tbuckley/cabot-search huggingface dataset:
Elastin metabolism and chemistry: potential roles in lung development and structure.
Authors: R B Rucker, M A Dubick
Journal: Environmental Health Perspectives (1984)

Elastic fibers are important for elasticity and extensibility of lung tissue. In the developing lung, elastic fibers appear in greatest numbers during the process or period of alveolarization . A variety of mesenchymal cells in lung appear responsible for elastin synthesis. Elastin is a novel protein both from the standpoint of its processing into elastic fibers and chemical properties. For example, elastin undergoes posttranslational modification before its assembly into fibers. These steps include limited proteolysis, hydroxylation of prolyl residues and the oxidative deamination of lysyl residues prior to their incorporation into the crosslinks that covalently bond together polypeptide chains of elastin. The crosslinking amino acids include lysinonorleucine , merodesmosine and desmosine isomers. A key enzyme that controls this process is lysyl oxidase. Lysyl oxidase is a copper metalloprotein whose activity is responsive to and modulated by environmental insults, nutrition deficiencies and the administration of various pharmacological agents. Regarding chemical properties, elastin is one of the most apolar proteins secreted by mammalian cells. Moreover, elastin is one of the most long-lived proteins secreted into the extracellular matrix. In relationship to its processing into elastic fibers and chemical properties, details related to major aspects of elastin metabolism as well as speculation on its potential as a factor in lung development and disease are discussed.
Linkage of the gene for cystinosis to markers on the short arm of chromosome 17
Authors: Geraldine A. McDowell, William A. Gahl, Leah A. Stephenson, Jerry A. Schneider, Jean Weissenbach, Mihael H. Polymeropoulos, Margaret M. Town, William van't Hoff, Martin Farrall, Christopher G. Mathew
Journal: Nature Genetics (1995)
T-WAVE ALTERNANS (TWA) IS ASSOCIATED WITH CARDIOVASCULAR MORTALITY AND NSVT IN THE MERLIN-TIMI 36 TRIAL OF RANOLAZINE VERSUS PLACEBO IN PATIENTS WITH NON-ST SEGMENT elevation ACUTE CORONARY SYNDROME
Authors: Benjamin Scirica, Tuomo Nieminen, Jose RM Pegler, Caio Tavares, Vitor PF Pagotto, Alexandre F. Kanas, Marcel F. Sobrado, Bruce Nearing, Ji Cho, David Morrow, Luiz Belardinelli, Richard Verrier
Journal: Journal of the American College of Cardiology (2013)
Uterine Perforation by Contraceptive Devices
Authors: W. Mills
Journal: BMJ (1967)

MEDICBALJOURNAL 427 of four adult patients with the nephrotic syn- drome that there was a great increase in inhibitory effect on fibrinolysis by their plasma compared with age-and sex-matched controls.In each of these patients serum alpha-2 globulin was increased.I would also draw attention to the fact that though corticosteroids produce hyper- coagulability of the blood' they also markedly increase blood fibrinolytic activity,' but which of these actions predominates in any given circumstance is not known.-Iam, etc.,
Contamination of Poliovirus Vaccines With Simian Virus 40 (1955-1963) and Subsequent Cancer Rates
Authors: Howard D. Strickler
Journal: JAMA (1998)

Poliovirus vaccine contaminated with live simian virus 40 (SV40), a macaque polyomavirus that is tumorigenic in rodents, was used extensively in the United States between 1955 and 1963. Simian virus 40 DNA has recently been detected in several rare human tumors, including ependymomas, osteosarcomas, and mesotheliomas.To determine the risk of ependymoma, osteosarcoma, and mesothelioma among Americans who as children received SV40-contaminated poliovirus vaccine.Retrospective cohort study using data from the Surveillance, Epidemiology, and End Results program (1973-1993) and the Connecticut Tumor Registry (1950-1969), as well as national mortality statistics (1947-1973).United States.Birth cohorts that were likely to have received SV40-contaminated poliovirus vaccine as infants, born 1956 through 1962 (60 811730 person-years of observation); as children, born 1947 through 1952 (46430953 person-years); or that were unexposed, born 1964 through 1969 (44959979 person-years).Relative risk (RR) of each cancer among exposed compared with unexposed birth cohorts.Age-specific cancer rates were generally low and were not significantly elevated in birth cohorts exposed to SV40-contaminated vaccine. Specifically, compared with the unexposed, the relative risk of ependymoma was not increased in the cohorts exposed as infants (RR, 1.06; 95% confidence interval [CI], 0.69-1.63), or as children (RR, 0.98; 95% CI, 0.57-1.69) nor did the exposed have an increased risk of all brain cancers. Osteosarcoma incidence also showed no relation to exposure as infants (RR, 0.87; 95% CI, 0.71-1.06) or children (RR, 0.85; 95% CI, 0.59-1.22). Last, mesotheliomas were not significantly associated with exposure, although the cohorts studied have not yet reached the age at which these tumors tend to occur.After more than 30 years of follow-up, exposure to SV40-contaminated poliovirus vaccine was not associated with significantly increased rates of ependymomas and other brain cancers, osteosarcomas, or mesotheliomas in the United States.
UK public health plan aims to save 300 000 lives in next decade
Authors: S. Mayor
Journal: BMJ (1999)

The UK government this week published its strategy for public health in a white paper aimed at improving the health of the whole nation, but particularly that of the financially worst off over the next decade. Several measures were introduced to reduce inequalities in health but there was more emphasis on improving individual responsibility for health than has traditionally been expected from the Labour party.

The secretary of state for health, Frank Dobson, said the aim of the public health strategy was to reduce the total number of deaths from heart disease, cancer, accidents, and suicide by 300000 …
Further experience with indomethacin in the treatment of rheumatic disorders.
Authors: M. Thompson, J. S. Percy
Journal: BMJ (1966)

Indomethacin (Indocid) is an indole-3-acetic acid derivative, which was found to have powerful anti-inflammatory and anal gesic properties, and which has been under clinical investiga tion since October 1962. Several controlled trials demonstrated that it had some value in the treatment of rheumatic disorders, being significantly more effective than placebos in the treatment of both rheumatoid arthritis (Wanka, Jones, Wood, and Dixon, 1964) and osteoarthrosis of the hip (Wanka and Dixon, 1964). When indomethacin was compared with phenylbutazone in a controlled trial in rheumatoid arthritis (Percy, Stephenson, and Thompson, 1964) no significant difference was noted either in terms of relief of pain or by improvement in grip-strength, but side-effects were commoner with indomethacin. All these early studies were undertaken with indomethacin in tablet form, and it was found that this preparation had disadvantages owing to variable dissolution rates of the tablets and erratic absorption from the gastro-intestinal tract. The use of capsules, available since September 1963, overcame these difficulties, and sub sequent clinical experience indicated that a commensurate clinical effect could be obtained with a lower dosage of indo methacin in capsule form than when it was administered as tablets (Thompson, 1964). Experience with other drugs used in the treatment of chronic rheumatic disorders, notably with the predni-steroids, has shown that potency of a drug does not establish its place as the therapeutic agent of choice. Controlled clinical trials of short duration serve to estimate the immediate value of a drug and any early side-effects, but it is only by means of long-continued clinical experience that answers may be provided to such ques tions as the frequency, severity, and nature of adverse side effects, optimum dosage levels, and the indications for or against the use of the drug. As indomethacin became available for use in general practice in March 1965 we are recording our experience of a group of 137 patients treated with 25-mg. capsules during the 82 weeks from September 1963 to April 1965.
The laws of thermodynamics
Authors: K. Barraclough
Journal: BMJ (1999)

I was sitting on the end of the old man's bed listening to stories of his life. I was a medical student at the time. The odd thing, he had said, was that the world made no more sense to him then than it had when he was a boy. He had thought that things would become clearer with age. I remember the perplexity in his watery eyes. Somehow, time had crept up on him before …
Survival after liver transplantation: Is racial disparity inevitable?
Authors: Tae Hoon Lee, Nilay Shah, Rachel A. Pedersen, Walter K. Kremers, Charles B. Rosen, Goran B. Klintmalm, Ray W. Kim
Journal: Hepatology (2007)

Previous analyses have reported that minority patients undergoing orthotopic liver transplantation (OLT) have poorer survival than Caucasian recipients. The reason for this disparity is unclear. We examined whether racial differences in survival exist at select academic OLT centers. OLT recipients from 4 academic centers were prospectively enrolled in 2 multicenter databases. Data including demographics, liver disease diagnosis, and post-OLT follow-up were obtained for 2823 (135 African, 2448 Caucasian, and 240 other race) adult patients undergoing primary OLT between 1985 and 2000. The survival of patients and grafts after OLT was compared across race. The Kaplan-Meier estimates for 1-year recipient survival were 90.8% [95% confidence interval (CI): 86.0–95.9] for African Americans, 86.5% (95% CI: 85.1–87.9) for Caucasians, and 84.4% (95% CI: 79.8–89.2) for other races. The 5-year recipient survival probability was 69.2% (95% CI: 60.1–79.7) for African Americans, 72.2% (95% CI: 70.1–74.4) for Caucasians, and 67.5% (95% CI: 60.5–75.3) for other races. The 10-year recipient survival probability for African Americans was 54.4% (95% CI: 41.1–72.1), for Caucasians 50.7% (95% CI: 46.4–55.3), and for other races 55.7% (95% CI: 41.5–74.8). There was no difference in patient survival ( P = 0.162) or graft survival ( P = 0.582) among racial groups. A multivariable proportional hazards model confirmed the absence of an association between race and post-OLT survival after adjustments for age, gender, total bilirubin, creatinine, prothrombin time, and diagnosis. Conclusion: These data demonstrate that as a proof of principle, minority OLT recipients should not necessarily expect an OLT outcome inferior to that of Caucasians.
Effect of loteprednol etabonate nasal spray suspension on seasonal allergic rhinitis assessed by allergen challenge in an environmental exposure unit
Authors: N. Krug, J. M. Hohlfeld, H. Geldmacher, M. Larbig, R. Heermann, N. LaVallee, D. T. Nguyen, U. Petzold, R. Hermann
Journal: Allergy (2005)

Background: Loteprednol etabonate (LE) is a novel soft steroid that was designed to improve the benefit/risk ratio of topical corticosteroid therapy. This study assesses the clinical efficacy and safety of three different doses of LE nasal spray in seasonal allergic rhinitis (SAR). Methods: In this single‐center, double‐blind, placebo‐controlled, parallel‐group trial 165 subjects with SAR to grass pollen received daily single doses of either 100, 200, 400 μ g LE nasal spray, or placebo for 14 days. The patients underwent three 4‐h allergen challenges with grass pollen in an environmental exposure unit at a screening visit (baseline) and on days 7 and 14 of treatment. Standardized nasal symptom scores were obtained every 20 min. Nasal flow, nasal secretions, and FEV 1 were measured every hour during allergen challenges. Results: After 14 days of treatment, patients who received 400 μ g LE had significantly lower total nasal symptom scores compared with those receiving placebo ( P = 0.007). LE400 reduced rhinorrhea, nasal congestion, nasal itching, the amount of nasal secretions, and improved nasal flow as compared with placebo ( P &lt; 0.05). LE100 and LE200 were not significantly different from placebo. All treatments were well tolerated. Conclusions: Loteprednol 400 μ g once daily is superior to placebo and the only effective dose tested in improving nasal symptoms and objective parameters in patients with SAR.
Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols
Authors: S Z Usmani, B Nair, P Qu, E Hansen, Q Zhang, N Petty, S Waheed, J D Shaughnessy, Y Alsayed, C J Heuck, F van Rhee, T Milner, A Hoering, J Szymonifka, R Sexton, J Sawyer, Z Singh, J Crowley, B Barlogie
Journal: Leukemia (2012)
Distinct Criteria for Termination of Resuscitation in the Out-of-Hospital Setting
Authors: Marni J. Bonnin
Journal: JAMA (1993)

To identify distinct criteria for appropriate on-scene termination of resuscitation efforts for out-of-hospital cardiac arrest when on-scene interventions fail to restore spontaneous circulation.For 18 months, all out-of-hospital cardiac arrests were evaluated prospectively for survival to hospital discharge and for all established survival predictors including age, gender, presenting cardiac rhythm, whether it was a witnessed event, performance of basic cardiopulmonary resuscitation by bystanders, and interval to paramedic arrival and return of spontaneous circulation (ROSC).A large municipality with a single, centralized emergency medical services program.All normothermic adults treated for out-of-hospital, unmonitored, primary cardiac arrest.Standard advanced cardiac life support provided at the scene by paramedics.The number and circumstances of patients achieving survival to hospital discharge following failure to achieve on-scene ROSC.Of 1461 consecutive primary cardiac arrests, 139 were monitored (paramedic witnessed), including 59 that occurred en route to the hospital. Of the 1322 unmonitored patients, 370 achieved ROSC at the scene. Only six (0.6%) of the 952 who did not achieve ROSC at the scene survived, and all six were readily identifiable as having persistent ventricular fibrillation. Excluding those patients with persistent ventricular fibrillation, all survivors achieved ROSC within 25 minutes after paramedic arrival.Excluding patients with persistent ventricular fibrillation, resuscitative efforts can be terminated at the scene when normothermic adults with unmonitored, out-of-hospital, primary cardiac arrest do not regain spontaneous circulation within 25 minutes following standard advanced cardiac life support. These criteria should now be validated in several large centers with high survival rates.
Effects of introducing ultra-low dose wartarin and aspirin on fibrin D-dimer and beta-thromboglobulin as markers of intravascular thrombogenesis and platelet activation in chronic atrial fibrillation
Authors: Gregory Y.H. Lip, Peck Lin Lip, John Zariffs, David Bareford, Gordon Lowe, Robert Watson, Gareth Beevers
Journal: Journal of the American College of Cardiology (1996)
The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus
Authors: Robert Flisiak, Andrzej Horban, Philippe Gallay, Michael Bobardt, Suganya Selvarajah, Alicja Wiercinska-Drapalo, Ewa Siwak, Iwona Cielniak, Jozef Higersberger, Jarek Kierkus, Christian Aeschlimann, Pierre Grosgurin, Valérie Nicolas-Métral, Jean-Maurice Dumont, Hervé Porchet, Raf Crabbé, Pietro Scalfaro
Journal: Hepatology (2008)

Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025-treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P < 0.01).Debio-025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.
Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias
Authors: Franck Emmanuel Nicolini, Grzegorz W. Basak, Simona Soverini, Giovanni Martinelli, Michael J. Mauro, Martin C. Müller, Andreas Hochhaus, Charles Chuah, Inge H. Dufva, Giovanna Rege-Cambrin, Giuseppe Saglio, Mauricette Michallet, Hélène Labussière, Stéphane Morisset, Sandrine Hayette, Gabriel Etienne, Eduardo Olavarria, Wei Zhou, Senaka Peter, Jane F. Apperley, Jorge Cortes
Journal: Blood (2011)
Diminished lymphocyte and granulocyte γ‐glutamyltranspeptidase activity in acute lymphocytic leukemia and response to chemotherapy
Authors: Sandra A. Russo, Michael B. Harris, Olga Greengard
Journal: American Journal of Hematology (1987)

gamma-Glutamyltranspeptidase (GGT) activity (per mg protein) in blood lymphoid cells of 27 children with acute lymphoblastic leukemia (ALL) (1.05 +/- 0.15) was significantly below that of controls (2.25 +/- 0.30), became normalized during chemotherapy-induced remission (2.47 +/- 0.26), and was low again (1.59 +/- 0.62) in relapsed subjects. Individual variations in the GGT activity of the blood lymphoid cell fraction (per mg protein) bore a significant inverse correlation to the number of white blood cells (WBC) as well as of blasts per ml blood. Blasts had minimal GGT activity; however, partial GGT deficiency was also exhibited by the microscopically normal circulatory lymphocytes of several patients prior to treatment and in relapsed subjects whose blood was still devoid of blasts. Significantly diminished GGT activity (per mg protein) was found in the blood granulocytes of ALL subjects. This deficit, restored during remission and present again at relapse, varied in magnitude but showed no statistically significant correlation to the different patients' degree of neutropenia. In about one-third of the newly diagnosed or relapsed pre-B ALL children, the circulatory granulocytes' GGT activity was only 10-20% of normal. The results suggest that 1) the presence or absence of this sign of functional maldifferentiation in granulocytes is a factor in the heterogeneity of disease manifestation among subjects with apparently the same type of ALL and that 2) measurement of GGT in the circulatory granulocytes, as well lymphocytes, may be useful for monitoring the efficacy of chemotherapy.
The transforming growth factor ?1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress
Authors: Afonso Ribeiro, Steven F. Bronk, Patricia J. Roberts, Raul Urrutia, Gregory J. Gores
Journal: Hepatology (1999)

Transforming growth factor β 1 (TGF-β 1 )-inducible transcription factors have recently elicited interest because of their critical role in the regulation of cell proliferation, differentiation, and apoptosis. We have previously reported that the TGF-β 1 -inducible transcription factor, TIEG1, induces apoptosis in a pancreas-derived cell line. However, the mechanisms underlying the apoptotic effects of this transcription factor remain to be defined. In this study, using the TGF-β 1 -sensitive Hep 3B cell line, we have defined the mechanistic sequence of events that characterize TIEG1-mediated apoptosis and compared these events with the changes observed during TGF-β 1 -induced apoptosis. Both TGF-β 1 - and TIEG1-induced cell death were accompanied by an increase in the generation of reactive oxygen species and a loss of the mitochondrial membrane potential preceding the morphological changes of apoptosis. In contrast, increases in caspase 3-like activity and glutathione (GSH) depletion occurred later in the apoptotic process, concurrent with the morphological features of apoptosis. The antioxidant, trolox, decreased the formation of reactive oxygen species and apoptosis. These results demonstrate that similar to TGF-β 1 , TIEG1 induces apoptosis by a mechanism involving the formation of reactive oxygen species.
Localization of Acute Inflammatory Foci in Man with 99m Tc-S.C. Labeled Granulocytes
Authors: BRIAN C. LENTLE, T ALEXANDER McPHERSON, JOHN R. SCOTT, FRANK I. JACKSON
Journal: Clinical Nuclear Medicine (1976)

Human granulocytes can be radiolabeled with 99mTc- S.C. and used to image sites of focal inflammation. Labeling is best achieved by culture, in the presence of serum, for one hour at 25°C. The cells remain viable and 80-85% of the injected activity is associated with the granulocyte fraction of blood. Of 52 patients investigated by the technique, 20 had sites of focal inflammation correctly identified and 19 had normal findings, with no focal disease subsequently identified. A falsenegative result occurred in 11 patients, with falsepositive findings in two. While of clinical help in localizing focal inflammation when positive, the examination does not reliably exclude this possibility at its present stage of evolution in our hands.
Physician Disclosure of Financial Incentives
Authors: Christine K. Cassel
Journal: Annals of Internal Medicine (1993)

Letters1 July 1993Physician Disclosure of Financial IncentivesChristine K. Cassel, MDChristine K. Cassel, MDChair, ACP Ethics CommitteeSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-1-199307010-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Yardney for his thoughtful letter about the third edition of the American College of Physicians Ethics Manual. Although the Manual does not include a detailed section specifically on ethical issues in managed care, we do note in the section Conflicts of Interest that there are many potential influences on clinical judgment, including financial incentives inherent in the practice environment (such as incentives to overutilize in the fee-for-service setting or underutilize in the managed care setting), and require physicians to be conscious of all potential influences. (with) their actions. guided by appropriate utilization and not by ...References1. American College of Physicians Ethics Committee. American College of Physicians Ethics Manual. Third edition. Ann Intern Med. 1992; 117:947-60. Google Scholar2. American College of Physicians Ethics Committee. Ethics case study: when finances may influence physician decision-making. ACP Observer. 1990; 10:1,8,9,12. Google Scholar Author, Article, and Disclosure InformationAffiliations: Chair, ACP Ethics Committee PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1993Volume 119, Issue 1Page: 95KeywordsConflicts of interestDisclosureMotivation Issue Published: 1 July 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...