tbuckley/cabot-search huggingface dataset:
Cisplatin, Etoposide, and Paclitaxel in the Treatment of Patients With Extensive Small-Cell Lung Carcinoma
Authors: Bonnie S. Glisson, Jonathan M. Kurie, Roman Perez-Soler, Nikolous J. Fox, William K. Murphy, Frank V. Fossella, Jin S. Lee, Michael B. Ross, David A. Nyberg, Katherine M.W. Pisters, Dong M. Shin, Waun Ki Hong
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The combination of cisplatin, etoposide, and paclitaxel was studied in patients with extensive small-cell lung cancer in a phase I component followed by a phase II trial to determine the maximum-tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates. PATIENTS AND METHODS: Forty-one patients were treated between October 1993 and April 1997. Doses for the initial cohort were cisplatin 75 mg/m 2 on day 1, etoposide 80 mg/m 2 /d on days 1 to 3, and paclitaxel 130 mg/m 2 on day 1 over 3 hours. Cycles were repeated every 3 weeks for up to six cycles. The MTD was reached in the first six patients. In these six patients and in the next 35 patients, who were entered onto the phase II trial, response and survival were estimated. RESULTS: At the initial dose level, one of six patients developed febrile neutropenia, and five of six achieved targeted neutropenia (nadir absolute granulocyte count, 100 to 1,000/μL) without any other dose-limiting toxicity, defining this level as the MTD. Grade 4 neutropenia was observed in 88 (47%) of 188 total courses administered at or less than the MTD. Neutropenia was associated with fever in only 17 (9%) of 188 courses, but two patients experienced neutropenic sepsis that was fatal. Nonhematologic toxicity greater than grade 2 was observed in 10 (5%) of 188 total courses, with fatigue, peripheral neuropathy, and nausea/vomiting most common. The overall objective response rate was 90% of 38 assessable patients: six complete responses (16%) and 28 partial responses(74%). Median progression-free and overall survival durations were 31 and 47 weeks, respectively. CONCLUSION: The combination of cisplatin, etoposide, and paclitaxel produced response and survival rates similar to those of other combinations and was well tolerated.
Clinical findings and respiratory function in infants following repair of oesophageal atresia and tracheo-oesophageal fistula
Authors: CS Beardsmore, UM MacFadyen, MS Johnstone, A Williams, H Simpson
Journal: European Respiratory Journal (1994)

Survival rates for infants undergoing surgical repair of oesophageal atresia with tracheo-oesophageal fistula (OA-TOF) have improved dramatically, but this condition remains associated with substantial morbidity. Most studies of patients following OA-TOF repair have concentrated on school-age and older people; whereas, the most hazardous period is infancy. We aimed to assess respiratory function in a group of infants following primary operative repair, and to relate the results to clinical findings during the first year of life. We studied 16 infants within 3 months of primary repair of OA-TOF. Measurements were made of maximum expiratory flow at functional residual capacity (VmaxFRC), thoracic gas volume (TGV) and airways resistance (Raw). Ten infants had tests repeated, usually to assess progress alongside continuing symptoms, or to ascertain improvement following additional surgery. Seven infants had essentially normal initial respiratory function tests, and six remained either symptom-free or developed only minor clinical problems. One infant subsequently developed stridor, with spontaneous improvement towards the end of the first year. The remaining nine infants had abnormal initial respiratory function tests: one was symptom-free at that time. The remainder developed respiratory and/or gastro-oesophageal symptoms. The functional abnormalities appeared to reflect the severity of the clinical problems encountered. We conclude that respiratory function testing in infants following OA-TOF repair may augment the value of clinical appraisal, help define postoperative respiratory status, and provide a general guide to likely clinical progress.
Myeloid Suppressor Cells Accumulate and Regulate Blood Pressure in Hypertension
Authors: Kandarp H. Shah, Peng Shi, Jorge F. Giani, Tea Janjulia, Ellen A. Bernstein, You Li, Tuantuan Zhao, David G. Harrison, Kenneth E. Bernstein, Xiao Z. Shen
Journal: Circulation Research (2015)

Chronic inflammation is a major contributor to the progressive pathology of hypertension, and T-cell activation is required for the genesis of hypertension. However, the precise role of myeloid cells in this process is unclear.To characterize and understand the role of peripheral myeloid cells in the development of hypertension.We examined myeloid cells in the periphery of hypertensive mice and found that increased numbers of CD11b(+)Gr1(+) myeloid cells in blood and the spleen are a characteristic of 3 murine models of experimental hypertension (angiotensin II, L-NG-nitroarginine methyl ester, and high salt). These cells express surface markers and transcription factors associated with immaturity and immunosuppression. Also, they produce hydrogen peroxide to suppress T-cell activation. These are characteristics of myeloid-derived suppressor cells (MDSCs). Depletion of hypertensive MDSCs increased blood pressure and renal inflammation. In contrast, adoptive transfer of wild-type MDSCs to hypertensive mice reduced blood pressure, whereas the transfer of nicotinamide adenine dinucleotide phosphate oxidase 2-deficient MDSCs did not.The accumulation of MDSCs is a characteristic of experimental models of hypertension. MDSCs limit inflammation and the increase of blood pressure through the production of hydrogen peroxide.
Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer.
Authors: M J Moore, D Osoba, K Murphy, I F Tannock, A Armitage, B Findlay, C Coppin, A Neville, P Venner, J Wilson
Journal: Journal of Clinical Oncology (1994)

PURPOSE This phase II study was designed to assess the effects of mitoxantrone with prednisone in patients with metastatic prostate cancer who had progressed on hormonal therapy. The methods of assessment included quality-of-life analyses, pain indices, analgesic scores, and the National Prostatic Cancer Project (NPCP) criteria. PATIENTS AND METHODS Patients received mitoxantrone 12 mg/m2 intravenously every 3 weeks plus prednisone 10 mg orally daily. All had a castrate serum testosterone and Eastern Cooperation Oncology Group (ECOG) performance status &lt; or = 3, and had not received prior chemotherapy. Every 3 weeks, analgesic intake was scored, and a present pain intensity (PPI) record and visual analog scale (VAS) describing pain were collected. Every 6 weeks, the European Organization for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire plus a prostate-specific module were completed. A palliative response was defined as a decrease in analgesic score by &gt; or = 50% or a decrease in PPI by &gt; or = two integers without any increase in the other. RESULTS Twenty-seven patients were entered onto the study. Nine of 25 (36%) assessable patients achieved a palliative response maintained for &gt; or = two cycles (range, two to eight or more). Improvements in mean PPI and VAS pain scores after each cycle of therapy (P &lt; .05) were seen. Quality-of-life analysis showed improvements in social and emotional functioning, and in pain and anorexia. Using NPCP criteria, one patient achieved a partial response (PR) and 12 had stable disease; one of seven patients with measurable disease had a PR. No serious nonhematologic toxicity was experienced, and there were no episodes of febrile neutropenia. CONCLUSION Mitoxantrone with low-dose prednisone is a well-tolerated treatment regimen that has some beneficial effects on disease-related symptoms and quality of life for patients with advanced prostate cancer.
Influence of gender on thoracoabdominal volumes and inspiratory muscular activity during quiet and deep breathings: A cross-sectional study
Authors: Denise Paisani, Desiderio Cano, Adriana Lunardi, Cibele Marques da Silva, Celso Carvalho
Journal: European Respiratory Journal (2013)

Differences between gender on resting pulmonary volumes and inspiratory muscular activity during quiet and deep breathings remains unknown. Objective: To investigate the influence of gender on thoracoabdominal volumes and inspiratory muscular activity analyzed concurrently during quiet and deep breathings. Methods: 136 subjects with normal lung function: 55 males (61±13 yrs, 25.2±4.6 Kg/m2) and 81 females (55±15 yrs, 25.0±5.1 Kg/m2) performed quiet followed by deep breaths. Total Chest wall (VCW), upper (VURC) and lower ribcage (VLRC) and abdominal (VABD) compartmental volumes were quantified by optoelectronic plethysmography (OEP) concurrently with sternocleidomastoid (SCM), upper (UIC) and lower intercostals (LIC) activity quantified by surface electromyography. One way repeated measures ANOVA with post hoc Student Newman-Keuls were used and significance level was set at 5%. Results: During deep breathing all volumes, except VLRC, were greater in males than in females (VCW=1,845±426 mL vs. 1,313±350 mL, VPRC=563±206mL vs. 481±203mL, VABD=886±306mL vs. 466±197mL, p<0.001). In contrary, inspiratory muscular activity was higher in females than in males in LIC (11.0±8.5µV vs. 8.2±5.1µV, p<0.05) and SCM (23.9±25.0µV vs. 17.3±12.6µV, p<0.01). No differences were observed during quiet breathing. Conclusion: Males breathes greater thoracoabdominal volumes; however, deep breaths require higher inspiratory muscular activity by females.
Online selfmanagement in patients with COPD or asthma: With or without the healthcare provider?
Authors: Johannes In 't Veen, Bianka Mennema, Esther van Noort
Journal: European Respiratory Journal (2012)

Introduction   Selfmanagement plays a key role in integrated care strategies for chronic diseases. Curavista Health is an online patient self-management platform for several chronic diseases, including asthma and COPD: MyCOPDonline & Myasthmaonline which consists of 3 basic-elements:  1. Health status; 2. Self management; 3. eConsult.  We incorporated the program into our daily hospital routine for outpatients. Patients however also can participate without health care provider, as open acces program.   Aim   The aim of the study was to retrospectively analyze the adherence to the program of patients with or without health care provider.   Results   The content of the program was identical in both groups. Age and gender were comparable. In the group without coaching (n=831), 68% used the program once, 18% twice and 14% three times or more. In the group with coaching (n=95), 33% used the program once, 17% twice and 50% three times or more (p   Discussion.    “Self-management” suggests that patients manage themselves and the role of the professional is limited. In contrast, these data suggest that participants make better use of eHealth programmes when supported by healthcare professionals. Therefore eHealth should be embedded into regular care. It might imply not only a role change for patients to achieve self management, but also for the health care professional in transition from medication manager to coach.
Meticillin-resistant Staphylococcus aureus CC398 is an increasing cause of disease in people with no livestock contact in Denmark, 1999 to 2011
Authors: Jesper Larsen, Andreas Petersen, Marit Sørum, Marc Stegger, Lieke van Alphen, Palle Valentiner-Branth, Lisbet Krause Knudsen, Lars Stehr Larsen, Beth Feingold, Lance Bradley Price, Paal Skytt Andersen, Anders Rhod Larsen, Robert Leo Skov
Journal: Eurosurveillance (2015)

Livestock constitutes a potential reservoir of meticillin-resistant Staphylococcus aureus isolates belonging to a recently derived lineage within clonal complex 398 (MRSA CC398-IIa). Since its discovery in the early 2000s, this lineage has become a major cause of human disease in Europe, posing a serious public health challenge in countries with intensive livestock production. To retrace the history of human colonisation and infection with MRSA CC398-IIa in Denmark, we conducted a nationwide, retrospective study of MRSA isolates collected from 1999 to 2011. Among 7,429 MRSA isolates screened, we identified 416 MRSA CC398-IIa isolates. Of these, 148 were from people with infections, including 51 from patients reporting no livestock exposure. The first cases of MRSA CC398-IIa infection in Denmark occurred in 2004. Subsequently, the incidence of MRSA CC398-IIa infection showed a linear annual increase of 66% from 2004 to 2011 (from 0.09 to 1.1 per 100,000 person-years). There were clear temporal and spatial relationships between MRSA CC398-IIa-infected patients with and without livestock exposure. These findings suggest substantial dissemination of MRSA CC398-IIa from livestock or livestock workers into the Danish community and underscore the need for strategies to control its spread both on and off the farm.
Abstract 12041: The Risk of Peri-Operative Bleeding with Warfarin Compared to Two Doses of Dabigatran: Results From the RE-LY Trial
Authors: Jeff S Healey, John Eikelboom, Lars Wallentin, jonas Oldgren, James Douketis, Stuart J Connolly, Salim Yusuf, Michael D Ezekowitz
Journal: Circulation (2011)

Background: The RE-LY trial demonstrated that Dabigatran (Dab) has advantages over warfarin in patients with atrial fibrillation. However; the risk of peri-operative bleeding has not been establish...
Early detection of undiagnosed COPD in general practice; the yield of population-based screening according to socioeconomic status
Authors: Joseph Dirven, Huibert Tange, Jean Muris, Onno van Schayck
Journal: European Respiratory Journal (2013)

Background.  The burden of chronic obstructive pulmonary disease (COPD) is high. Health benefits can be gained in primary care by early detection and preventive measures.   Aim.  To determine the effectiveness of a population-based screening procedure including a risk questionnaire and spirometry testing. To compare two strategies of providing this procedure in different socioeconomic settings.   Method.  A cluster-randomised controlled trial among all 40-70 years of age in 16 family practices. Practices were randomized on strategy and stratified on socioeconomic profile. The Respiratory Health Screening Questionnaire (RHSQ) was used. In the practice managed condition, the practice was responsible for the whole procedure. In the patient managed condition patients were responsible for calculating their RHSQ risk score and applying for a spirometry test. Main outcome measure was the rate of COPD diagnoses after screening.   Results.  In the practice-managed condition more new COPD patients were detected (36%) than in the patient-managed condition (18%). In low-SES practices more high-risk patients were found (16%) than in average-SES practices (9%). Recalculated for a standard Dutch practice (2250 patients) the yield would be 20% increase of known cases.   Conclusion.  The practice-managed variant of this screening procedure shows a substantial yield of new COPD diagnoses for both low-SES and average-SES practices.
DSM-III psychiatric disorders among Hmong refugees in the United States: a point prevalence study
Authors: J Westermeyer
Journal: American Journal of Psychiatry (1988)

The author reports on a survey of 97 Hmong adult refugees in the United States. Thirty of these refugees showed symptoms of chronic maladjustment, and 13 showed another DSM-III axis I disorder; two manifested a paranoid psychosis, and six had a major depression. There were few axis II diagnoses. Medical conditions were frequent and often psychophysiological in nature, but they were not associated with axis I disorders. Axis IV psychosocial stressors were not associated with axis I diagnoses, but subjects with an axis I disorder tended to show lower adaptive levels on axis V. The demographic condition most strongly associated with an axis I diagnosis was current status as a welfare recipient.
Psychological Factors Influence the Success of Coronary Artery Surgery
Authors: K S Channer, S O'Connor, S Britton, D Walbridge, J Russell Rees
Journal: Journal of the Royal Society of Medicine (1988)

Thirty-six patients with angina were investigated by treadmill exercise testing and coronary angiography prior to coronary artery surgery. Severity of angina was judged by interview and self-assessment visual analogue scale and all patients were psychiatrically assessed. Further physical and psychiatric assessments were made at 3 and 6 months postoperatively. Eleven patients (31%) had significant psychiatric morbidity preoperatively and these had worse symptom scores and exercise tolerance compared with non-psychiatric cases, despite equivalent coronary angiographic findings and left ventricular function. Post-operatively, exercise tolerance improved equally in both groups but psychiatric cases remained significantly more symptomatic. Psychiatric morbidity remained unchanged throughout the study. We conclude that almost one third of patients with severe angina have psychiatric morbidity which is associated with a poor symptomatic response to coronary artery surgery, despite objective improvement in exercise tolerance. Ways of improving the symptomatic response to surgery in patients with coexisting psychiatric morbidity should be studied.
Effect of thrombin inhalation in a murine model of bronchial asthma
Authors: Takehiro Takagi, Masahiro Onishi, Masahiro Naito, Atsushi Fujiwara, Tetsu Kobayashi, Hiroyasu Kobayashi, Corina D'Alessandro-Gabazza, Esteban Gabazza, Osamu Taguchi
Journal: European Respiratory Journal (2011)

Background: Thrombin is the effector enzyme of the coagulation system with important biological functions not only in thrombosis and hemostasis but also in inflammation. The precise role of thrombin in allergy remains unknown but recently there are some reports showing that thrombin plays an important role in the pathogenesis of asthma. In addition, previously we reported that thrombin inhibitor did not improve allergic response in murine asthma model.  Objectives: To evaluate the effect of inhaled thrombin on airway inflammation and hyperresponsiveness in a murine asthma model.  Methods: Bronchial asthma was induced by sensitization and challenge with ovalbumin (OVA). Littermates treated with saline were used as controls. The effect of inhaled different dose of thrombin was assessed by administering prior to OVA exposure. Airway inflammation was evaluated by measuring the number of inflammatory cells and the level of cytokine in bronchoalveolar lavage fluid (BAL). Airway hyperresponsiveness was measured using a plethysmograph.  Results: The levels of IgE, IL-5, and the number of eosinophils in BAL were decreased in low dose of thrombin treated mice compared to saline treated mice. The degree of airway hyperresponsiveness was significantly decreased in low dose of thrombin treated mice as compared to saline treated mice.  Conclusion: These results suggest thrombin exerts a differential effect in bronchial asthma depending on its concentration.
Quality of life and symptoms improvement after 6 months treatment with roflumilast 500 μg daily in a large Greek COPD cohort
Authors: Nikolaos Tzanakis, Alexandros Ginis, Grigoris Politis, Grigoris Kaltsas, Artemis Nomikou, Nikolaos Spandideas, Nikolaos M. Siafakas
Journal: European Respiratory Journal (2013)

Background and aims   We evaluated the changes in MRC dyspnea index and CCQ questionnaire in Greek COPD patients treated with Roflumilast during a 6 month cohort study (ATLAS study).   Materials and Methods   Changes in CCQ questionnaire and MRC dyspnea score were evaluated in 2167 patients with severe chronic obstructive pulmonary disease (COPD), FEV1 (% pred) 49.1± 14.7 aged 70.5 ± 9.7 with a mean Body Mass Index of 29.1±4.8 (mean values) following treatment with Roflumilast for a six month observational period. Data were collected at baseline (V0), 3 rd  (V1) and 6 th  month (V2). Spirometric evaluation, (FEV1, FVC, FEV/FVC) and body weight measurement were also included.   Results   Total CCQ questionnaire demonstrated clinically relevant and statistically significant improvement between pre and 6-months post-treatment period (x±SD) Δ=-1.53±1.07, p Conclusion : Six-months treatment with roflumilast 500 μg daily of naive to roflumilast large COPD cohort, showed significant and clinically meaningful early improvement in their MRC dyspnea index and their quality of life.
Spontaneous pregnancy in a woman with lupus and thyroiditis despite imminent premature ovarian failure
Authors: D Le Thi Huong
Journal: Annals of the Rheumatic Diseases (2003)

<h3>Abstract</h3> Understanding the finely orchestrated interactions leading to or preventing programmed cell death (apoptosis) is of utmost importance in cancer research since the failure of these systems could eventually lead to the onset of the disease. In this regard, the maintenance of a delicate balance between promoters and inhibitors of mitochondrial apoptosis is crucial, as demonstrated by the interplay among the Bcl-2 family members. Particularly, Bcl-x<sub>L</sub> is a target of interest due to its forefront role of its dysfunctions in cancer development. Bcl-x<sub>L</sub> prevents apoptosis by binding both the pro-apoptotic BH3-only proteins, as PUMA, and noncanonical partners such as p53 at different sites. An allosteric communication between the BH3-only proteins binding pocket and the p53 binding site has been postulated and supported by NMR and other biophysical data, mediating the release of p53 from Bcl-x<sub>L</sub> upon PUMA binding. The molecular details, especially at the residue level, of this mechanism remain unclear. In this work, we investigated the distal communication between these two sites in both Bcl-x<sub>L</sub> in its free state and bound to PUMA, and we evaluated how missense mutations of Bcl-x<sub>L</sub> found in cancer samples might impair the communication and thus the allosteric mechanism. We employed all-atom explicit solvent microsecond molecular dynamics simulations analyzed through a Protein Structure Network approach and integrated with calculations of changes in free energies upon cancer-related mutations identified by genomics studies. We found a subset of candidate residues responsible for both maintaining protein stability and for conveying structural information between the two binding sites and hypothesized possible communication routes between specific residues at both sites.
Allergic diseases and the effect of inhaled epinephrine in children with acute bronchiolitis: follow-up from the randomised, controlled, double-blind, Bronchiolitis ALL trial
Authors: Håvard Ove Skjerven, Leif Bjarte Rolfsjord, Teresa Løvold Berents, Hanne Engen, Edin Dizdarevic, Cathrine Midgaard, Bente Kvenshagen, Marianne Hanneborg Aas, Jon Olav Gjengstø Hunderi, Karen Eline Stensby Bains, Petter Mowinckel, Kai-Håkon Carlsen, Karin C Lødrup Carlsen
Journal: The Lancet Respiratory Medicine (2015)