tbuckley/cabot-search huggingface dataset:
Doctor and Son
Authors: C. Gregory Elliott
Journal: Annals of Internal Medicine (2012)

On Being a Doctor3 January 2012Doctor and SonC. Gregory Elliott, MDC. Gregory Elliott, MDFrom Intermountain Medical Center at the University of Utah, Murray, UT 84107.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-1-201201030-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Dad was weak and disoriented. His skin was mottled and cool. His blood pressure was dangerously low, and he was not making much urine. Were his doctors and nurses paying attention? Did they know if he was septic? Had they left the lines in too long? I was alarmed, but I stayed on the sideline, concerned and vigilant.Later that morning, Dad tried to sit forward, pulling against his restraints. He looked me in the eye and said, “Let's get out of here.” I knew that he meant it. I had visions of us tiptoeing down the hall, catheters trailing ... Author, Article, and Disclosure InformationAffiliations: From Intermountain Medical Center at the University of Utah, Murray, UT 84107.Corresponding Author: C. Gregory Elliott, MD, Intermountain Medical Center, 5121 South Cottonwood Street, Suite 307, Murray UT 84107; e-mail, greg.[email protected]org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 January 2012Volume 156, Issue 1_Part_1Page: 64-65KeywordsCathetersIntensive care unitsTracheostomyUrineVentilatorsVentricular tachycardiaVisionVital signsWeaningWine ePublished: 3 January 2012 Issue Published: 3 January 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Management of arteriovenous fistulas
Authors: Abul Siddiky, Kashif Sarwar, Niaz Ahmad, James Gilbert
Journal: BMJ (2014)

HMR1098, a novel K<sub>ATP</sub>-blocking agent, is metabolized to form an <i>S</i>-glucuronide in rat and dog bile. Synthesis of the <i>S</i>-glucuronide metabolite was studied in human liver and kidney microsomes. Recombinant UPD-glucuronosyltransferases (UGTs) were screened for activity, and kinetic analysis was performed to identify the isoform or isoforms responsible for the formation of this novel <i>S</i>-glucuronide in humans. <i>S</i>-Glucuronidation is relatively rare, but from this study it appears that <i>S</i>-glucuronides are not generated exclusively by a single UGT isoform. From the panel of recombinant isoforms used, both UGT1A1 and UGT1A9 catalyzed the glucuronidation of HMR1098. The <i>V</i><sub>max</sub> values in both instances were similar, but the <i>K</i><sub>m</sub> for UGT1A1 was substantially lower than that measured for UGT1A9, 82 μM compared with 233 μM, respectively. Liver and kidney microsomes displayed similar <i>K</i><sub>m</sub> values, but the <i>V</i><sub>max</sub> in kidney was more than 20-fold less than in liver microsomes, which is suggestive of a significant role for the bilirubin UGT in catalysis of HMR1098, although other UGTs may play a secondary role.
Glucokinase Gene Variants in Subjects With Late-Onset NIDDM and Impaired Glucose Tolerance
Authors: Markku Laakso, Mari Malkki, Päivi Kekäläinen, Johanna Kuusisto, Leena Mykkänen, Samir S Deeb
Journal: Diabetes Care (1995)

OBJECTIVE To investigate the frequency of variants of the glucokinase (GCK) gene in subjects with late-onset non-insulin-dependent diabetes mellitus (NIDDM) and in subjects with late-onset impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS The study population included 36 Finnish patients with late-onset NIDDM who were treated with diet for &amp;gt;8 years or who were newly diagnosed and 40 subjects with late-onset IGT who had low or normal insulin levels when tested by an oral glucose tolerance test. All exons, exon-intron junctions, and islet and liver promotor regions of the GCK gene were amplified with the polymerase chain reaction and screened for mutations using single-strand conformation polymorphism analysis. RESULTS A silent third-base substitution (TAC→TAT) in codon 215 of exon 6 was found in 2.8% of NIDDM patients and in 5.0% of IGT subjects. Polymorphisms were found in islet exon 1 at nucleotide 403 (C→G) in 16.7% of NIDDM patients and in 17.5% of IGT subjects and in the noncoding region of the islet promotor at nucleotide -30 (G→A) in 13.9% of NIDDM patients and in 25.0% of IGT subjects. Furthermore, in liver intron 1 a variant (C→T), 12 base pairs upstream from the splice acceptor site, was found in 5.6% of NIDDM patients and in 7.5% of IGT subjects. CONCLUSIONS These results indicate that the mutations in the coding region of the GCK gene are not likely to play a major role in the pathogenesis of late-onset NIDDM or IGT in the Finnish population.
SHORT–TERM EXERCISE TRAINING CHANGES TRIGLYCERIDES MOLECULAR CONTENT OF THE LDL AND HDL PARTICLES AFFECTING THEIR FUNCTIONAL CHARACTERISTICS IN METABOLIC SYNDROME
Authors: Antonio Casella–Filho, Ivani Trombetta, Paulo Magno Dourado, Antonio Carlos Leite–Junior, Marilia CO Sprandel, Alexandre Segre, Raul Santos, Carlos Eduardo Negrao, Raul C Maranhao, Antonio Chagas
Journal: Journal of the American College of Cardiology (2013)
Micrornas: Emerging key regulators of hematopoiesis
Authors: Violaine Havelange, Ramiro Garzon
Journal: American Journal of Hematology (2010)

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by pairing with their target mRNAs, thereby inducing protein translation inhibition or/and mRNA degradation. There is now strong evidence that miRNAs play a crucial role in the regulation of hematopoiesis. Several groups have shown that miRNA expression change dynamically during hematopoietic differentiation and functional studies demonstrated that miRNAs control not only differentiation but also activity of hematopoietic cells by targeting transcription factors, growth factor receptors, and specific transcripts involved in the modulation of cellular responses to external stimuli. In this review, we will summarize the current knowledge of miRNA expression and function during hematopoiesis and discuss controversies and future directions.
TCTAP A-023 Impact of Different Subtypes of Microvascular Dysfunction on Myocardial Strains in ST-segment Elevation Myocardial Infarction Patients Treated with Reperfusion Therapy
Authors: Heng Ge, Hang Zhao, Zheng Li, Weiming Chai, Xin Ge, Zizhou Zhao, Li Zhu, Jun Pu, Jianrong Xu, Xuedong Shen
Journal: Journal of the American College of Cardiology (2014)
Real-Time Magnetic Resonance Imaging–Guided Focal Laser Therapy in Patients with Low-Risk Prostate Cancer
Authors: Orit Raz, Masoom A. Haider, Sean R.H. Davidson, Uri Lindner, Eugen Hlasny, Robert Weersink, Mark R. Gertner, Walter Kucharcyzk, Stuart A. McCluskey, John Trachtenberg
Journal: European Urology (2010)
The Impact of Medicare on Psychiatry
Authors: WENDELL R. LIPSCOMB
Journal: American Journal of Psychiatry (1968)

Medicare is having a tremendous impact on psychiatry and the rest of medicine. The author feels that the restrictions on psychiatric coverage in this law, rather than being a handicap, should serve as a challenge to the profession to modify existing practices and attitudes so that psychiatry can meaningfully cope with the benevolent philosophy of the legislation.
Breast conserving treatment for ductal carcinoma in situ in the elderly: Can radiation therapy be avoided? Our experience
Authors: Giuseppe Falco, Nicola Rocco, Eugenio Procaccini, Maria Giulia Sommella, Daniele Bordoni, Eugenio Cenini, Fabio Castagnetti, Vincenzo Sabatino, Rita Compagna, Gianni Antonio Della Corte, Antonello Accurso, Bruno Amato, Guglielmo Ferrari
Journal: International Journal of Surgery (2014)
Antibiotic-Associated Colitis: Always Pseudomembranous?
Authors: G. Di Febo, G. Milazzo, G. Gizzi, G. Biasco, M. Miglioli
Journal: Endoscopy (1982)

Among the 14 cases of antibiotic-induced colitis, endoscopic features were: in 9 cases typical pseudomembranes, in 4 cases petechiae or ecchymosis or suggillation-like redness with near-to-normal surrounding mucosa. In one case induced by Spiramycin, a macrolide that had never been previously indicated as being responsible for the disease, the endoscopic picture was 'atypical' and directed us towards a severe ulcerative colitis. These forms are very rare and usually limited to the right or transverse colon which suggests, if possible, a total colonoscopy. The nosographic picture of these cases is not quite clear, since they could represent both the most severe stages within 'non-pseudomembranous' antibiotic-induced colitis and autonomous forms whose evolution does not contribute in any way to the formation of pseudomembranes.
Metastatic Female Adnexal Tumor of Possible Wolffian Origin (FATWO) of the Appendix Demonstrated by FDG PET/CT
Authors: Yiyan Liu
Journal: Clinical Nuclear Medicine (2011)

Both female adnexal tumor of possible wolffian origin (FATWO) and metastasis to the appendix from any primary tumor are extremely rare entities. The appendiceal metastasis from FATWO has not been reported, and there is a lack of the literature regarding FDG PET/CT study in both. We reported the case of an appendiceal metastasis from FATWO, demonstrated by F-18 FDG PET/CT. The case highlights the significance of FDG uptake in the appendix. When interpreting FDG PET/CT, caution should be exercised to identify uptake in the appendix, because it is easily misinterpreted as bowel activity.
Private practice and the reduction of pay-beds.
Authors: D E Bolt
Journal: BMJ (1978)

Post-approval changes are inevitable and necessary throughout the life of a drug product—to implement new knowledge, maintain a state of control, and drive continual improvement. Many post-approval changes require regulatory agency approval by individual countries before implementation. Because of the global regulatory complexity, individual post-approval changes usually take years for full worldwide approval even when they reduce patient risk, improve compliance, or enhance the manufacturing process or test methods. This global complexity slows down continual improvement and innovation and can cause drug shortages and current good manufacturing practices compliance issues. Manufacturers that market products globally experience the greatest challenge and risks in their daily operations because of this post-approval change complexity. A global problem needs a global solution. This paper has been sponsored and endorsed by senior quality leaders (Chief Quality Officers/Heads of Quality) from &gt;20 global pharmaceutical companies who have collaborated to speak with “One-Voice-Of-Quality” (1VQ). The paper provides two specific solutions that lay the foundation for an aligned and standardized industry position on the topic of effective management of post-approval changes in the pharmaceutical quality system (PQS). This document represents the 1VQ standard approach for the steps necessary to establish and demonstrate an effective quality system to fully leverage a risk-based approach to post-approval changes as laid out by ICH Q10 Annex 1. Implementation of the solutions presented in this paper can help achieve a transformational shift with faster implementation of new knowledge, continual improvement, and innovation through post-approval changes. The Chief Quality Officers/Heads of Quality are inviting other companies to join the 1VQ (contact either Emma Ramnarine or Anders Vinther) and other stakeholders to join the dialog.
Interleukin-15 enhances cellular proliferation and upregulates CNS homing molecules in pre-B acute lymphoblastic leukemia
Authors: Mark T. S. Williams, Yasar Yousafzai, Charlotte Cox, Allison Blair, Ruaidhrí Carmody, Shuji Sai, Karen E. Chapman, Rachel McAndrew, Angela Thomas, Alison Spence, Brenda Gibson, Gerard J. Graham, Christina Halsey
Journal: Blood (2014)
Abstract 3049: Pathways of transformation in Kit-activated melanoma
Authors: Ruixia Liang
Journal: Cancer Research (2011)

Abstract KIT-activated melanoma is a recently recognized distinct genetic form of melanoma characterized by constitutively activating KIT mutations. To understand the biology of KIT-activated melanoma, we sought to develop both in vitro and in vivo models. Mouse Kit L575P, the orthologue of human KIT L576P, a common KIT mutation found in human melanoma, was expressed in an immortalized but non-transformed mouse Ink4a/Arf-deficient melanocyte cell line. The resultant Kit L575P cell line exhibited increased proliferation, the ability to grow in soft agar and increased migration, indicating that the cells had been transformed by Kit L575P. Furthermore, when Kit L575P cells were injected subcutaneously into NOD/SCID/gamma(c) mice, tumors with all of the histological and clinical hallmarks of melanomas arose in 5 of 7 (71%) mice, while control cells harboring wild-type Kit failed to develop tumors. In addition to a subcutaneous tumor, 1 of 7 mice (14%) injected with Kit L575P cells developed metastatic disease to liver and lungs. Evaluation of signal transduction pathways downstream of constitutively activated Kit L575P revealed striking activation of the phosphatidyl inositol 3-kinase (PI3K) pathway. Inhibition of the PI3K pathway pharmacologically with the PI3K inhibitor LY294002 or genetically by engineering a second Kit mutation (Y719F) which abrogated binding of Kit L575P to the p85α subunit of PI3K, abolished the transformation phenotypes gained in the L575P single mutant. These studies validate this Kit L575P-activated model of melanoma and establish the PI3K pathway as a dominant signaling pathway downstream of Kit in melanoma. This model should be of further use in the pre-clinical evaluation of various therapeutic strategies in Kit-activated melanoma and for studying different aspects of the biology of Kit-activated melanoma. 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 3049. doi:10.1158/1538-7445.AM2011-3049
Caspase-Dependent Apoptosis Induction by Phenethyl Isothiocyanate, a Cruciferous Vegetable-Derived Cancer Chemopreventive Agent, Is Mediated by Bak and Bax
Authors: Dong Xiao, Yan Zeng, Sunga Choi, Karen L. Lew, Joel B. Nelson, Shivendra V. Singh
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The present study was undertaken to gain insights into the molecular mechanism of apoptosis induction by phenethyl isothiocyanate (PEITC) using prostate cancer cell lines derived from transgenic adenocarcinoma mouse prostate (TRAMP) mice (TRAMP-C1 and TRAMP-C2). Experimental Design and Results: The viability of TRAMP-C1 and TRAMP-C2 cells was reduced significantly in the presence of PEITC in a concentration-dependent manner as determined by sulforhodamine B and trypan blue dye exclusion assays. Treatment of TRAMP-derived cells with PEITC revealed features characteristic of apoptosis induction, including appearance of subdiploid cells (determined by flow cytometry), cytoplasmic histone-associated DNA fragmentation (determined by an ELISA assay), and cleavage of caspase-3 (determined by immunoblotting). The PEITC-induced apoptosis in TRAMP-derived cells was associated with a marked increase in the level of proapoptotic protein Bak and/or a decrease in the levels of antiapoptotic protein Mcl-1 or Bcl-xL and disruption of mitochondrial membrane potential. The SV40 immortalized mouse embryonic fibroblasts derived from Bak and Bax double knockout mice were significantly more resistant to PEITC-induced DNA fragmentation compared with wild-type or Bak−/− mouse embryonic fibroblasts. The PEITC-induced apoptosis in both cell lines was significantly attenuated in the presence of caspase inhibitors zVAD-fmk, zLEHD-fmk, and zIETD-fmk. Oral administration of PEITC (9 or 12 μmol PEITC/d, Monday-Friday) significantly retarded growth of TRAMP-C1 xenografts in nude mice without causing weight loss or any other side effects. Conclusion: The results of the present study indicate that caspase-dependent apoptosis by PEITC is mediated by Bak and Bax proteins.
The Patient: Biological, Psychological, and Social Dimensions of Medical Practice
Authors: Sara C. Charles
Journal: JAMA (1986)

Critics of medical education frequently chastise the profession for its failure in undergraduate training programs to emphasize the importance of the relationship and understanding between doctor and patient. In recent years, the response to this concern has been the introduction of behavioral science courses early in the curriculum, which integrate basic science principles of human behavior with a clinical perspective. These courses provide a humanistic foundation for students as they begin their transformation into practicing clinicians. <i>The Patient</i>, by psychiatry professors Hoyle Leigh and Morton F. Reiser, is an outgrowth of their efforts at Yale to develop such a course and an update of their successful first edition. This book is, in the authors' words, "intended to challenge medical students in their preclinical years and those who are preparing for their first clinical clerkship... to think about patients as entities in their own right." It is<i>not</i>, however, a "conventional
Diagnosing Suffering: A Perspective
Authors: Eric J. Cassell
Journal: Annals of Internal Medicine (1999)

The alleviation of suffering is crucial in all of medicine, especially in the care of the dying. Suffering cannot be treated unless it is recognized and diagnosed. Suffering involves some symptom or process that threatens the patient because of fear, the meaning of the symptom, and concerns about the future. The meanings and the fear are personal and individual, so that even if two patients have the same symptoms, their suffering would be different. The complex techniques and methods that physicians usually use to make a diagnosis, however, are aimed at the body rather than the person. The diagnosis of suffering is therefore often missed, even in severe illness and even when it stares physicians in the face. A high index of suspicion must be maintained in the presence of serious disease, and patients must be directly questioned. Concerns over the discomfort of listening to patients' severe distress are usually more than offset by the gratification that follows the intervention. Often, questioning and attentive listening, which take little time, are in themselves ameliorative. The information on which the assessment of suffering is based is subjective; this may pose difficulties for physicians, who tend to value objective findings more highly and see a conflict between the two kinds of information. Recent advances in understanding how physicians increase the utility of information and make inferences allow one to reliably use the subjective information on which the diagnosis and treatment of suffering depend. Knowing patients as individual persons well enough to understand the origin of their suffering and ultimately its best treatment requires methods of empathic attentiveness and nondiscursive thinking that can be learned and taught. The relief of suffering depends on physicians acquiring these skills.
Age-related appearance of outward currents may contribute to developmental differences in ventricular repolarization.
Authors: C D Jeck, P A Boyden
Journal: Circulation Research (1992)

Ventricular repolarization significantly influences contractility, refractoriness, and ion channel state. Factors affecting repolarization will thus affect these secondary phenomena. To understand the influence of age on ventricular repolarization, we studied neonatal, young, and adult dogs using electrocardiogram, action potential, and whole-cell voltage-clamp recordings from single epicardial myocytes. Hearts of neonatal and 57-58-day-old dogs require a significantly longer time for repolarization than those of adult dogs, as determined by analysis of rate-corrected QT and JT (QT minus QRS) intervals. Epicardial action potentials of neonates are significantly longer than those of adults, as determined by measurements of duration at 50% and 90% repolarization. The adult action potential is characterized by a large phase 1 notch that is absent from neonatal recordings. This notch develops between 58 and 64 days of age, and by 64-68 days of age, it is equal to that in adults. In addition, action potentials recorded from adult and young epicardial muscle are more greatly affected by rapid pacing and superfusion of 2 mM 4-aminopyridine than are potentials recorded from neonatal tissue. Whole-cell voltage-clamp recordings reveal a 4-aminopyridine-sensitive transient outward current in adult myocytes that is absent from neonatal myocytes. The correlation between developmental changes in the 4-aminopyridine-sensitive current, the action potential, and the QT interval suggests that the transient outward current may be an important determinant in the relation between age and repolarization.
Prolonged Remissions of Cystic and Conglobate Acne with 13-cis-Retinoic Acid
Authors: Gary L. Peck, Thomas G. Olsen, Frank W. Yoder, John S. Strauss, Donald T. Downing, Mangala Pandya, Danute Butkus, Jeanne Arnaud-Battandier
Journal: New England Journal of Medicine (1979)

Fourteen patients with treatment-resistant cystic and conglobate acne were treated for four months with oral 13-cis-retinoic acid, a synthetic isomer of naturally occurring all-trans-retinoic acid. The average dose was 2.0 mg per kilogram per day. Thirteen patients experienced complete clearing of their disease; the other had 75 per cent improvement, as determined by the number of acne nodules and cysts present before and after therapy. Prolonged remissions, currently lasting as long as 20 months after discontinuation of therapy, have been observed in all 14 patients. Clinical toxicity was limited to the skin and mucous membranes in most patients and was dose dependent and rapidly reversible upon discontinuation of therapy. The mechanism of action of 13-cis-retinoic acid in the therapy of acne probably involves a direct inhibitory effect of the drug on the sebaceous gland. (N Engl J Med 300:329–333, 1979)