tbuckley/cabot-search huggingface dataset:
REG endpoint validation: Association between database and patient-reported exacerbations
Authors: Richard Martin, Alex Dima, Annie Burden, Emilio Pizzichini, Guy Brusselle, Janet Holbrook, Nikolaos G. Papadopoulos, Todor Popov, Gene Colice, Helen Reddel, Julie von Ziegenweidt, Alison Chisholm, David Price
Journal: European Respiratory Journal (2014)

Aim: Patient-reported exacerbations (PRE) can be hard to capture. We assessed whether a database exacerbation measure (DBE) reliably reflected the patient experience.

Methods: We used a UK research database to select clinical and asthma questionnaire records of patients aged 18–60yrs with an asthma diagnosis, no other chronic respiratory diseases and not receiving maintenance oral steroids. DBEs were identified in the clinical records as: a course of oral steroids with evidence of respiratory review (OS) and/or asthma-related hospital admission or emergency room (ER) attendance. PREs over the same period were identified as a positive questionnaire response to any of the 3 questions: In the last 12 months, have you (i)Received courses of OS for worsening asthma? (ii)Been admitted to hospital due to asthma? (iii)Attended ER for asthma? The strength of association between the endpoints was assessed using Kendall's Tau-b (τb).

Results: Of a total of 1666 patients (62% female, 24% current smokers), 25% reported ≥1 PRE, and 10% had ≥1 DBE. Some co-linearity was found between PRE items (i)&(ii). A moderate association was found between DBE and PRE (τb=0.419; p<0.001), the table shows the relationship between the measures.

View this table:

Association between PREs & DBEs





Conclusion: All outcome measures have their limitations. Despite the different sources of measurement error for DBE and PRE definitions (eg. known under-reporting of hospitalisations in UK primary care records), these measures were found to have a moderate positive association.
A Controlled Trial of Intravenous Immune Globulin to Reduce Nosocomial Infections in Very-Low-Birth-Weight Infants
Authors: Avroy A. Fanaroff, Sheldon B. Korones, Linda L. Wright, Elizabeth C. Wright, Ronald L. Poland, Charles B. Bauer, Jon E. Tyson, Joseph B. Philips, William Edwards, Jerold F. Lucey, Charlotte S. Catz, Seetha Shankaran, William Oh
Journal: New England Journal of Medicine (1994)

Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections.
Chronic thromboembolic vasculopathy with exercise induced PH but normal resting haemodynamics
Authors: Matthias Held, Maria Grün, Nic Doppert, Regina Holl, Franziska Walter, Manuela Schmidbauer, Heinrike Wilkens, Hans-Joachim Schäfers, Berthold Jany
Journal: European Respiratory Journal (2014)

Background  Chronic thromboembolic pulmonary hypertension (CTEPH) is defined by chronic thromboembolic vascular obstruction and a mean pulmonary artery pressure (mPAP) of at least 25 mm Hg at rest. It is unclear how to manage symptomatic patients with disturbed lung perfusion due to chronic thromboembolic vascular abnormalities and mPAP below 25 mmHg at rest.  Aims:  To characterize subjects with mismatched chronic thromboembolic pulmonary perfusion abnormalities and mPAP   Methods:  We analyzed functional and haemodynamic parameters of 10 subjects with chronic thromboembolic pulmonary vasculopathy but normal mPAP at rest (CTEVP) and 31 CTEPH subjects.  Results:  CTEVP subjects presented with mPAP at rest of 20 +/- 2 mmHG. mPAP (44 +/-8 mmHg) but not PAWP (8 +/- 4 mmHg) rose under exercise condition. CTEVP subjects showed reduced functional capacity: WHO FC III: 9/10, II 1/10); 76 Watt; VO2 peak (14.8 ml/min/kg; 72 % pred.) Oxygen pulse (101 %) and breathing reserve (30 %) were normal. Dead space ventilation (21%) was elevated. The CTEVP cohort as well as the CTEPH subjects presented with functional signs of disturbed pulmonary perfusion (VE/VCO 2 : 46.0/49.4 (p=0.53); EQO 2 AT: 34.0/37.4 (p=0.27); EQCO 2 AT: 39.2/43.8 (p=0.24) , PETCO 2 AT: 28.0/27.0 mmHg (p=0.63); PaET CO 2  9.3/8.5 mmHg(p=0.58). Only P(A-a)O 2  36.1/52.1 mmHg (p=0.04) was significantly different.  4/10 CTEVP subjects underwent PEA. Following PEA 3 were asymptomatic, 1 improved from WHO FC III to II.  Conclusion:  Subjects with dyspnea and CTEVP but normal mPAP below 25mmHg at rest show similar functional limitations as CTEPH patients and can improve significantly following PEA.
Ultrastructural Transformation of a Murine Leydig-Cell Tumor After Gonadotropin Administration
Authors: William B. Neaves
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Ultrastructural Transformation of a Murine Leydig-Cell Tumor After Gonadotropin Administration Get access William B. Neaves William B. Neaves Department of Cell Biology, The University of Texas Southwestern Medical School, Dallas, Texas 75235 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 4, April 1973, Pages 1069–1073, https://doi.org/10.1093/jnci/50.4.1068 Published: 01 April 1973 Article history Received: 09 January 1973 Accepted: 12 February 1973 Published: 01 April 1973
Adaptation of the hepatitis B virus core protein to CD8+ T‐cell selection pressure
Authors: Helenie Kefalakes, Bettina Budeus, Andreas Walker, Christoph Jochum, Gudrun Hilgard, Andreas Heinold, Falko M. Heinemann, Guido Gerken, Daniel Hoffmann, Joerg Timm
Journal: Hepatology (2015)

Activation of hepatitis B virus (HBV)-specific CD8 T cells by therapeutic vaccination may promote sustained control of viral replication by clearance of covalently closed circular DNA from infected hepatocytes. However, little is known about the exact targets of the CD8 T-cell response and whether HBV reproducibly evades CD8 T-cell immune pressure by mutation. The aim of this study was to address if HBV reproducibly selects substitutions in CD8 T-cell epitopes that functionally act as immune escape mutations. The HBV core gene was amplified and sequenced from 148 patients with chronic HBV infection, and the human leukocyte antigen (HLA) class I genotype (A and B loci) was determined. Residues under selection pressure in the presence of particular HLA class I alleles were identified by a statistical approach utilizing the novel analysis package SeqFeatR. With this approach we identified nine residues in HBV core under selection pressure in the presence of 10 different HLA class I alleles. Additional immunological experiments confirmed that seven of the residues were located inside epitopes targeted by patients with chronic HBV infection carrying the relevant HLA class I allele. Consistent with viral escape, the selected substitutions reproducibly impaired recognition by HBV-specific CD8 T cells.Viral sequence analysis allows identification of HLA class I-restricted epitopes under reproducible selection pressure in HBV core; the possibility of viral escape from CD8 T-cell immune pressure needs attention in the context of therapeutic vaccination against HBV.
Alkylation of Rat Liver RNA by Cyclic &lt;italic&gt;N&lt;/italic&gt;-Nitrosamines &lt;italic&gt;In Vivo&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K. Y. Lee, W. Lijinsky
Journal: JNCI Journal of the National Cancer Institute (1966)

The possibility that the carcinogenic action of cyclic N-nitrosamines is related to their ability to form alkylating agents in vivo was investigated. Three nitrosamines, nitrosopyrrolidine, nitrosomorpholine, and nitrosopiperidine, were labeled with tritium and injected into rats. The rats were killed after a suitable time, the livers were homogenized, and a preparation of RNA was made from each. All the RNA preparations contained tritium. The chromatographic profiles (on an ion-exchange column) of the acid hydrolysates of each RNA revealed the presence of an abnormal, labeled base between guanine and adenine. This base always appeared to be the same. The abnormal base derived from nitrosomorpholine was identified as 7-methylguanine by mass spectrometry.
Collagen Biosynthesis in Human Neuroblastoma Cell Lines: Evidence for Expression of Glial Cell Properties&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Y A DeClerck, C Lee
Journal: JNCI Journal of the National Cancer Institute (1985)

An analysis was done on the synthesis of collagen, an extracellular matrix protein synthesized by Schwann cells, by several human neuroblastoma lines. Cultured cells were incubated in the presence of L-[2,3-3H]proline, and the collagens synthesized and secreted into the culture medium were analyzed by electrophoresis on acrylamide gels, ion exchange chromatography, and immunoprecipitation. The amount of collagen secreted by 4 cell lines tested represented less than 3% of the total protein synthesis, indicating a low degree of collagen biosynthesis by this tumor type. Analysis of collagen types secreted by all cell lines revealed the presence of a high-molecular-weight collagen precursor (Mr = 165,000) identified as type IV procollagen. In addition, several cell lines synthesized stromal type I and type III collagens. These studies show that neuroblastoma cells produce collagenous proteins including basement membrane collagen (type IV) and stromal collagens (types I and III), indicating that these cells express properties of glial cells such as Schwann cells.
Prevalence of asthma and allergies and family's education grade in Japan
Authors: Hiroshi Odajima, Yuko Amimoto, Yoko Murakami, Chikako Motomura
Journal: European Respiratory Journal (2013)

Back ground: ISAAC investigation was conducted in Fukuoka in2002.To carry out the question about a family’s education grade was refused in Japan those days in many cases.  For this reason, the report about the relationship between the family’s education grade and the prevalence of asthma and an allergic diseases is not performed for the report of ISAAC investigation in Japan.After that in the epidemiologic survey in Japan, the report about the relation of the education grade of family and allergy diseases is not found.  In the investigation in 2002, since cooperation to answer about a family9s education grade were kindly obtained at the 11 elementary school, it is investigated again and reported.  Aim: The relationship between the prevalence of asthma and allergic diseases and family’s education grade in Japan is clarified.  Subject and method: Subject are 923, a first grader and a second grader children from 11 elementary school in Fukuoka. They were investigated by the method of ISAAC PHASEIII.  The mothers of 11 children were graduated from junior high school, 251 mothers senior high school, and 482 mothers more than junior college. The number of the mother graduated junior high school was small, so we compared the prevalence between the children whose mother graduated from senior high school and those from junior college.  Results: There were the statistically significant differences between these 2 groups in the prevalence of wheeze of speech disturbance, exercise-induced asthma, and nasal allergy symptoms.  Conclusion: There was a differences in the prevalence of wheeze according to the mother’s education grade in Japan.This tendency was recognized even in Japan as reported by other countries.
Association of Tumor Induction by Ultraviolet Light-Inactivated Adenovirus 2-Simian Virus 40 Recombinants With a Specific Segment of Simian Virus 40 DNA
Authors: Andrew M. Lewis, James L. Cook
Journal: JNCI Journal of the National Cancer Institute (1979)

The nondefective (ND) adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid Ad2+ND4, which contains the segment of the SV40 genome between map positions 0.11 and 0.59, induced tumors in Syrian golden hamsters after inactivation by UV light. Ad2 and the Ad2+ND2 hybrid, which contains the segment of the SV40 genome between map positions 0.11 and 0.43, were not oncogenic after inactivation by UV light. These results showed that the incorporation of a specific segment of SV40 DNA into the Ad2 genome can alter the pathogenesis of the Ad2+ND4 virus by rendering it oncogenic for hamsters.
Chemotherapeutic Sensitivity of Normal and Leukemic Hematopoietic Progenitor Cells to &lt;italic&gt;N&lt;/italic&gt;-[4-(9-Acrldinylamlno)-3-methoxyphenyl]-methanesulfonamlde, a New Anticancer Agent&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: Theodore E. Spiro, Mirellle Socquet, Alain Deiforge, Pierre Stryckmans
Journal: JNCI Journal of the National Cancer Institute (1981)

The sensitivities of hematopoietic colony-forming cells (CFC) to N-[4-(9-acridinylamino)-3-methoxyphenyl]-methanesulfonamide (NSC-249992) (m-AMSA) were measured with an in vitro clonogenic assay, a modification of the Robinson and Pike human marrow culture system. CFC derived from bone marrow and peripheral blood of normal subjects and patients with chronic myeloid leukemia (CML) were studied. Sensitivities to m-AMSA did not differ significantly between normal marrow and blood CFC, between normal and CML CFC, or between CML CFC obtained from patients with leukemias in chronic phase and blast transformation. Drug doses and exposure times producing in vitro hematopoietic inhibition were comparable to clinically employed drug dosages and schedules associated with hematopoietic toxicity.
HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B
Authors: Michael Nassal
Journal: Gut (2015)

At least 250 million people worldwide are chronically infected with HBV, a small hepatotropic DNA virus that replicates through reverse transcription. Chronic infection greatly increases the risk for terminal liver disease. Current therapies rarely achieve a cure due to the refractory nature of an intracellular viral replication intermediate termed covalently closed circular (ccc) DNA. Upon infection, cccDNA is generated as a plasmid-like episome in the host cell nucleus from the protein-linked relaxed circular (RC) DNA genome in incoming virions. Its fundamental role is that as template for all viral RNAs, and in consequence new virions. Biosynthesis of RC-DNA by reverse transcription of the viral pregenomic RNA is now understood in considerable detail, yet conversion of RC-DNA to cccDNA is still obscure, foremostly due to the lack of feasible, cccDNA-dependent assay systems. Conceptual and recent experimental data link cccDNA formation to cellular DNA repair, which is increasingly appreciated as a critical interface between cells and viruses. Together with new in vitro HBV infection systems, based on the identification of the bile acid transporter sodium taurocholate cotransporting polypeptide as an HBV entry receptor, this offers novel opportunities to decipher, and eventually interfere with, formation of the HBV persistence reservoir. After a brief overview of the role of cccDNA in the HBV infectious cycle, this review aims to summarise current knowledge on cccDNA molecular biology, to highlight the experimental restrictions that have hitherto hampered faster progress and to discuss cccDNA as target for new, potentially curative therapies of chronic hepatitis B.
Single-agent everolimus (RAD001) in patients with relapsed or refractory multiple myeloma: Final results of a phase I study.
Authors: A. Guenther, P. Baumann, R. Burger, W. Klapper, R. Schmidmaier, M. Gramatzki
Journal: Journal of Clinical Oncology (2010)

8137 Background: The mammalian target of rapamycin (mToR) plays an important role in multiple myeloma (MM). Inhibition of mToR blocked myeloma cell growth in vitro as well as in the INA-6 preclinical xenograft model. The mToR inhibitor everolimus (RAD001) is approved for immunosuppression and recently for the treatment of renal cell cancer. Methods: In an investigator-initiated phase I/II open label trial, patients ≥ 18 years with relapsed or refractory multiple myeloma (MM) were included after at least two lines of previous treatment. The patients received a fixed dose of oral everolimus for six months following a classical dose-escalation design with three planned dose levels (5 mg, 7.5 mg and 10 mg, cohorts of 3 to 6 patients). Patients benefiting from study drug were allowed to continue on therapy. To obtain insights into the biological activity of everolimus, serum dose levels were monitored and bone marrow biopsies and aspirates were performed three times. Lymphocyte subtype analysis was performed every four weeks. Results: Seventeen patients were enrolled (13 men and 4 women, age range 52 to 76 years). The primary endpoint of this trial was safety. Since no DLT were observed the intended final daily dose of 10 mg everolimus was reached. Only 2 of 7 SAE during treatment were assessed as being possibly related to the study drug (pulmonary embolism and atypical pneumonia). Except for 2 severe thrombocytopenias no > grade 3 AE were observed during treatment. Remarkably, few infectious complications were seen despite the known immunosuppressive activity of everolimus. Anti-myeloma activity was documented in 8 out of 15 evaluable patients. One partial response in a heavily pre-treated patient and stable disease in seven additional patients (in one case lasting 9 months) were seen. The individual serum dose levels varied widely and responses seem to correlate to the dose level of everolimus achieved. Conclusions: Everolimus given orally at doses of 5 mg to 10 mg daily showed an acceptable safety profile in heavily pre-treated multiple myeloma patients. The observed responses are promising and allow to now considering further studies including combination strategies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Inflammatory Bowel Disease: Patients' Expectations in the 1990s
Authors: C S J Probert, J F Mayberry
Journal: Journal of the Royal Society of Medicine (1991)

A group of 70 patients with inflammatory bowel disease were asked to complete a questionnaire about their disease counselling preferences, 59 replied. Seventy-five per cent wanted further advice about their disease. Of these, 60% wished to receive the advice by discussion with a trained advisor. Seventy-six per cent wanted this person to be a hospital specialist, but 50% would accept advice from a specialty trained nurse. Eighty-six per cent would like this in conjunction with 'same day' telephone advice from a hospital specialist and 85% of patients wish to be taught how to adjust their own therapy. There is an increasingly important role for nurse counsellors in the management of these diseases.
Bilevel positive airway pressure in postoperative bariatric surgery
Authors: Eli Maria Pazzianotto-Forti, Letícia Baltieri, Patricia Brigatto, Carolina Moraes da Costa, Laisa Antonela dos Santos, Jessica Cristina Carbinatto, Irineu Rasera-Jr
Journal: European Respiratory Journal (2014)

Introduction: The positive pressure in the airway can contribute to the restoration of lung volumes and capacities and prevent respiratory complications arising from abdominal surgery. The aim was to investigate the use of Bilevel Positive Airway Pressure (BIPAP) in morbidly obese patients in the pre and postoperative bariatric surgery. Methods: Thirty morbidly obese individuals, aged between 25 and 55 years, admitted for bariatric surgery, underwent pulmonary function test preoperatively and on the day of discharge. After the initial assessment, the volunteers were randomly allocated in three groups. GPRE: received BIPAP treatment before surgery, for an hour, GPAR: BIPAP , immediately after surgery in the post-anesthetic recovery, for an hour and GPOST: BIPAP for one hour postoperatively (PO), on the first postoperative day. Results:There were significant reductions in slow vital capacity (SVC) and inspiratory reserve volume (IRV) in the postoperative in the three groups. The expiratory reserve volume (ERV) remained in GPRE and GPAR, while the tidal volume (TV) remained in the PO in the three groups (no significant diference). Comparing the differences between pre and postoperative, among the groups, it could be seen that the SVC showed the smallest decrease in the GPAR. Conclusions:The positive pressure supplied by BIPAP was effective in preserving the TV of morbidly obese patients in the postoperative bariatric surgery regardless of the time of application. The restoration of ERV occurs with the application of BIPAP immediately before surgery that is, in the post-anesthesia recovery, and the lowest reduction in SVC also happens when positive pressure is applied immediately after extubation.FAPESP 2013/06334-8.
Evaluation of hybridisation on oligonucleotide microarrays for analysis of drug-resistant Mycobacterium tuberculosis
Authors: D. Gryadunov, V. Mikhailovich, S. Lapa, N. Roudinskii, M. Donnikov, S. Pan'kov, O. Markova, A. Kuz'min, L. Chernousova, O. Skotnikova, A. Moroz, A. Zasedatelev, A. Mirzabekov
Journal: Clinical Microbiology and Infection (2005)
Acute Lung Injury in the Medical ICU
Authors: MARYA D. ZILBERBERG, SCOTT K. EPSTEIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The independent effects of chronic disease, age, severity of illness, lung injury score (LIS) and etiology, and preceding nonpulmonary organ-system dysfunction (OSD) on the outcome of acute lung injury (ALI) have not been examined in an exclusively medical-intensive-care-unit (MICU) population. Therefore, 107 consecutive MICU patients with ALI (76% with acute respiratory distress syndrome [ARDS]) were prospectively investigated. The impact of comorbidities, age > 65 yr, acute physiology score (APS), LIS, etiology of ALI, and OSD on hospital survival were studied. The overall mortality was 62 of 107 patients (58%), including 47 (58%) with ARDS. With univariate analysis, age > 65 yr, organ transplantation, human immunodeficiency virus (HIV) infection, active malignancy, chronic steroid use, and a septic or aspiration-related etiology of ALI were associated with a > or = 1.2-fold greater relative risk (RR) of hospital mortality. With multiple logistic regression, independent predictors of hospital death were age > 65 yr, organ transplantation, HIV infection, cirrhosis, active malignancy, and sepsis. APS, LIS, aspiration-related etiology of ALI, preceding OSD, and other comorbidities were not independently predictive of hospital death. Multivariate analysis of the ARDS cohort showed similar results, although cirrhosis and malignancy did not reach statistical significance. We conclude that comorbid conditions, older age, and sepsis etiology are independent predictors of hospital death in exclusively MICU patients with ALI (76% of whom satisfied criteria for ARDS). These factors should be considered in analyzing studies of new therapies and interpreting trends in mortality for ALI and ARDS.