tbuckley/cabot-search huggingface dataset:
Retreatment with telaprevir combination therapy in hepatitis C patients with well-characterized prior treatment response
Authors: Andrew J. Muir, Fred F. Poordad, John G. McHutchison, Mitchell L. Shiffman, Thomas Berg, Peter Ferenci, Jenny E. Heathcote, Jean-Michel Pawlotsky, Stefan Zeuzem, Henk W. Reesink, Geoffrey Dusheiko, Emily C. Martin, Shelley George, Robert S. Kauffman, Nathalie Adda
Journal: Hepatology (2011)

Retreatment with peginterferon alpha and ribavirin (PR) offers a limited chance of sustained virologic response (SVR) in patients who did not achieve SVR with prior PR treatment. This study evaluated the safety and efficacy of telaprevir-based treatment in combination with PR in well-characterized patients who did not achieve SVR in the control arms of three Phase II clinical trials. Patients eligible to enroll in this open-label nonrandomized study either met on-treatment criteria for nonresponse or relapsed after 48 weeks of treatment in the control arm of the three Phase II PROVE studies. The initial protocol was a 24-week regimen: 12 weeks of telaprevir and PR followed by an additional 12 weeks of PR. During the study the protocol was amended to extend PR to 48 weeks for patients with previous null response. All other patients with undetectable hepatitis C virus (HCV) RNA at weeks 4 and 12 received 24 weeks of therapy. Those with detectable HCV RNA at weeks 4 or 12 received a total of 48 weeks of therapy. The overall SVR rate was 59% (69/117). SVR rates with T12PR were 37% (19/51) in prior null responders, 55% (16/29) in prior partial responders, 75% (6/8) in prior breakthroughs, and 97% (28/29) in prior relapsers. The overall relapse rate was 16% (13/83). Adverse events were similar to those in previous trials with telaprevir, with 9% of patients discontinuing due to an adverse event (most commonly rash and anemia). Conclusion: This study demonstrated the benefit of retreatment with a telaprevir-based regimen for patients with well-characterized nonresponse (null and partial) or relapse to a prior course of PR treatment. (Hepatology 2011;)
Anesthesia for Outpatient Surgery
Authors: David D. Cohen
Journal: JAMA (1966)

It is possible to conduct a program of anesthesia for outpatient surgery without compromising patient safety. Intelligent selection of cases and anesthesia method minimizes the incidence of complications. The feasibility and practicality of outpatient surgery were demonstrated by the fact that only 33 of 804 patients (4.1%) were admitted as inpatients, and most of them during the early part of the study period. A properly equipped and staffed outpatient surgical unit is necessary; the availability of such a facility makes rapid expansion of surgical capabilities feasible in civil disaster. This flexibility is an attractive feature which can be helpful in obtaining funds for such expansion. An estimated $28,000 in savings to patients or insurance companies was achieved and approximately 1,000 hospital days were saved during the study period.
Finance, not learning needs, makes general practitioners attend courses: a database survey
Authors: T S Murray, L M Campbell
Journal: BMJ (1997)

Objective: To assess the medicalising effect of prescribing antibiotics for sore throat.Setting: 11 general practices in England.Design: Randomised trial of three approaches to sore throat: a 10 day prescription of antibiotics, no antibiotics, or a delayed prescription if the sore throat had not started to settle after three days.Patients: 716 patients aged 4 and over with sore throat and an abnormal physical sign: 84% had tonsillitis or pharyngitis.Outcome measures: Number and rate of patients making a first return with sore throat, pharyngitis, or tonsillitis.Early returns (within two weeks) and complications (otitis media, sinusitis, quinsy).Outcomes were documented in 675 subjects (94%).Results: Mean follow up time was similar (antibiotic group 1.07 years, other two groups 1.03 years).More of those initially prescribed antibiotics initially returned to the surgery with sore throat (38% v 27%, adjusted hazard ratio for return 1.39, 95% confidence interval 1.03 to 1.89).Antibiotics prescribed for sore throat during the previous year had an additional effect (hazard ratio 1.69, 1.20 to 2.37).Longer duration of illness ( > 5 days) was associated with increased return within six weeks (hazard ratio 2.90, 1.70 to 4.92).Prior attendance with upper respiratory conditions was also associated with increased reattendance.There was no difference between groups in early return (13/238 (5.5%) v 27/437 (6%)), or complications (2/236 (0.8%) v 3/434 (0.7%)).Conclusions: Complications and early return resulting from no or delayed prescribing of antibiotics for sore throat are rare.Both current and previous prescribing for sore throat increase reattendance.To avoid medicalising a self limiting illness doctors should avoid antibiotics or offer a delayed prescription for most patients with sore throat.
Study of DNA methylation by tobacco-specific N-nitrosamines.
Authors: A Castonguay, P G Foiles, N Trushin, S S Hecht
Journal: Environmental Health Perspectives (1985)

An enzyme-linked immunosorbent assay (BA-ELISA) involving use of biotin-labeled anti-rabbit IgG and avidin-labeled horseradish peroxidase was developed for the measurement of O6-methyl-2'-deoxyguanosine (O6-MedGuo). Up to 5 micrograms of methylated DNA was enzymatically hydrolyzed, and the extent of inhibition of binding of immobilized O6-MedGuo-bovine serum albumin to rabbit anti-O6-MedGuo was measured. Fifty percent inhibition of antigen-antibody binding was achieved with 2.5 pmole of of O6-MedGuo. Separation of O6-MedGuo from unmodified nucleosides by high-performance liquid chromatography (HPLC-BA-ELISA) allowed detection of 700 fmole O6-MedGuo in 1 mg of DNA. Among the tobacco-related carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent. In F344 rats it induces nasal cavity, lung and liver tumors. Four hours after a single IV injection of NNK to F344 rats (87 mg/kg body weight), O6-MedGuo was present in target organs (mumole O6-MedGuo/mole dGuo) (nasal mucosa, 219; lung, 13.2; and liver, 34.5) but was not detectable in nontarget organs. F344 rats receiving daily IP injections of NNK (40 mg/kg body weight) for 14 days were sacrificed 24 hr after the last injection. The levels of (O6-Medguo/dGuo) were 7.9 and 11.4 mumole/mole in the nasal mucosa and lung, respectively. In the liver no O6-MedGuo was detected, but 1050 mumole of 7-MeGua/mole Gua was measured by HPLC-fluorimetry. No DNA methylation was observed in the nasal mucosa or liver of F344 rats treated with the nicotine-derived carcinogen N'-nitrosonornicotine.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of hydrogen peroxide in the neutrophil-mediated release of prostacyclin from cultured endothelial cells.
Authors: J M Harlan, K S Callahan
Journal: Journal of Clinical Investigation (1984)

We have examined the effect of activated neutrophils on the release of prostacyclin (PGI2) from cultured endothelial cells by radioimmunoassay and thin layer chromatography of its stable metabolite, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Phorbol myristate acetate-activated neutrophils induced a time- and dose-dependent release of 6-keto-PGF1 alpha from human and bovine endothelial cell monolayers, whereas phorbol myristate acetate alone and neutrophils alone did not. Pretreatment of the endothelial cells with aspirin prevented neutrophil-mediated 6-keto-PGF1 alpha release, indicating that it did not depend upon neutrophil-generated endoperoxides. Phorbol myristate acetate-activated neutrophils from a patient with chronic granulomatous disease failed to induce endothelial 6-keto-PGF1 alpha release. Addition of catalase but not of superoxide dismutase significantly reduced human and bovine endothelial 6-keto-PGF1 alpha release by phorbol myristate acetate-activated neutrophils. Catalase-inhibitable endothelial 6-keto-PGF1 alpha release was also observed after the addition of the hydrogen peroxide-generating system, glucose-glucose oxidase, to bovine and human endothelial cell monolayers. Bovine endothelial 6-keto-PGF1 alpha release induced by exogenously generated hydrogen peroxide was attenuated by the phospholipase inhibitor mepacrine, suggesting that hydrogen peroxide may act by triggering endothelial membrane phospholipase activation. The release of 6-keto-PGF1 alpha by enzymatically or neutrophil-generated hydrogen peroxide was not associated with endothelial cell lysis as assessed by 51Cr release. We conclude that exogenously generated hydrogen peroxide or a hydrogen peroxide-derived product mediates rapid nonlytic release of PGI2 from cultured endothelial cells.
Abstract P6-07-36: A Prognostic Model For Triple-Negative Breast Cancer Patients Based On Node Status, Cathpesin-D And Ki-67
Authors: L Huang, Yb Liu, S Chen, Rj Zhou, Y Liu, Z-M Shao
Journal: Cancer Research (2012)

Abstract Background: Triple-negative breast cancer (TNBC) had been classified as a breast cancer subgroup that is negative for ER, PR and HER2. The purpose of this study was to identify prognostic factors affecting outcome in women with TNBC and to construct a prognostic model which can predict recurrence. Material and methods: We retrospectively analyzed the clinicopathologic characteristics and outcome of 284 patients diagnosed with a stage I to III triple negative breast cancer in Shanghai Cancer Hospital, including age, menopausal status, tumor size, node status, grade, ER, PR, HER-2, Cathpesin-D, PS2, Nm23, P53, Bax, Bcl-2, P27, Topo-IIa, GSTn, MDR, Cyclin D1 and Ki67. 196 patients in 2000, 2001 and 2002 belonged to training set. Prognostic significance of factors was assessed using univariate and multivariate analyses, which were combined to build a model. DFS and OS were estimated by the Kaplan-Meier method and compared among groups via the log-rank test. The prognostic value of the model was further validated in separate testing set containing 88 patients in 2003 and 2004. The median age of patients was 50 years (range, 23–85 years). 95.1% patients received cytotoxic chemotherapy after surgery; 216 (76.1%) with anthracycline based, 54 (19.0%) with CMF regimen. Results: The median follow-up duration was 70.6 months, 102 patients (35.9%) experienced recurrence or metastasis. In Cox regression, ≥4 lymph node metastasis (HR = 3.7, P &amp;lt; 0.001), Cath-D positive (HR = 2.1, p = 0.034), and Ki-67 index≥20%, (HR = 2.0, p = 0.006) were identified as independent factors for DFS, only ≥4 lymph node metastasis (HR = 4.9, P &amp;lt; 0.001) showed prognostic significance for OS. The prognostic model is based on the sum total of factors, in which ≥4+ nodes, Cath-D + or Ki-67 index≥20% would contribute 1 point separately to the risk score. According to the prognostic score, patients were assigned to low-risk group(0 and 1 point) and high-risk group(2 and 3 point). The 5-year DFS rates in two groups were 82.3% and 47.8%, respectively (p &amp;lt; 0.001). The model provided a high predictive accuracy of recurrence, which showed an AUC of 0.71 in the training set and an AUC of 0.70 in validation set. Conclusion: Based on nodal status, Ki-67 and Cathpesin-D, we built a model that had considerable clinical value in predicting recurrence in TNBC patients, which help clinicians guide the appropriate level of adjuvant treatment and scheduling of surveillance visits. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-36.
Ambulatory Surgery and the Basics of Emergency Surgical Care
Authors: Alexander N. Kingsley
Journal: JAMA (1988)

The continuing socioeconomic changes in health care have placed the burden of cost-containment on the provision side of the equation. Hospitals and physicians are under increasing pressure from governmental agencies, industry, insurance companies, and various organizations to cut down health costs but to continue to provide the same high standards of health care to which this country has become accustomed and expects. The provision of health care on an outpatient basis is expanding rapidly. It is estimated that about 20% to 40% of all procedures are now done in the ambulatory setting. Ironically, ambulatory surgery was the oldest form of surgery performed by itinerant surgeons before the advent of organized hospitals. Since the publication in 1942 of the first edition of<i>Surgery of the Ambulatory Patient</i>, by L. K. Ferguson, the work has become the classic text in its field. Now, 46 years later, the seventh edition has proved itself
Diminazene Attenuates Pulmonary Hypertension and Improves Angiogenic Progenitor Cell Functions in Experimental Models
Authors: Vinayak Shenoy, Altin Gjymishka, Yagna P. Jarajapu, Yanfei Qi, Aqeela Afzal, Katya Rigatto, Anderson J. Ferreira, Rodrigo A. Fraga-Silva, Patrick Kearns, Jane Yellowlees Douglas, Deepmala Agarwal, Kamal K. Mubarak, Chastity Bradford, William R. Kennedy, Joo Y. Jun, Anandharajan Rathinasabapathy, Erin Bruce, Dipankar Gupta, Arturo J. Cardounel, J. Mocco, Jawaharlal M. Patel, Joseph Francis, Maria B. Grant, Michael J. Katovich, Mohan K. Raizada
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Studies have demonstrated that angiotensin-converting enzyme 2 (ACE2) plays a protective role against lung diseases, including pulmonary hypertension (PH). Recently, an antitrypanosomal drug, diminazene aceturate (DIZE), was shown to exert an "off-target" effect of enhancing the enzymatic activity of ACE2 in vitro.To evaluate the pharmacological actions of DIZE in experimental models of PH.PH was induced in male Sprague Dawley rats by monocrotaline, hypoxia, or bleomycin challenge. Subsets of animals were simultaneously treated with DIZE. In a separate set of experiments, DIZE was administered after 3 weeks of PH induction to determine whether the drug could reverse PH.DIZE treatment significantly prevented the development of PH in all of the animal models studied. The protective effects were associated with an increase in the vasoprotective axis of the lung renin-angiotensin system, decreased inflammatory cytokines, improved pulmonary vasoreactivity, and enhanced cardiac function. These beneficial effects were abolished by C-16, an ACE2 inhibitor. Initiation of DIZE treatment after the induction of PH arrested disease progression. Endothelial dysfunction represents a hallmark of PH pathophysiology, and growing evidence suggests that bone marrow-derived angiogenic progenitor cells contribute to endothelial homeostasis. We observed that angiogenic progenitor cells derived from the bone marrow of monocrotaline-challenged rats were dysfunctional and were repaired by DIZE treatment. Likewise, angiogenic progenitor cells isolated from patients with PH exhibited diminished migratory capacity toward the key chemoattractant stromal-derived factor 1α, which was corrected by in vitro DIZE treatment.Our results identify a therapeutic potential of DIZE in PH therapy.
Imaging the Unfolded Protein Response in Primary Tumors Reveals Microenvironments with Metabolic Variations that Predict Tumor Growth
Authors: Michael T. Spiotto, Alice Banh, Ioanna Papandreou, Hongbin Cao, Michael G. Galvez, Geoffrey C. Gurtner, Nicholas C. Denko, Quynh Thu Le, Albert C. Koong
Journal: Cancer Research (2009)

Cancer cells exist in harsh microenvironments that are governed by various factors, including hypoxia and nutrient deprivation. These microenvironmental stressors activate signaling pathways that affect cancer cell survival. While others have previously measured microenvironmental stressors in tumors, it remains difficult to detect the real-time activation of these downstream signaling pathways in primary tumors. In this study, we developed transgenic mice expressing an X-box binding protein 1 (XBP1)-luciferase construct that served as a reporter for endoplasmic reticulum (ER) stress and as a downstream response for the tumor microenvironment. Primary mammary tumors arising in these mice exhibited luciferase activity in vivo. Multiple tumors arising in the same mouse had distinct XBP1-luciferase signatures, reflecting either higher or lower levels of ER stress. Furthermore, variations in ER stress reflected metabolic and hypoxic differences between tumors. Finally, XBP1-luciferase activity correlated with tumor growth rates. Visualizing distinct signaling pathways in primary tumors reveals unique tumor microenvironments with distinct metabolic signatures that can predict for tumor growth.
Analysis of the bioactive components from different growth stages of Fritillaria taipaiensis P. Y. Li
Authors: Rui Peng, Peng Ma, Rangyu Mo, Nianxi Sun
Journal: Acta Pharmaceutica Sinica B (2013)

High-performance liquid chromatography (HPLC) coupled with an evaporative light scattering detector (ELSD) or a diode array detector (DAD) were utilized for the quantitative analysis of 4 alkaloids (peimisine, sipeimine, peimine and peiminine) and 9 nucleosides and nucleobases (uracil, uridine, adenosine, adenine, inosine, thymine, cytidine, guanosine and thymidine) from Fritillaria taipaiensis P. Y. Li that had been cultivated in the same field for 2–6 years. The content of peimisine, sipeimine, peimine, peiminine, uracil, thymine, adenine and inosine in plants cultivated for 2–4 years was significantly higher than that of plants cultivated for 5–6 years, while the content of cytidine, uridine, guanosine, thymidine and adenosine did not change over this period. This is the first evaluation of variation in the bioactive compounds in F. taipaiensis over its life cycle.
Psychotropic drugs and road accidents.
Authors: R P Snaith, I Hindmarch, V F Standing
Journal: BMJ (1977)

Two dietary factors have been implicated in the parallel aging of tendons and arteries.Schwartz2 suggests that the trace element silicon is the factor in dietary fibre and hard water which reduces the incidence of CHD.Silicon contributes to the stability of connective tissue by forming -O-Si-O-bridges.Ascorbic acid is the second factor.Its role in collagen synthesis-' makes it essential for both tendons and arteries.Our observations on cardiac patients who take up marathon running show a conspicuous increase in silicon-rich foodstuffs (pectin, bran, and alfalfa) and also ascorbic acid (fresh fruit and vitamin C supplements).The longest run for cardiac patients is the Primo 100-km run on the island of Oahu.It is supported by the cardiac rehabilitation programme of the Honolulu YMCA.The event is social and non-competitive.In our view any dietary manipulation should be aimed at increasing "distance covered on foot.
Effects of low dose fluticasone/salmeterol combination on surrogate inflammatory markers in moderate persistent asthma
Authors: G. P. Currie, N. J. Syme‐Grant, L. C. McFarlane, F. A. Carey, B. J. Lipworth
Journal: Allergy (2003)

Background: Noninvasive surrogate markers provide valuable information on the asthmatic inflammatory process. We wished to examine the effects of low dose fluticasone/salmeterol combination on different commonly used inflammatory markers in moderate persistent asthma. Methods: Twenty‐five moderate persistent atopic asthmatics were enrolled of whom 20 completed an open label study. Following an initial 4 week steroid washout period in which patients took salmeterol 50 μ g dry powder inhaler 1 puff BD, they received the addition of fluticasone as fluticasone 100 μ g/salmeterol 50 μ g combination dry powder inhaler 1 puff BD for the next 2 weeks. Exhaled nitric oxide, spirometry, methacholine PD 20 , sputum/blood eosinophils and sputum/serum eosinophil cationic protein (ECP) were measured following the salmeterol only and fluticasone/salmeterol combination treatment periods. Results: Compared to salmeterol alone (i.e. after the steroid washout), the use of fluticasone/salmeterol combination conferred significant improvements ( P &lt; 0.05) in all surrogate markers of inflammation apart from serum ECP. Geometric mean fold changes were 4.3‐fold/1.3‐fold for sputum/blood eosinophils, 2.2‐fold/1.2‐fold for sputum/serum ECP, 2.3‐fold for methacholine PD 20 and 1.8‐fold for exhaled nitric oxide. Conclusions: Surrogate markers apart from serum ECP may be used as a guide to evaluate the anti‐inflammatory effects of low dose inhaled corticosteroids. Sputum markers tend to be more sensitive than blood when assessing the anti‐inflammatory response.
Study Of Sublingual Immunotherapy In Subjects With Dermatophagoides Farniae And Timothy Grass Allergy
Authors: N.R. Reshamwala, S.J. Song, G.P. Yu, R. Swamy, S.W. Berquist, T. Nguyen, E.G. Hoyt, S. Vissamsetti, A.M. Sivagnanasundaram, V.E. Saper
Journal: Journal of Allergy and Clinical Immunology (2009)
Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases
Authors: Chae Hwa Yoo, Hee-Jun Na, Dong-Seol Lee, Soon Chul Heo, Yuri An, Junghwa Cha, Chulhee Choi, Jae Ho Kim, Joo-Cheol Park, Yee Sook Cho
Journal: Biomaterials (2013)
Update on actinic keratosis and Bowen's disease in clinical trial experience
Authors: S.J. Salasche
Journal: British Journal of Dermatology (2003)

Journal Article Update on actinic keratosis and Bowen's disease in clinical trial experience Get access S.J. Salasche S.J. Salasche Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue s66, 1 November 2003, Page 30, https://doi.org/10.1046/j.0366-077X.2003.5686a.x Published: 01 November 2003
Abnormal proliferation of CD4? CD8+ ??+ T cells with chromosome 6 anomaly: Role of fas ligand expression in spontaneous regression of the cells
Authors: Naoaki Ichikawa, Kiyoshi Kitano, Toshiro Ito, Takayuki Nakazawa, Shigetaka Shimodaira, Fumihiro Ishida, Kendo Kiyosawa
Journal: American Journal of Hematology (1999)

We report a case of granular lymphocyte proliferative disorder accompanied with hemolytic anemia and neutropenia. Phenotypes of the cells were T cell receptor gammadelta+ CD3+ CD4- CD8+ CD16+ CD56- CD57-. Southern blot analysis of T cell receptor beta and gamma chains demonstrated rearranged bands in both. Chromosomal analysis after IL-2 stimulation showed deletion of chromosome 6. Sorted gammadelta+ T cells showed an increase in Fas ligand expression compared with the levels in sorted alphabeta+ T cells. The expression of Fas ligand on these gammadelta+ T cells increased after IL-2 stimulation. The patient's anemia improved along with a decrease in granular lymphocyte count and disappearance of the abnormal karyotype without treatment. The expression of Fas ligand may be involved in spontaneous regression of granular lymphocyte proliferation with hemolytic anemia.