tbuckley/cabot-search huggingface dataset:
Neoadjuvant Chemotherapy in Stage III NSCLC
Authors: Jeffrey Allen, Mohammad Jahanzeb
Journal: Journal of the National Comprehensive Cancer Network (2008)

Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related mortality in the United States. Current standard care for treating NSCLC is surgical resection, when feasible, followed by adjuvant chemotherapy in stages II and III. Neoadjuvant or induction chemotherapy may have several potential advantages compared with adjuvant chemotherapy and has been evaluated in randomized and nonrandomized clinical trials in NSCLC. This article reviews the data for neoadjuvant chemotherapy in NSCLC with a particular focus on regionally advanced disease (stage III) that is still amenable to surgical resection.
The imperative to invest in science has never been greater
Authors: John M. Carethers, Shaun Coughlin, Betty Diamond, Serpil Erzurum, Linda P. Fried, J. Larry Jameson, Kenneth Kaushansky, Mary E. Klotman, Stanley Lemon, Beverly Mitchell, Paul Rothman, Charles Sawyers, Christine Seidman, Stefan Somlo
Journal: Journal of Clinical Investigation (2014)

In order to sustain and improve the health of Americans, to ensure our ability to overcome new health challenges, and to realize the economic benefits of a vigorous scientific economy, we encourage our government to implement three actions. First, establish predictable, managed growth in the US scientific enterprise by establishing a sustainable and predictable real annual increase in science funding. This will require additional investments in the proven NIH-university partnership to maintain our world-leading position in biomedical science. Second, preserve the current cadre of well-trained junior scientists, including physician-scientists, and maintain a pipeline of young scientists motivated to innovate and improve health. Third, analyze changing health needs and priorities for health science–related investments in order to address ongoing shifts in population demographics and diseases, opportunities for improved prevention or treatment, and the availability of new scientific tools and disciplines.
A phase II study of docetaxel in patients with paclitaxel-resistant metastatic breast cancer.
Authors: V Valero, S E Jones, D D Von Hoff, D J Booser, R G Mennel, P M Ravdin, F A Holmes, Z Rahman, M W Schottstaedt, J K Erban, L Esparza-Guerra, R H Earhart, G N Hortobagyi, H A Burris
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the efficacy and safety of docetaxel in patients with paclitaxel-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS Docetaxel (100 mg/m2) was administered every 3 weeks to 46 patients registered at four centers. Patients had previously received &lt; or = two chemotherapy regimens for MBC. All patients had progressive disease while receiving paclitaxel therapy. Treatment was repeated until there was evidence of disease progression or for a maximum of three cycles after best response. RESULTS Objective responses were seen in eight of 44 assessable patients (18.1%; 95% confidence interval [CI], 6.7% to 29.5%). Seven patients had partial responses and one patient responded completely. Response rates were not significantly different by previously received paclitaxel dose or resistance. No responses were seen in 12 patients who had previously received paclitaxel by 24-hour infusion, but the response rate in 32 patients who had received paclitaxel by 1- to 3-hour infusion was 25%. The median response duration was 29 weeks and the median time to disease progression was 10 weeks. Median survival was 10.5 months. Clinically significant (severe) adverse events included neutropenic fever (24% of patients), asthenia (22%), infection (13%), stomatitis (9%), neurosensory changes (7%), myalgia (7%), and diarrhea (7%). CONCLUSION Docetaxel is active in patients with paclitaxel-resistant breast cancer, particularly in those who failed to respond to brief infusions of paclitaxel. Response rates were comparable to or better than those seen with other therapies for patients with paclitaxel-resistant MBC. This confirms preclinical studies, which indicated only partial cross-resistance between paclitaxel and docetaxel.
Injuries in women's professional soccer * Commentary
Authors: E Giza, K Mithöfer, L Farrell, B Zarins, T Gill
Journal: British Journal of Sports Medicine (2005)

The injury data from the first two seasons of the Women's United Soccer Association (WUSA) were analysed to determine the injury incidence, anatomic location of injuries, and relation of player position.Injury data on 202 players from eight teams during the first two seasons of the WUSA were prospectively collected and analysed.A total of 173 injuries occurred in 110 players with an overall injury incidence rate of 1.93 injuries per 1000 player hours. The incidence of injury during practice and games was 1.17 and 12.63 per 1000 player hours, respectively. Of the injuries 82% were acute and 16% were chronic. Most of the injuries (60%) were located in the lower extremities. Strains (30.7%), sprains (19.1%), contusions (16.2%), and fractures (11.6%) were the most common diagnoses and the knee (31.8%) and head (10.9%) were the most common sites of injury. Anterior cruciate ligament (ACL) injuries accounted for 4.6% of all injuries and the incidence of ACL tears was 0.09 per 1000 player hours (practice 0.04, game 0.90). Midfielders suffered the most injuries (p<0.007).We conclude that the injury incidence in the WUSA is lower than the 6.2 injuries per 1000 player hours found in the corresponding male professional league (Major League Soccer); however, knee injuries predominate even in these elite female athletes.
Noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during induction of anesthesia of newborn with bowel atresia
Authors: Ievgenii Vzhetson, Dmytro Dmytriiev, Konstantin Bertsun, Nataliia Kosechenko
Journal: European Respiratory Journal (2013)

Background: The aim of this prospective study was to determine whether noninvasive positive pressure ventilation (NPPV) improves arterial oxygenation and end-expiratory lung volume (EELV) compared with conventional preoxygenation, and whether NPPV followed by early recruitment maneuver (RM) after endotracheal intubation (ETI) further improves oxygenation and respiratory function compared with NPPV alone.

Methods: 28 patients were randomized to receive 5 min of either conventional preoxygenation with spontaneous breathing of 100% O2 (CON), NPPV, or NPPV followed by RM (NPPV+RM). Gas exchange was measured in awake patients, at the end of preoxygenation, after ETI, and 5 min after the onset of mechanical ventilation(MV). EELV was measured after ETI and 5 min after MV. The primary endpoint was arterial oxygenation 5 min after the onset of MV. Results are presented as mean±SD.

Results: At the end of preoxygenation, Pao2 was higher in the NPPV and NPPV+RM groups (376±72 mmHg and 369±80 mmHg, P<0.001) compared with the CON group (295±56 mmHg) and remained higher after ETI (232 ±92 mmHg and 218±104 mmHg, in the NPPV and NPPV+RM groups, P<0.01 compared with the CON group [146±52 mmHg]). After ETI, EELV was higher in the NPPV group compared with the CON group (P<0.001). Compared with NPPV alone, RM improved gas exchange and EELV (P<0.05). A significant correlation was found between Pao2 obtained 5 min after MVand EELV (R=0.41, P<0.001).

Conclusion: NPPV improves oxygenation and EELV in newborn compared with conventional preoxygenation. NPPV combined with early RM is more effective than NPPV at improving respiratory function after ETI.
Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group.
Authors: N Murray, P Coy, J L Pater, I Hodson, A Arnold, B C Zee, D Payne, E C Kostashuk, W K Evans, P Dixon
Journal: Journal of Clinical Oncology (1993)

PURPOSE The importance of the timing of thoracic irradiation (TI) in the combined modality therapy of limited-stage small-cell lung cancer (SCLC) was assessed in a randomized trial. METHODS All 308 eligible patients received cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) every 3 weeks for three cycles of each chemotherapy regimen. Patients randomized to early TI received 40 Gy in 15 fractions over 3 weeks to the primary site concurrent with the first cycle of EP (week 3), and late TI patients received the same radiation concurrent with the last cycle of EP (week 15). After completion of all chemotherapy and TI, patients without progressive disease received prophylactic cranial irradiation (25 Gy in 10 fractions over 2 weeks). RESULTS Although complete remission rates were not significantly different between the two arms, progression-free survival (P = .036) and overall survival (P = .008) were superior in the early TI arm. Patients in the late TI arm had a higher risk of brain metastases (P = .006). CONCLUSION The early administration of TI in the combined modality therapy of limited-stage SCLC is superior to late or consolidative TI.
Factors Influencing the Changing Clinical Expression of the Depressive Process in Children
Authors: LEON CYTRYN, DONALD H. MCKNEW
Journal: American Journal of Psychiatry (1974)

The authors attempt to conceptualize a pattern of defense against the depressive process that changes with age. They enumerate several forces that oppose or promote these defensive operations, resulting in three levels at which the depressive process manifests itself: fantasy, verbalization, and mood and behavior. The shifting balance of these forces helps to explain the variability with which the depressive process manifests itself throughout the various phases of the life cycle.
Antimicrobial susceptibility of 840 clinical isolates of Haemophilus influenzae collected in four European countries in 2000-2001
Authors: R. Blosser-Middleton, D.F. Sahm, C. Thornsberry, M.E. Jones, P.A. Hogan, I.A. Critchley, J.A. Karlowsky
Journal: Clinical Microbiology and Infection (2003)
The Mechanobiology of Aging
Authors: Jude M. Phillip, Ivie Aifuwa, Jeremy Walston, Denis Wirtz
Journal: Annual Review of Biomedical Engineering (2015)

Aging is a complex, multifaceted process that induces a myriad of physiological changes over an extended period of time. Aging is accompanied by major biochemical and biomechanical changes at macroscopic and microscopic length scales that affect not only tissues and organs but also cells and subcellular organelles. These changes include transcriptional and epigenetic modifications; changes in energy production within mitochondria; and alterations in the overall mechanics of cells, their nuclei, and their surrounding extracellular matrix. In addition, aging influences the ability of cells to sense changes in extracellular-matrix compliance (mechanosensation) and to transduce these changes into biochemical signals (mechanotransduction). Moreover, following a complex positive-feedback loop, aging is accompanied by changes in the composition and structure of the extracellular matrix, resulting in changes in the mechanics of connective tissues in older individuals. Consequently, these progressive dysfunctions facilitate many human pathologies and deficits that are associated with aging, including cardiovascular, musculoskeletal, and neurodegenerative disorders and diseases. Here, we critically review recent work highlighting some of the primary biophysical changes occurring in cells and tissues that accompany the aging process.
Innate and Adaptive Humoral Responses Coat Distinct Commensal Bacteria with Immunoglobulin A
Authors: Jeffrey J. Bunker, Theodore M. Flynn, Jason C. Koval, Dustin G. Shaw, Marlies Meisel, Benjamin D. McDonald, Isabel E. Ishizuka, Alexander L. Dent, Patrick C. Wilson, Bana Jabri, Dionysios A. Antonopoulos, Albert Bendelac
Journal: Immunity (2015)
Relaxant effect of crocus sativus (saffron) on guinea pig tracheal chains and its possible mechanism(s)
Authors: E. Assadpour, M.H. Boskabady, M.R. Aslani
Journal: European Respiratory Journal (2011)

The relaxant effects of 4 cumulative concentrations of aqueous-ethanolic extract and safranal were examined by their relaxant effects on precontracted tracheal chains of guinea pig by 10 μM methacholine (group 1) and 60 mM KCl in two different conditions including: non-incubated tissues (group 2) and incubated tissues with 1 μM propranolol 1 μM chlorpheniramine and 1 μM atropine (group 3), (n=6). In groups 1 and 2 all concentrations of theophilline, extract and safranal showed significant relaxant effects compared to that of saline (p Crocus sativus  showed a weak relaxant effect (p Crocus sativus  extract. These results showed a potent relaxant effect of  Crocus sativus  on tracheal chains of guinea pigs. The results also indicated the safranal is atleast, in part, responsible for the relaxant effect of  Crocus sativus .
Early detection of subclinical interstitial lung disease in patients with rheumatoid arthritis and effect of methotrexate therapy
Authors: Nasr Affara, Alaa Refaat, Mohamed Gawish
Journal: European Respiratory Journal (2014)

Objective: Early detection of Asymptomatic subclinical interstitial lung disease (ILD) (without respiratory symptoms) in patients with rheumatoid arthritis (RA) by high-resolution computed tomography (HRCT), chest radiography and pulmonary function tests (PFTs) and to study the possible role of methotrexate (MTX) therapy.

Patients &Methods: Fifty patients with RA were included in this study who attended Outpatient Clinics of Rheumatology and Chest Departments, Zagazig University Hospitals. They were 40 females and 10 males and classified into 2 groups according to MTX therapy and both groups were evaluated clinically, laboratory, pulmonary function tests (PFTs), chest radiography and by HRCT for detection of interstitial lung disease (ILD).

Results: that 46% (23/50) of RA patients were diagnosed as RA-ILD by HRCT and PFTs (30% (15/50) were in group 1 MTX therapy and 16 % (8/50) were in group 2, while 54% (27/50) did not meet criteria for ILD and were therefore designated as RA-no ILD. Compared with RA- ILD cases in group 2, RA-ILD patients in group 1were older and had longer disease duration, higher articular disease activity without significant difference; however they had more significant PFT and radiological abnormalities.

Conclusion: Lung involvement should always be considered in patients with RA particularly those on methotrexate therapy even in absence of chest symptoms. Diagnosis can be challenging since patients are unlikely to report dyspnea due to an overall decrease in physical activity with advanced arthritic symptoms. A tight control by PFTs, chest radiography and/orHRCT is binding and could affecting therapy plans.
Low-Dose Inhaled Corticosteroids and the Prevention of Death from Asthma
Authors: J C Kips, R A Pauwels
Journal: New England Journal of Medicine (2000)

Low-dose inhaled corticosteroids and the prevention of death from asthma

S Suissa, P Ernst, S Benayoun, M Baltzan, B Cai

Background: Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma. Methods: We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5–44 years of age who were using antiasthma drugs during the period 1975–1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage, whichever came first. We conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date. Results: The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46% of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose-response analysis, we calculated that the rate of death from asthma …
Which is the best source of mesenchymal cells to treat acute lung injury
Authors: Johnatas Silva, Ana Paz, Debora Xisto, Miquéias Lopes-Pacheco, Elga Bandeira, Milena Vasconcellos, Vera Capelozzi, Marcelo Morales, Paolo Pelosi, Elizabete Cirne-Lima, Patricia Rocco
Journal: European Respiratory Journal (2011)

Mesenchymal stem cells (MSC) may derive from bone marrow, adipose tissue or lung. Previous studies have shown that bone marrow derived mesenchymal stem cells (BM-MSC) exert beneficial effects in acute lung injury (ALI), but the effects of adipose tissue and lung derived mesenchymal cells (AD-MSC and L-MSC, respectively) have not been evaluated so far. The aim of this study was to investigate the effects of BM-MSC, AD-MSC, L-MSC on lung mechanics and morphometry, as well as inflammation and remodeling in an experimental model of ALI. Forty-eight female Wistar rats (200-250g) received Escherichia coli lipopolysaccharide (LPS) intratracheally (100 μg, ALI) or saline (C). At 48 hours, ALI and C groups were further randomized into subgroups receiving saline (0.05 mL), BM-MSC, AD-MSC, and L-MSC (1×10 5 ) intravenously. Bone marrow cells were extracted from four male Wistar rats. The induction of differentiation showed that cells from bone marrow, adipose tissue and lung were able to generate osteocytes, adipocytes and chondrocytes besides presenting CD34-, CD90+ and CD29+ profile. At day 7, mesenchymal cells promoted a reduction in lung static elastance, resistive and viscoelastic pressures, alveolar collapse, collagen fiber content and number of neutrophils in lung tissue, independent of the source. However, the beneficial effects of BM-MSC and AD-MSC on lung parenchyma remodeling were greater than those observed with L-MSC. In conclusion, in the present LPS-induced ALI model, BM-MSC and AD-MSC therapies were more effective than L-MSC at modulating inflammatory and fibrogenic processes.  Supported by: CAPES, PRONEX, FAPERJ, CNPq
Phase I trial of docetaxel and cisplatin in previously untreated patients with advanced non-small-cell lung cancer.
Authors: M J Millward, J Zalcberg, J F Bishop, L K Webster, A Zimet, D Rischin, G C Toner, J Laird, W Cosolo, M Urch, R Bruno, C Loret, R James, C Blanc
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacokinetics of the combination of docetaxel and cisplatin administered every 3 weeks to patients with advanced non-small-cell lung cancer (NSCLC) who have not received prior chemotherapy and to recommend a dose for phase II studies. PATIENTS AND METHODS Patients with advanced NSCLC and performance status 0 to 2 who had not received prior chemotherapy received docetaxel over 1 hour followed by cisplatin over 1 hour with hydration. Dose levels studied were (docetaxel/cisplatin) 50/75, 75/75, 75/100, and 100/75 mg/m2 repeated every 3 weeks. Colony-stimulating factor (CSF) support was not used. Pharmacokinetics of docetaxel and cisplatin were studied in the first cycle of therapy. Most patients (79%) had metastatic disease or intrathoracic recurrence after prior radiation and/or surgery. RESULTS Of 24 patients entered, all were assessable for toxicity and 18 for response. The MTD schedules were docetaxel 75 mg/m2 with cisplatin 100 mg/m2 (dose-limiting toxicities [DLTs] in five of six patients), and docetaxel 100 mg/m2 with cisplatin 75 mg/m2 (DLTs in two of two patients, including one fatal toxicity). Limiting toxicities were febrile neutropenia and nonhematologic, principally diarrhea and renal. Two patients had neutropenic enterocolitis. Pharmacokinetics of both drugs were consistent with results from single-agent studies, which suggests no major pharmacokinetic interaction. Neutropenia was related to docetaxel area under the plasma concentration-versus-time curve (AUC). An alternative schedule was investigated, with cisplatin being administered over 3 hours commencing 3 hours after docetaxel, but toxicity did not appear to be less. Independently reviewed responses occurred in eight of 18 patients (44%; 95% confidence interval, 22% to 69%), most following 75 mg/m2 of both drugs. CONCLUSION Docetaxel 75 mg/m2 over 1 hour followed by cisplatin 75 mg/m2 over 1 hour is recommended for phase II studies. The responses seen in this phase I study suggest a high degree of activity of this combination in previously untreated advanced NSCLC.
Conversion of the Hormonal Receptors on Recurrent Breast Cancer Patients
Authors: K. Fujii, M. Goto, Y. Imai, T. Ando, R. Tetsuka, J. Kosaka, Y. Shiomi, M. Yoshida, S. Nakano, T. Imai, T. Fukutomi
Journal: Annals of Oncology (2014)
Coronary Angioplasty Results in Leukocyte and Platelet Activation With Adhesion Molecule Expression
Authors: Carlos V. Serrano, José Antônio F. Ramires, Margareth Venturinelli, Siguemituso Arie, Elbio D’Amico, Jay L. Zweier, Fulvio Pileggi, Protasio L. da Luz
Journal: Journal of the American College of Cardiology (1997)

Objectives. This study sought to characterize leukocyte and platelet activation and adhesion molecule expression after coronary angioplasty. Background. Coronary angioplasty can be regarded as a clinical model of postischemic inflammation because this intervention leads to the release of inflammatory mediators as a result of plaque rupture and endothelial injury. Methods. In 13 patients with stable angina (mean [±SEM] age 56.0 ± 2.4 years, range 44 to 79), blood samples were drawn from the aorta and coronary sinus immediately before and immediately and 15 min after coronary angioplasty. Subsequently, leukocyte and platelet functions were determined. Eleven control patients (57.5 ± 2.3 years, range 52 to 78) underwent coronary arteriography. Results. Coronary arteriography and angioplasty showed no difference in number of leukocytes between the coronary sinus and the aorta. However, 15 min after coronary angioplasty, there was an increase in neutrophil CD18 and CD11b, monocyte CD14 and platelet glycoprotein IIb/IIIa expression and a decrease in neutrophil L-selectin expression (189 ± 25%, 163 ± 27%, 158 ± 35%, 141 ± 22% and 31 ± 10%, respectively, p < 0.01). In the control subjects, no change in adhesion molecule expression occurred. Superoxide production and aggregation in ex vivo-stimulated neutrophils collected from the coronary sinus 15 min after coronary angioplasty was significantly decreased compared with that after coronary arteriography (54 ± 12% vs. 106 ± 30% and 58 ± 11% vs. 102 ± 29%, respectively, p < 0.01). The reduced responses to phorbol ester stimulation may be explained by previous in vivo activation of neutrophils during coronary angioplasty. Conclusions. Coronary angioplasty increases neutrophil, monocyte and platelet adhesion molecule expression and induces a significant decrease in ex vivo-stimulated neutrophil superoxide generation and aggregation. These findings suggest that coronary angioplasty triggers cellular activation with an inflammatory response that could contribute to restenosis. (J Am Coll Cardiol 1997;29:1276–83)