tbuckley/cabot-search huggingface dataset:
Phase 2b Trial of Interferon-free Therapy for Hepatitis C Virus Genotype 1
Authors: Kris V. Kowdley, Eric Lawitz, Fred Poordad, Daniel E. Cohen, David R. Nelson, Stefan Zeuzem, Gregory T. Everson, Paul Kwo, Graham R. Foster, Mark S. Sulkowski, Wangang Xie, Tami Pilot-Matias, George Liossis, Lois Larsen, Amit Khatri, Thomas Podsadecki, Barry Bernstein
Journal: New England Journal of Medicine (2014)

An interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection. The addition of another potent agent, the NS5A inhibitor ABT-267, may improve efficacy, especially in difficult-to-treat patients. This study was designed to evaluate multiple regimens of direct-acting antiviral agents and ribavirin in patients with HCV genotype 1 infection who had not received therapy previously or who had no response to prior therapy with pegylated interferon and ribavirin.In this phase 2b, open-label study with 14 treatment subgroups, 571 patients without cirrhosis who had not received treatment previously or who had not had a response to prior therapy were randomly assigned to a regimen of ABT-450/r, combined with ABT-267 or ABT-333 or both, for 8, 12, or 24 weeks and received at least one dose of therapy. All the subgroups but 1 also received ribavirin (dose determined according to body weight). The primary end point was sustained virologic response at 24 weeks after the end of treatment. The primary efficacy analysis compared rates between previously untreated patients who received three direct-acting antiviral agents and ribavirin for 8 weeks and those who received the same therapy for 12 weeks.Among previously untreated patients who received three direct-acting antiviral agents (with the ABT-450/r dose administered as 150 mg of ABT-450 and 100 mg of ritonavir) plus ribavirin, the rate of sustained virologic response at 24 weeks after treatment was 88% among those who received the therapy for 8 weeks and 95% among those who received the therapy for 12 weeks (difference, -7 percentage points; 95% confidence interval, -19 to 5; P=0.24). The rates of sustained virologic response across all treatment subgroups ranged from 83 to 100%. The most frequent adverse events were fatigue, headache, nausea, and insomnia. Eight patients (1%) discontinued treatment owing to adverse events.In this phase 2b study, all-oral regimens of antiviral agents and ribavirin were effective both in patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy. (Funded by AbbVie; ClinicalTrials.gov number, NCT01464827.).
ROENTGEN-RAY THERAPY TWENTY YEARS AGO
Authors: WILLIAM ALLEN PUSEY
Journal: JAMA (1923)

As I see, now and again, reports on treatment of various diseases with roentgen rays and radium, my mind reverts to the time, twenty years ago, when we were learning the therapeutic use of roentgen rays. It has been interesting to me to compare the results then with the results now, and I thought it might be interesting for us to look over some of these old results and compare the present with the past in this field. I began the therapeutic use of roentgen rays, Feb. 1, 1900, in a case of hypertrichosis. Soon after, in treating a case of hypertrichosis, I was amazed to see a bad acne clear up. In May, 1900, I treated my first case of lupus. In December, 1899, Stenbeck had demonstrated before the Swedish Medical Society a case of cured epithelioma, and about the middle of 1900, Johnson and Merrill had published the
The Effect of Selected Variables on the Stability of 99mTc-Sestamibi
Authors: Madhur P. Vaidya, William B. Hladik, Dorothy R. Pathak, Jerry L. Born, Timothy R. Carroll, Dennis Eshima
Journal: Clinical Nuclear Medicine (1996)

Vaidya, Madhur P.1; Hladik, William B.2; Pathak, Dorothy R.3; Born, Jerry L.2; Carroll, Timothy R.4; Eshima, Dennis5 Author Information
CYSTOMA OF THE ARYTENOID REGION OF THE LARYNX, WITH THE REPORT OF A CASE.Read before the Section of Laryngology of the Tenth International Medical Congress, Berlin, 1890.
Authors: W. E. CASSELBERRY
Journal: JAMA (1891)

As the patient will necessarily remain in bed for a considerable time the opening should be made far back on the side to allow free drainage.The tube may be kept in place by a safety pin passed through its outer end and fastened to an adhesive strip.An absorbent compress and bandage will not only take up the pus which will continue to come away for some time, but will prevent the exit and entrance of air during respiration.That the operation is justifiable is shown by the record.In 1881 Fenger and Hollister reported six cases, one of which, their own, recovered, and Ruenberg {London Medical Record, 1887) collated eleven cases of abscess.Two recovered and in three cases the diagnosis was doubtful.In the three fatal cases death could not be attributed to the surgical operation.In seventeen cases of gangrene collected from medical literature, where pneumotomy was performed, seven recovered more or less completely {Annual of Medical Science, 1888).Permit me to offer an abstract of the history of two cases of gangrenous abscess of the lung seen during the last year.Case 1.-Mrs.G., of North Eighteenth street, a young married lady of good family history.I first saw her in March, 1890, in consultation with her family physician, Dr. A. S. Barnes.The statement was made that she had not been well since th* birth of her child some months
Ex vivo analysis of cytotoxic T lymphocytes to measles antigens during infection and after vaccination in Gambian children.
Authors: A Jaye, A F Magnusen, A D Sadiq, T Corrah, H C Whittle
Journal: Journal of Clinical Investigation (1998)

The study of cytotoxic T cell responses to measles antigens during infection and after vaccination may provide insight into the immunopathology of the infection. It will also provide a knowledge of the immunity conferred by wild or attenuated virus, which will help in the design of new vaccines. Direct cytotoxic T cell responses, which did not require in vitro restimulation, were measured from peripheral blood by a standard 51Cr-release assay in 35 patients with acute measles, using HLA class I matched allogeneic B cells as targets. 77% showed specific responses to measles fusion protein, 69% to the hemagglutinin, and 50% to the nucleoprotein. These responses, which were related to severity of disease and history of previous vaccination, had waned by 14-24 wk after measles when memory responses to the same antigens could be elicited by restimulation in 71% of the 13 patients tested. A similar pattern followed vaccination: direct cytotoxic responses to fusion and hemagglutinin proteins were shown in 70% of the 20 children tested while 50% responded to the nucleoprotein. These responses, which were mediated by both CD8(+) and CD4(+) cells, faded over 6 wk when memory responses could be restimulated. Thus, a vigorous cytotoxic T lymphocyte response to fusion, hemagglutinin, and nucleoproteins is important in both natural and vaccine-induced immunity to measles.
653. The Controlled Transgene Expression in Oncolytic Adenoviral Vectors with Major Late Promoter for Therapy of Cancer
Authors: Wei Jiang, Rong Cai, Guanghua Yang, Kai Chen, Yu Chen, Xinyuan Liu, Cheng Qian
Journal: Molecular Therapy (2006)

Virotherapy with oncolytic viruses is based on the use of tumor specific replicating virus. The oncolytic viruses have capacity for destruction of tumors and produce new infectious virus particles that will infect surrounding tumor cells and spread throughout the tumor. They have been used as potential vectors to express therapeutic genes in tumor cells. In order to allow transgene expression in the controlled and predicted manner, we generated oncolytic adenoviral vectors with transgene driven by major late promoter (MLP). The reporter gene HcRed and therapeutic genes Mda7/IL-24 and TRAIL have been incorporated into this vector. Our data showed that transgene expression was not detectable in the first hours after infection. The high level of transgene expression was found at 24 and 48 hours after infection. The expression level of transgenes was dramatic higher in tumor cells than normal cells infected with our vectors. Our results supported that high level of transgene expression in tumor cells was due to the viral replication. The vector carrying therapeutic genes have strong cytotoxicity to tumor cells. Our data indicated that oncolytic adenovirus could serve as potent vectors for delivery of therapeutic gene into tumor cells.
Prevalence of Fabry Disease in Female Patients With Late-Onset Hypertrophic Cardiomyopathy
Authors: Cristina Chimenti, Maurizio Pieroni, Emanuela Morgante, Daniela Antuzzi, Andrea Russo, Matteo Antonio Russo, Attilio Maseri, Andrea Frustaci
Journal: Circulation (2004)

Fabry disease (FD) has been recognized as the cause of left ventricular hypertrophy in 6% of men with late-onset hypertrophic cardiomyopathy (HCM). Although FD is considered a recessive X-linked disorder, affected women are increasingly reported. The aim of our study was to determine the prevalence of FD in female patients with HCM.Thirty-four consecutive women (mean age, 50+/-13.6 years) who received an ECG and echocardiographic diagnosis of HCM were submitted to an invasive cardiac study that included a biventricular endomyocardial biopsy. Tissue samples were analyzed for histology and electron microscopy. Peripheral blood activity of alpha-galactosidase (alpha-Gal) A was assessed in all patients. None of them had a family history of FD. Histology and electron microscopy showed in 4 patients (12%; mean age, 51.5+/-3.9 years) the presence of cell vacuoles characterized by the accumulation of glycolipid material organized in concentric lamellar structures, diagnostic for FD. In the remaining patients, histology was consistent with HCM. In all the female carriers, the heart was the only organ clinically involved in the disease, showing concentric hypertrophy in 2 patients, asymmetric hypertrophy in 1, and apical hypertrophy in 1. The alpha-Gal A enzymatic activity was 44+/-14% of control values. Genetic analysis showed the presence of alpha-Gal A gene mutation in all 4 cases.FD may account for up to 12% of females with late-onset HCM. Those heterozygous for FD with left ventricular hypertrophy are potential candidates for enzyme enhancement/replacement therapy.
Prevalence and characteristics of disproportionate ventricular septal thickening in patients with acquired or congenital heart diseases: echocardiographic and morphologic findings.
Authors: B J Maron, C E Clark, W L Henry, T Fukuda, J E Edwards, E C Mathews, D R Redwood, S E Epstein
Journal: Circulation (1977)

Echocardiographic and necropsy studies were performed in 304 patients with various cardiac diseases. The overall prevalence of disproportionate ventricular septal thickening (septal to free wall ratio greater than or equal to 1.3) was 10%. However, it was related to the type of cardiac lesion. Prevalence was high (greater than 20%) in pulmonary stenosis or primary pulmonary hypertension, lower (less than 15%) in Eisenmenger syndrome or aortic or mitral valvular disease and was not present in atrial or ventricular septal defect. In right ventricular overload, prevalence of disproportionate septal thickening correlated with increasing ventricular systolic pressure. None of 16 patients with disproportionate septal thickening studied at necropsy showed marked disorientation of cardiac muscle cells in the ventricular septum, characteristic of genetically transmitted asymmetric septal hypertrophy (ASH). Furthermore, disproportionate septal thickening was demonstrated by echocardiography in only one of 59 first degree relatives of patients with disproportionate septal thickening and associated cardiac diseases. Thus, disproportionate ventricular septal thickening associated with other cardiac diseases usually is due to secondary hypertrophy and is not a manifestation of genetically transmitted ASH.
Transverse myelitis occurring during pregnancy in a patient with systemic lupus erythematosus.
Authors: M Marabani, A Zoma, D Hadley, R D Sturrock
Journal: Annals of the Rheumatic Diseases (1989)

Myelopathy is a well recognised but infrequent neurological manifestation of systemic lupus erythematosus (SLE). The case of a 27 year old woman with SLE of seven years9 duration who developed a spastic paraparesis during her second pregnancy is reported. Magnetic resonance imaging did not show any intrinsic abnormality of the spinal cord. Anticardiolipin antibody was weakly positive and C4 was low. The patient responded dramatically to steroids.
STUDIES OF CONGENITAL HEART DISEASE. III. VENOUS CATHETERIZATION AS A DIAGNOSTIC AID IN PATENT DUCTUS ARTERIOSUS, TETRALOGY OF FALLOT, VENTRICULAR SEPTAL DEFECT, AND AURICULAR SEPTAL DEFECT 1
Authors: L. Dexter, F. W. Haynes, C. S. Burwell, E. C. Eppinger, M. C. Sosman, J. M. Evans
Journal: Journal of Clinical Investigation (1947)
Slc26a6 functions as an electrogenic Cl−/HCO3− exchanger in cardiac myocytes
Authors: Hyo Jeong Kim, Richard Myers, Choong-Ryoul Sihn, Sassan Rafizadeh, Xiao-Dong Zhang
Journal: Cardiovascular Research (2013)

AimsAlterations in cardiac acid–base balance can produce profound impact on excitation–contraction coupling and precipitate cardiac dysfunction and arrhythmias. A member of the solute carrier (SLC) family, Slc26a6, has been shown to be a chloride-hydroxyl exchanger and the predominant chloride-bicarbonate exchanger in the mouse heart. However, the exact isoforms and functional characteristics of cardiac Slc26a6 remain unknown. The objective of the present study is to determine the molecular identity of cardiac Slc26a6 isoforms, to examine their cellular expressions in the heart, and to test the function of Slc26a6 in cardiomyocytes.
Mutations in the nonstructural 5A gene of European hepatitis C virus isolates and response to interferon alfa
Authors: S Zeuzem, J H Lee, W K Roth
Journal: Hepatology (1997)

The response rate to interferon alfa (IFN–α) in patients infected with hepatitis C virus (HCV) genotype 1 isolates is poor. A region associated with sensitivity to IFN has been identified in subtype HCV– 1b isolates from Japanese patients in the carboxyterminal half of the nonstructural protein NS5A (between codon 2209 and 2248). HCV–1b isolates with at least four amino acid changes in this region compared with the HCV–1b prototype sequence were sensitive, whereas isolates identical to the prototype sequence were resistant to IFN–α. Patients infected with HCV–1b isolates carrying 1 to 3 mutations in NS5A2209–2248 showed an intermediate response pattern. Because of the large geographical differences observed for HCV it is unknown whether this putative IFN–α sensitivity determining region is also predictive for European isolates. We analyzed 32 patients chronically infected with HCV–1a or HCV–1b isolates who were treated with 3 million units of recombinant IFN–α three times per week for 1 year. Before initiation, during, and after treatment serum HCV–RNA levels were assessed by a quantitative reverse–transcription polymerase chain reaction (RT–PCR) assay. The amino acid sequence of NS5A2209–2248was determined by direct sequencing of the PCR–amplified HCV genome and was compared with the reference sequence HCV–J. In patients chronically infected with subtype HCV–1a or HCV–1b the initial or sustained response to IFN–α was not related to the number of amino acid substitutions in the NS5A2209–2248 region. In addition, the number of amino acid changes in NS5A2209–2248 was not related to pretreatment HCV–RNA serum levels. In three patients with a pronounced initial decline of HCV–RNA levels (&gt; 3 log) sequence analyses of NS5A2209–2248 were performed before and after therapy. Compared with the pretreatment amino acid sequence the HCV isolates of these patients revealed more mutations in the NS5A2209–2248 region after therapy. These findings from European patients indicate that the NS5A2209–2248 region of HCV does not represent a common interferon sensitivity determining region.
Noradrenergic inhibition of canine gallbladder contraction and murine pancreatic secretion during stress by corticotropin-releasing factor.
Authors: H J Lenz, B Messmer, F G Zimmerman
Journal: Journal of Clinical Investigation (1992)

Gastrointestinal secretory and motor responses are profoundly altered during stress; but the effects of stress and its mediator(s) on the two major gut functions, exocrine pancreatic secretion and gallbladder motility, are unknown. We therefore developed two animal models that allowed us to examine the effects of acoustic stress on canine gallbladder contraction and restraint stress on rat exocrine pancreatic secretion. Acoustic stress inhibited cholecystokinin-8 (CCK)- and meal-induced gallbladder contraction, and restraint stress inhibited basal and CCK/secretin-stimulated pancreatic secretion. These inhibitory responses were mimicked by cerebral injection of corticotropin-releasing factor (CRF) and abolished by the CRF antagonist, alpha-helical CRF-(9-41). The effects of stress and exogenous CRF were simulated by intravenous infusion of norepinephrine but prevented by ganglionic, noradrenergic, and alpha-adrenergic but not beta-adrenergic receptor blockade. Vagotomy, adrenalectomy, and--in rats--hypophysectomy did not alter the effects produced by stress and CRF. These results indicate that endogenous CRF released in response to different stressors in distinct species inhibits canine gallbladder contraction and murine exocrine pancreatic secretion via activation of sympathetic efferents. Release of norepinephrine appears to be the final common pathway producing inhibition of biliary and pancreatic digestive function during stress mediated by cerebral CRF.
Role of cysteine proteases and protease inhibitors in gastric mucosal damage induced by ethanol or ammonia in the rat.
Authors: L Nagy, S Kusstatscher, P V Hauschka, S Szabo
Journal: Journal of Clinical Investigation (1996)

Since recent studies suggest an imbalance between cathepsin B and its tissue protease inhibitors (PI) in the pathogenesis of acute and chronic diseases, we tested the hypothesis that release of activated cysteine proteases (P) such as cathepsins B, H, and L might play a role in the pathogenesis of gastric hemorrhagic mucosal lesions (HML) induced by ethanol (E) or ammonia (A). Anesthetized rats received 1 ml of 50% E or 1% A solution intragastrically for 1 min during in situ gastric luminal perfusion. Rapid activation and release of cathepsins B, L, and H into the luminal perfusate preceded the formation of HML quantified by planimetry. Mucosal presence and activity of cysteine PI and cathepsin B have also been investigated in the pathogenesis of chemically induced HML. We extracted and partially isolated acid and thermostable inhibitors of cathepsin B in the gastric mucosa, and found rapid inactivation of PI and activation of cathepsin B in the early phase of E- or A-induced HML. Negative correlations were found between P and PI activities by E or A solutions. Both the activation of cathepsins B, L, and H and the development of E-induced HML were prevented by pretreatment with the sulfhydryl alkylator N-ethylmaleimide. These results suggest that cysteine P may be activated in the rat stomach after E or A exposure, and cysteine P may have a role in the pathogenesis of E- or A-induced gastric HML. Endogenous PI may also participate in the mechanisms of gastric mucosal lesions and gastroprotection.
The circadian clock functions as a potent regulator of allergic reaction
Authors: A. Nakao, Y. Nakamura, S. Shibata
Journal: Allergy (2015)

Abstract Symptoms and laboratory parameters of allergic diseases exhibit prominent ~24‐h variations. For instance, in most allergic rhinitis patients, symptoms worsen overnight or early in the morning. Accordingly, there are benefits to nighttime dosing of anti‐allergy medications in such patients. Although the circadian pathophysiology of allergic diseases is well documented, the biological basis of this phenomenon remains poorly understood. Recent studies have begun to reveal that the internal timekeeping system termed the circadian clock plays a key role in temporal regulation of allergic reaction, and may therefore underlie the circadian pathophysiology of allergic diseases. Here, we review new knowledge that highlights the emerging role of the circadian clock as a potent regulator of allergic reactions. Given the strong influence of circadian rhythms on allergic diseases, we believe that research on how the time of day impacts allergic reaction which we may call ‘chronoallergology’ will provide new insight into previously unknown aspects of the biology of allergies. Such knowledge should facilitate novel strategies for prevention and treatment of these diseases.
Potter's Pathology of the Fetus and Infant
Authors: Jerome B. Taxy
Journal: JAMA (1997)

In the first edition in 1952 of her classic textbook<i>Pathology of the Fetus and Infant</i>, Edith Potter wrote "The pathology of the fetus and young infant has until recently been greatly neglected." By the third edition (1975), she could state that the "condition of the unborn and newly born infant and the processes responsible for its development... are major subjects of investigation and clinical interest," acknowledging a major leap in the years since the first edition. Dr Potter, one of the most diligent and thorough observers of human pathology, succinctly cataloged some 19 000 fetal and neonatal autopsies from several sources, creating a major work, which as of the third edition comprised a single volume of 28 chapters and nearly 700 pages. Lest anyone think that laboring in the autopsy room over macerated stillborns and deceased infants is clinically irrelevant, Potter's classification, for example, of anomalous kidneys and the
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Topical Anaesthesia of the Pharynx in Upper Gastrointestinal Endoscopy
Authors: J. L. Hedenbro, M. Ekelund, O. Jansson, A. Lindblom
Journal: Endoscopy (1992)

Reduction of discomfort during diagnostic upper endoscopy may not be desired by patients if the medication has long-lasting and severe after-effects. The present study was designed to examine whether topical anaesthesia of the pharynx without concomitant sedation is of overall benefit to patients undergoing diagnostic upper endoscopy. Two hundred out-patients were randomized to receive in the form of a pharyngeal spray either 80-120 mg lidocaine or placebo. Patients assessed discomfort on a 100 mm visual analogue scale the day after examination. Patients undergoing endoscopy who received lidocaine spray experienced significantly less discomfort from the intubation (p = 0.0001), and discomfort induced by the rest of the examination was also reduced (p = 0.003). The outcome of the endoscopists' assessment was also in favour of lidocaine spray for intubation (p = 0.157) and ease of examination (p = 0.0014). The assessment of throat discomfort suffered by patients after endoscopy did not differ between the groups. A majority of patients, the same proportion in each group, stated they would prefer their next endoscopy to be performed with topical anaesthesia.