dror Harats
Journal: Circulation Research (2000)

Atherosclerotic lesions can be induced in rabbits and mice immunized with heat shock protein 65 (HSP65). In the current study, we investigated the role of interleukin (IL)-4 in the HSP65- and Mycobacterium tuberculosis (MT)-induced models that exhibit an inflammatory phenotype. Fatty streak formation in IL-4-knockout (IL-4 KO) mice immunized with HSP65 or MT was significantly reduced when compared with lesions in wild-type C57BL/6 mice. However, when injected with control (HSP-free) adjuvant, no differences were evident in the lesion size between wild-type and the IL-4 KO mice. Next, we studied comparatively the extent of humoral and cellular immune responses to HSP65 in the IL-4 KO and wild-type mice, as those are thought to be influential in murine atherosclerosis. Anti-HSP65 antibody levels were reduced in the HSP65-immunized IL-4 KO mice as compared with their wild-type littermates, whereas no differences were evident between the groups with respect to the primary cellular immune response to HSP65. Other than the absence of IL-4 in the knockout mice, the pattern of secreting cytokines interferon-gamma and IL-10 in concanavalin A-primed splenocytes was similar between the groups. HSP65-primed inguinal lymphocytes from IL-4 KO mice immunized with HSP65 secreted higher levels of interferon-gamma (previously shown to be proatherogenic in vivo) as compared with their wild-type controls. 12-/15-Lipoxygenase expression, known to be regulated by IL-4 and to contribute to murine atherosclerosis, in the lesions was not influenced by the immunization protocol used or by IL-4 disruption. Thus, IL-4 may prove a principal cytokine in the progression of early "inflammatory" atherosclerotic lesions and may serve as a target for immunomodulation.
Vascular rarefaction mediates whitening of brown fat in obesity
Authors: Ippei Shimizu, Tamar Aprahamian, Ryosuke Kikuchi, Ayako Shimizu, Kyriakos N. Papanicolaou, Susan MacLauchlan, Sonomi Maruyama, Kenneth Walsh
Journal: Journal of Clinical Investigation (2014)

Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished β-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism.
Functional and Organic
Authors: ALFRED P. FRENCH
Journal: Annals of Internal Medicine (1970)

Letters and Comments1 March 1970Functional and OrganicALFRED P. FRENCH, M.D.ALFRED P. FRENCH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-3-437_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Doctor Lipkin has made a significant contribution to medical education with his essay "Functional or Organic? A Pointless Question" which appeared in the November issue of the ANNALS.We are deeply immersed in the implications of the Cartesian mind-body dualism which has made a rigorously mechanistic approach to physiological phenomena possible on the one hand but has saddled us with the image of man as a "ghost in a machine" on the other. We have become biological mechanics. If we cannot tinker with the machine, we scorn and resent the mischievious ghost. How many patients have learned...References1. MENNINGER K: The Vital Balance. New York, The Viking Press, 1963 Google Scholar2. SPERRY R: Neurology and the mind-brain problem, in Basic Readings in Neuropsychology, edited by ISAACSON RL, New York, Harper and Row, Publishers, 1964 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ALFRED P. FRENCH, M.D.Affiliations: University of Iowa Hospitals Iowa City, Iowa PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPsychiatry for the general physician: An educational imperative 1 March 1970Volume 72, Issue 3Page: 437-437KeywordsMedical education ePublished: 1 December 2008 Issue Published: 1 March 1970 PDF downloadLoading ...
Effect of Leptin Replacement on Intrahepatic and Intramyocellular Lipid Content in Patients With Generalized Lipodystrophy
Authors: Vinaya Simha, Lidia S. Szczepaniak, Anthony J. Wagner, Alex M. DePaoli, Abhimanyu Garg
Journal: Diabetes Care (2003)

OBJECTIVE—To investigate whether leptin-induced improvements in glycemic control, hyperlipidemia, and insulin sensitivity in hypoleptinemic patients with generalized lipodystrophies are accompanied by reduction in intrahepatic and intramyocellular lipid (IMCL) accumulation. RESEARCH DESIGN AND METHODS—We examined the effects 8–10 months of subcutaneous leptin replacement therapy on insulin sensitivity, IMCL, and intrahepatic lipid content in two patients with acquired generalized lipodystrophy and one patient with congenital generalized lipodystrophy. All patients had extreme lack of body fat, low plasma leptin levels, and elevated serum triglycerides, but only two had diabetes. Insulin sensitivity was measured by a high-dose (0.2 IU/kg) insulin tolerance test, as well as by hyperinsulinemic-euglycemic glucose clamp studies in two patients. IMCL and intrahepatic lipid content were measured by 1H magnetic resonance spectroscopy. All measurements were obtained before and during 2–10 months of leptin therapy. RESULTS—Glycemic control and lipoprotein levels markedly improved with leptin therapy in the two diabetic patients, and a slight improvement in lipoprotein levels was seen in the nondiabetic patients. Insulin stimulated glucose uptake during 60–120 min of the euglycemic clamp studies, and the rate of glucose disappearance during the insulin tolerance test nearly doubled with leptin therapy. As compared with the baseline period, after 8–10 months of leptin therapy, the mean intrahepatic lipid content was reduced by ∼80% and the IMCL content was reduced by ∼42%. CONCLUSIONS—Reduction in IMCL and intrahepatic lipid content may partly explain leptin-induced improvement in insulin sensitivity in patients with generalized lipodystrophy.
Inflammatory Bowel Disease in a Family
Authors: MARTIN D. GELFAND
Journal: Annals of Internal Medicine (1970)

The mother and all three children of a family developed inflammatory disease of the bowel within a 5-year period. Shortly before ulcerative procititis occurred in the mother the family was living in a section of Germany where the water supply was poorly controlled hygienically. The two sons developed severe progressive granulomatous colitis, leading to total colectomy within 6 months of each other. Similar colon pathology characterized by deep longitudinal ulcerations was found. Disease occurred in the previously uninvolved small bowel of both children less than 1 year after surgery. The daughter's illness was manifested by aphthous stomatitis and arthritis. Diarrhea, weight loss, and fever then occurred with severe ileocolitis evident radiologically. Glucose-6-phosphate dehydrogenase values, immunoglobulin levels, and a chromosome analysis were unremarkable. Experience with this family supports the concept of a hereditary mechanism still unidentified in the cause of inflammatory bowel disease which may be precipitated by environmental stimuli.