tbuckley/cabot-search huggingface dataset:
Effect of interferon alfa on the dynamics of hepatitis C virus turnoverin vivo
Authors: S Zeuzem, J M Schmidt, J Lee, B Ruster, W K Roth
Journal: Hepatology (1996)

In about 30% to 40% of patients with chronic hepatitis C, treatment with recombinant interferon alfa (r-IFNα) causes a decrease of serum aminotransferases and hepatitis C virus (HCV) RNA. The antiviral mechanism of interferon alfa (IFNα) in vivo is unknown. From serial measurements of serum HCV-RNA concentrations following IFNα induced perturbation of the balance between virus production and clearance, we obtained kinetic information on the pretreatment steady-state of HCV. In patients with chronic hepatitis C responding to IFNα, HCV-RNA declined exponentially with a half life of approximately 2 days. Modeling of the data predicts that in patients with chronic hepatitis C responding to IFNα this cytokine predominantly acts as an inhibitor of de novo infection of susceptible cells. HCV is released from infected cells with a mean half life of 2.7 ± 1.3 days, whereas the clearance rate from serum is faster (mean half life, 0.7 ± 0.4 days). The minimum virus production and clearance per day in patients with chronic hepatitis C was calculated to be 6.7 × 10 10 virions/d (range, 0.2 to 43.8 × 10 10 virions/d). These values showed no correlation with the HCV genotype, aminotransferase levels, or the histological activity as assessed before the administration of r-IFNα. Simultaneous kinetic analysis of serum aminotransferases as surrogate markers of hepatocyte integrity revealed half lifes for the release of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from hepatocytes of 4.7 ± 3.8 and 3.0 ± 3.5 days, respectively. The half life data for HCV in chronically infected patients are remarkably similar to recently published data on human immunodeficiency virus type 1 (HIV-1) suggesting that both RNA viruses replicate continuously and highly productive in vivo . The turnover rates explain the rapid generation of viral diversity and the opportunity for viral escape phenomena from the host immune surveillance.
Prolonged wheezing and tracheal compression caused by an aberrant right subclavian artery.
Authors: C H Maayan, P Mogle, A Tal, S Godfrey
Journal: Thorax (1981)

Compression of the trachea and the oesophagus by anomalous development of the aorta or its branches is well recognised as a cause of airway obstruction.'Right aberrant subclavian artery is one of the anomalies which allegedly does not usually cause any respiratory difficulty.2 3We report a patient with right aberrant subclavian artery who had persistent respiratory difficulties from one week of age, in whom bronchoscopy revealed marked tracheal compression. Case reportThe patient was a 6-month-old boy, the only child of a healthy 24-year-old mother and a 25-year-old father who suffers from asthma.He was born at term weighing
Abstract OT2-3-03: <u>D</u>enosumab versus placebo as adjuvant treatment for women with early-stage breast <u>ca</u>ncer at high risk of disease <u>re</u>currence (D-CARE): An international, randomized, double-blind, placebo-controlled phase 3 clinical trial
Authors: PE Goss, CH Barrios, A Chan, DM Finkelstein, H Iwata, M Martin, A Braun, C Ke, T Maniar, RE Coleman
Journal: Cancer Research (2012)

Abstract Bone represents approximately 40% of all first recurrences in women with early-stage breast cancer and is a common site of distant recurrence. In preclinical studies, RANKL inhibition significantly delays skeletal tumor formation, reduces skeletal tumor burden, and prolongs survival of tumor-bearing mice. Denosumab is approved for the prevention of skeletal-related events (SREs) in patients with established bone metastases from solid tumors. Purpose: The D-CARE trial is designed to assess if denosumab treatment prolongs bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. The primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Additional endpoints are safety, breast density, incidence of SREs (following the development of bone metastasis) patient reported outcomes, and biomarkers. Methods: In this international, randomized, double-blind, and placebo controlled phase 3 trial, approximately 4,500 women with stage II or III breast cancer, at high risk for recurrence and with known hormone and HER-2 receptor status, are eligible. High risk is defined as biopsy evidence of breast cancer in regional lymph nodes, tumor size &amp;gt; 5 cm, (T3), or locally advanced disease (T4). Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination, must be planned. Patients with a prior history of breast cancer (except ductal carcinoma in situ or lobular carcinoma in situ) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization, or any intravenous BP use, are not eligible. Patients are randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. Supplemental vitamin D (≥ 400 IU) and calcium (≥ 500 mg) will be administered. The trial, sponsored by Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154, began enrolling patients in June 2010 and is expected to complete enrollment in late 2012. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-3-03.
Roles of Ca <sup>2+</sup> and Crossbridge Kinetics in Determining the Maximum Rates of Ca <sup>2+</sup> Activation and Relaxation in Rat and Guinea Pig Skinned Trabeculae
Authors: Sue Palmer, Jonathan C. Kentish
Journal: Circulation Research (1998)

Abstract —We examined the influences of Ca 2+ and crossbridge kinetics on the maximum rate of force development during Ca 2+ activation of cardiac myofibrils and on the maximum rate of relaxation. Flash photolysis of diazo-2 or nitrophenyl-EGTA was used to produce a sudden decrease or increase, respectively, in [Ca 2+ ] within Triton-skinned trabeculae from rat and guinea pig hearts (22°C). Trabeculae from both species had similar Ca 2+ sensitivities, suggesting that the rate of dissociation of Ca 2+ from troponin C ( k off ) is similar in the 2 species. However, the rate of relaxation after diazo-2 photolysis was 5 times faster in the rat (16.1±0.9 s −1 , mean±SEM, n=11) than in the guinea pig (2.99±0.26 s −1 , n=7). This indicates that the maximum relaxation rate is limited by crossbridge kinetics rather than by k off . The maximum rates of rapid activation by Ca 2+ after nitrophenyl-EGTA photolysis ( k act ) and of force redevelopment after forcible crossbridge dissociation ( k tr ) were similar and were ≈5-fold faster in rat ( k act =14.4±0.9 s −1 , k tr =13.0±0.6 s −1 ) than in guinea pig ( k act =2.57±0.14 s −1 , k tr =2.69±0.30 s −1 ) trabeculae. This too may be mainly due to species differences in crossbridge kinetics. Both k act and k tr increased as [Ca 2+ ] increased. This Ca 2+ dependence of the rates of force development is consistent with current models for the Ca 2+ activation of the crossbridge cycle, but these models do not explain the similarity in the maximal rates of activation and relaxation within a given species.
A very public death
Authors: N. Craft
Journal: BMJ (1997)

I have often wondered what I would do if I had just been told that I had only a short time left to live. Perhaps I would spend all my savings in one last hedonistic fling. Or perhaps I would spend the time organising my affairs to ease the administrative burden on the executors of my will. I imagine that it is more likely that I would simply decline into despondency. All these are predictable responses. Far less expected is the response of a growing group of people who, when faced with this news, choose to offer their experience for public scrutiny by writing a personal account of their illness and publishing it in a newspaper or magazine.

In the past year many of us will have read Clare Vaughan's compelling Personal View in the BMJ in which she describes her response to having disseminated breast cancer ( BMJ 1996;313:565). Martyn Harris's “On the Sick” columns in the Spectator and the Daily Telegraph , which record his experiences of lymphoma, and Oscar Moore's PWA column (person with AIDS) in the Guardian provide further examples of the …
Is there an emergent need to modify the desmoglein compensation theory in pemphigus on the basis of Dsg ELISA data and alternative pathogenic mechanisms?
Authors: K. Sardana, V.K. Garg, P. Agarwal
Journal: British Journal of Dermatology (2012)

Journal Article Is there an emergent need to modify the desmoglein compensation theory in pemphigus on the basis of Dsg ELISA data and alternative pathogenic mechanisms? Get access K. Sardana, K. Sardana Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India E‐mail: kabirijdvl@gmail.com Search for other works by this author on: Oxford Academic Google Scholar V.K. Garg, V.K. Garg Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India E‐mail: kabirijdvl@gmail.com Search for other works by this author on: Oxford Academic Google Scholar P. Agarwal P. Agarwal Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India E‐mail: kabirijdvl@gmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 3, 1 March 2013, Pages 669–674, https://doi.org/10.1111/bjd.12012 Published: 01 March 2013
Volume of Graft and Native Lung after Single-Lung Transplantation for Emphysema
Authors: MARC ESTENNE, MARIE CASSART, PHILIPPE PONCELET, PIERRE ALAIN GEVENOIS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

To assess how the presence of the hyperinflated native lung influences the volume of the graft after single-lung transplantation (SLT) for emphysema, we used chest computed tomography to measure the TLC of each lung at a mean of 326 d before and 239, 588, and 932 d after SLT in nine patients. In addition, we obtained measurements of TLC and FRC in these nine patients plus one additional recipient at 697 d after surgery, and in 10 nonsmoking normal subjects matched for age, sex, height, and weight. On the nontransplanted side, TLC averaged 3.57 L before and 3.73 L, 3.70 L, and 3.73 L after SLT (NS). Corresponding values on the transplanted side were 3.42 L before and 2.06 L, 1.96 L, and 1.90 L after surgery, respectively (p < 0.0002). Compared with the values obtained on the ipsilateral side in the control subjects, the FRC of the graft amounted to 100%, but its TLC was decreased to 79% (p < 0.005). We conclude that (1) the TLC of the graft and of the native lung do not change over time after SLT for emphysema, and (2) compared with the ipsilateral lung in normal control subjects, the TLC of the graft is substantially reduced, but its FRC is within normal limits.
John Neville Ormrod
Authors: G. Munton
Journal: BMJ (2009)

John Neville Ormrod, former consultant ophthalmic surgeon in Maidstone, Kent, passed away peacefully at his home in Sutton Valence, Kent, on Friday 16 October 2009, aged 86.

John will be remembered by staff and many patients and their relatives as consultant ophthalmic surgeon at Kent County Ophthalmic and Aural Hospital, Maidstone, from 1956 to 1983. A very reserved man, he was highly respected by his patients and his colleagues as he demanded of himself the highest standards personally and in the diagnosis, treatment, and surgery of eye diseases. He always did what he knew to be right. He also demonstrated that essential mark of the surgeon, tenacity.

John qualified MB ChB with …
The effect of immunotherapy on humoral and cellular responses in ragweed hayfever.
Authors: R Evans, H Pence, H Kaplan, R E Rocklin
Journal: Journal of Clinical Investigation (1976)

The effect of specific immunotherapy on several in vitro responses to ragweed antigen E has been evaluated in 17 atopic patients with ragweed hayfever. The methods employed were leukocyte histamine release, measurement of specific IgE anti-ragweed antibody and specific IgG anti-ragweed antibody, lymphocyte proliferation, and the production of two lymphocyte mediators (migration inhibitory factor and mitogenic factor). The duration of treatment and symptom improvement were also recorded for comparison. Immunotherapy was associated with a decrease in leukocyte sensitivity for histamine release to ragweed antigen E in a majority of the patients. In addition, there was a significant decrease in IgE anti-ragweed antibody and a significant increase in IgG anti-ragweed antibody. Immunotherapy also resulted in a significant decrease in lymphocyte responsiveness to ragweed antigen E as measured by proliferation and the production of mediators. Symptomatic improvement was best correlated with the presence of IgG anti-ragweed antibody responses. The production of this antibody was also associated with a decrease in lymphocyte responsiveness. The results of this study indicate that specific immunotherapy in ragweed-sensitive patients induces alterations in immunologic reactivity to ragweed antigen in vitro. This response is antigen specific, includes elements of both humoral and cellular immunity, and may account for the clinical improvement that is often observed in patients who undergo this form of therapy.
ESTIMATION OF CARDIAC AREA IN CHILDREN
Authors: PAUL C. HODGES
Journal: JAMA (1933)

Many years ago Bardeen introduced in this country a technic for measuring the size of the heart by means of long-distance roentgenograms. Four points are involved: A knowledge of the approximate amount of triangular distortion remaining even for distances of 2 meters or greater. This is usually less than 5 per cent. A method of drawing in, more or less arbitrarily, the upper and lower borders, thus completing the outline of an area bounded on either side by the edges of the heart silhouetted against air-containing lung. Adaptation of a simple engineering instrument for the measurement of the area thus outlined. The establishment of tables showing the normal range of the relationship between this area and certain body measurements in normal subjects. Nine years ago one of us, working with Eyster at the University of Wisconsin, amplified Bardeen's tables of the normal size of the heart of adults by developing
Reversal of Cardiac Hypertrophy and Fibrosis From Pressure Overload by Tetrahydrobiopterin
Authors: An L. Moens, Eiki Takimoto, Carlo G. Tocchetti, Khalid Chakir, Djahida Bedja, Gianfranco Cormaci, Elizabeth A. Ketner, Maulik Majmudar, Kathleen Gabrielson, Marc K. Halushka, James B. Mitchell, Shyam Biswal, Keith M. Channon, Michael S. Wolin, Nicholas J. Alp, Nazareno Paolocci, Hunter C. Champion, David A. Kass
Journal: Circulation (2008)

Sustained pressure overload induces pathological cardiac hypertrophy and dysfunction. Oxidative stress linked to nitric oxide synthase (NOS) uncoupling may play an important role. We tested whether tetrahydrobiopterin (BH4) can recouple NOS and reverse preestablished advanced hypertrophy, fibrosis, and dysfunction.C57/Bl6 mice underwent transverse aortic constriction for 4 weeks, increasing cardiac mass (190%) and diastolic dimension (144%), lowering ejection fraction (-46%), and triggering NOS uncoupling and oxidative stress. Oral BH4 was then administered for 5 more weeks of pressure overload. Without reducing loading, BH4 reversed hypertrophy and fibrosis, recoupled endothelial NOS, lowered oxidant stress, and improved chamber and myocyte function, whereas untreated hearts worsened. If BH4 was started at the onset of pressure overload, it did not suppress hypertrophy over the first week when NOS activity remained preserved even in untreated transverse aortic constriction hearts. However, BH4 stopped subsequent remodeling when NOS activity was otherwise declining. A broad antioxidant, Tempol, also reduced oxidant stress yet did not recouple NOS or reverse worsened hypertrophy/fibrosis from sustained transverse aortic constriction. Microarray analysis revealed very different gene expression profiles for both treatments. BH4 did not enhance net protein kinase G activity. Finally, transgenic mice with enhanced BH4 synthesis confined to endothelial cells were unprotected against pressure overload, indicating that exogenous BH4 targeted myocytes and fibroblasts.NOS recoupling by exogenous BH4 ameliorates preexisting advanced cardiac hypertrophy/fibrosis and is more effective than a less targeted antioxidant approach (Tempol). These data highlight the importance of myocyte NOS uncoupling in hypertrophic heart disease and support BH4 as a potential new approach to treat this disorder.
ERYTHEMA MULTIFORME FOLLOWING VACCINATION.
Authors: LOUIS M. WARFIELD
Journal: JAMA (1905)

Considering the great number of persons vaccinated, the comparatively few complicating eruptions that occur is not a little surprising. As has been often remarked, many eruptions occurring in the course of a vaccination period are undoubtedly accidental, while others are undoubtedly due to the vaccine virus. A condition sufficiently interesting to report came under my notice not long ago. <h3>Patient.</h3> —Miss J. H., aged 23, a trained nurse, had never been vaccinated previously, and has always enjoyed exceptional health. Her appetite and digestion are good and menstruation regular. She had had the usual mild children's diseases when young, but had never had any eruptions. For about a year she has been very slightly troubled with constipation. Previous to her vaccination she had been in perfect health and had no gastrointestinal disturbance nor any symptoms of even a mild illness. <h3>Vaccination and Result.</h3> —She was vaccinated July 29 on the upper
RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion
Authors: Jun Ding, Jaime N Guzman, Tatiana Tkatch, Songhai Chen, Joshua A Goldberg, Philip J Ebert, Pat Levitt, Charles J Wilson, Heidi E Hamm, D James Surmeier
Journal: Nature Neuroscience (2006)
Initiating and Withdrawing Life Support
Authors: J E Ruark, T A Raffin
Journal: New England Journal of Medicine (1988)

DURING the past century, dramatic changes have occurred in physicians' ability to prolong life. A hundred years ago, little more than rudimentary supportive care could be offered to most critically ill patients. Doctors now choose from a vast array of interventions that, when combined with effective therapies for underlying conditions, often greatly prolong survival. Unfortunately, the quality of the additional life so skillfully sought can range from marginally tolerable to positively miserable.These considerations underscore the importance of a clear ethical framework for making decisions about the initiation and withdrawal of all medical treatments. This paper considers basic and advanced . . .
cAMP-mediated -fos expression in pressure-overloaded acceleration of protein synthesis in adult rat heart
Authors: J OSAKI, T HANEDA, H SAKAI, K KIKUCHI
Journal: Cardiovascular Research (1997)

The aim was to determine whether proto-oncogene c-fos expression and acceleration of protein synthesis by acute pressure overload to the heart were coupled with a cAMP- and protein-kinase-A-dependent system in adult rat heart.Isolated adult rat hearts were perfused as Langendorff preparations at a constant aortic pressure of 60 mmHg. In the pressure-overloaded group, aortic pressure was raised from 60 to 120 mmHg for the time indicated. Agents that increase cAMP were added to the perfusate at an aortic pressure of 60 mmHg. Furthermore, a selective protein kinase A inhibitor (H-89) or a selective protein kinase C inhibitor (calphostin C) was administered before the elevation of aortic pressure or the addition of the agents. cAMP content or rates of protein synthesis were measured by RIA or the incorporation of [14C]phenylalanine into total heart protein, respectively. c-fos mRNA expression was determined by Northern blot analysis.Elevation of aortic pressure in beating hearts and arrested hearts increased cAMP content at 2 min of perfusion by 36 and 41%, induced c-fos mRNA expression at 30-60 min of perfusion by 4.8- and 2.0-fold, and accelerated rates of protein synthesis during the 2nd hour of perfusion by 39 and 41% over control levels, respectively. Glucagon, forskolin or IBMX mimicked increases in these parameters by elevated aortic pressure. H-89 prevented these changes by elevated pressure overload or exposure to forskolin or IBMX in arrested hearts. On the other hand, calphostin C prevented the pressure-induced increases in c-fos expression and protein synthesis rates in arrested hearts.These results suggest that c-fos expression induced by acute pressure overload may be coupled with increased cAMP content and protein kinase A activity in addition to increased protein kinase C activity in adult rat heart.
Use of Long-Acting β-Agonists and Inhaled Corticosteroids
Authors: Jeffrey Glassroth
Journal: Annals of Internal Medicine (2006)

Letters7 November 2006Use of Long-Acting β-Agonists and Inhaled CorticosteroidsJeffrey Glassroth, MDJeffrey Glassroth, MDTufts University School of Medicine, Boston, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-9-200611070-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: Dr. Ernst and colleagues (1) and I agree that inhaled corticosteroids are the appropriate first-line agent for chronic asthma management and that long-acting β-agonists (LABAs) are a valuable next level of treatment for many patients. We seem to disagree on exactly how best to use LABAs. Dr. Ernst and colleagues note that the “greatest benefit from inhaled corticosteroids occurs with low doses” and imply that the need for higher doses will be obviated by early addition of LABAs. In fact, the Gaining Optimal Asthma Control (GOAL) study found that while asthma control could be attained more rapidly ...References1. Ernst P, McIvor A, Ducharme FM, Boulet LP, FitzGerald M, Chapman KR, et al. Safety and effectiveness of long-acting inhaled β-agonist bronchodilators when taken with inhaled corticosteroids. Ann Intern Med. 2006;145:692-4. LinkGoogle Scholar2. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004;170:836-44. [PMID: 15256389] CrossrefMedlineGoogle Scholar3. Martinez FD. Safety of long-acting beta-agonists [Letter]. N Engl J Med. 2006;354:1207-8. Google Scholar4. Suissa S, Baltzan M, Kremer R, Ernst P. Inhaled and nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med. 2004;169:83-8. [PMID: 14551165] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Tufts University School of Medicine, Boston, Massachusetts.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 November 2006Volume 145, Issue 9Page: 710KeywordsAsthmaCataractsConflicts of interestHip fracturesPatients ePublished: 7 November 2006 Issue Published: 7 November 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dysphagia Caused by Elongation and Tortuosity of the Common Carotid Artery
Authors: Edward D. Coppola
Journal: New England Journal of Medicine (1964)

BUCKLING of the major arteries in the neck and mediastinum was described during the last century by Coulson1 (1852) and by Balfour2 (1898), but not until the introduction of contrast angiography did this clinical entity become more widely recognized.3 Ouattlebaum and his associates4 recently indicted elongation and kinking of the internal carotid artery as a cause of transient stroke, although the anatomic abnormality may be found also in the absence of neurologic symptoms. On occasion other vascular malformations in this region, such as arterial aneurysms5 and anomalies of the aortic arch, may give rise to symptoms of dysphagia by externally . . .