tbuckley/cabot-search huggingface dataset:
Effects of hyperoxia and helium-hyperoxia on the cardiocirculatory responses to incremental exercise in hypoxaemic patients with advanced COPD
Authors: Marcos Nunes, Fernando Queiroga-Jr., Ethiane Meda, Gaspar Chiappa, Maria-Christina Machado, Luiz Eduardo Nery, J. Alberto Neder
Journal: European Respiratory Journal (2011)

Heliox breathing might positively impact upon the haemodynamic responses to exercise in non-hypoxaemic patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) (Chiappa, GR et al. Am J Respir Crit Care Med, 179:1004, 2009 ). There is, however, a lack of evidence of whether these beneficial effects would also be found in patients with more advanced cardiovascular impairment, i.e. , hipoxaemic, GOLD stage IV patients. On a double-blind study, 13 patients (FEV1= 35.4±9.1% pred; PaO2= 57.7±7.0 mmHg) were submitted to maximum incremental cardiopulmonary exercise tests while breathing hyperoxia (HiOX= 40% O2) or helium-hyperoxia (He-HiOX= 60% He/40% O2). Stroke volume (SV, mL) and cardiac output (CO, L/min) were non-invasively monitored by impedance cardiography ( PhysioFlow® , Manatec Inc, France). Peak work rate (WR) was improved with He-HiOX compared to HiOX (52±21 W vs. 46±18 W); in addition, end-expiratory lung volume (EELV) was slightly, albeit significantly, reduced (5.50±1.25 vs 5.61±1.30 L; p 0.05). In conclusion, hyperoxic heliox enhances the cardiocirculatory responses to exercise compared to hyperoxia alone in less hyperinflated patients with advanced, hypoxaemic COPD. These data indicate that increased operational lung volumes are related to deleterious haemodynamic effects in this patient sub-population.
Identification of complex oncogene signatures in human cancer specimens and cell lines
Authors: Stephen P. Ethier, Govindaraja Atikkuke, Ramsi Haddad
Journal: Clinical Cancer Research (2010)

Abstract Activated oncogenes are the genetic drivers of human cancer progression. Oncogenes become activated by structural DNA alterations including gene amplification accompanied by gene over expression, point mutations, and gene translocations/rearrangements. Data from recent clinical trials using targeted agents strongly suggest that clinical efficacy of these drugs is optimal when the target is an activated oncogene. However, it is also clear that even among patients that respond to drugs that target activated oncogenes, the level and duration of response is highly variable. One possible reason for heterogeneity in response to oncogene-targeted agents is the genomic context of a particular activated oncogene is not the same in all patients. Thus, the genomic context of an oncogene-target can have a dramatic influence on drug efficacy. Therefore, the ability to detect and diagnose complex oncogene signatures in human cancer specimens is vital for better predictions of the efficacy of targeted agents, and to design personalized therapeutic strategies. In our Oncogenomics laboratory, we have been working to identify candidate amplified and point mutated oncogenes in human breast, ovarian and lung cancer specimens and cell lines. To obtain individual oncogene signatures, we have used high resolution array comparative genomic hybridization coupled with a novel gene expression algorithm that allows for the identification of genes that are over expressed within amplicons in individual specimens, and Sequenom analysis for identification of point mutated oncogenes. These approaches have allowed us to elucidate complex oncogene signatures for over 50 cancer cell lines and specimens. Analysis of these data sets suggests that oncogene combinations across specimens is nearly random. Thus, knowing the status of one oncogene such as HER-2 does not predict what other oncogenes may be activated in the specimen or cell line. Indeed, we have observed HER-2 amplifications in the context of amplifications of oncogenes in the 11q12 or 8p11 amplicons, among others, and in the presence of absence of PIK3CA mutations. Furthermore, analysis of the effects of small molecule inhibitors of HER-2 at the level of cell survival/proliferation and gene expression demonstrated a dramatic effect of oncogene context on response to a targeted agent. In particular, PIK3CA mutations in the presence of HER-2 amplification and over expression was associated with a greatly attenuated response of the cells to the HER-2 targeted agent. Collectively, these results point to a need for a molecular diagnostic platform that can accurately identify the causal driving oncogenes in an individual cancer biopsy specimen in order to optimize clinical trial design, and develop personalized therapeutic strategies.
Chronic obstructive pulmonary disease (COPD) exacerbations and carotid artery plaques: The Rotterdam study
Authors: Lies Lahousse, Quirijn J.A. van den Bouwhuijsen, Daan W. Loth, Guy F. Joos, Albert Hofman, Jacqueline C.M. Witteman, Aad van der Lugt, Guy G. Brusselle, Bruno C. Stricker
Journal: European Respiratory Journal (2013)

Background:  COPD is an independent risk factor for the presence of carotid artery wall thickening and vulnerable lipid core plaques.  Aims:  To investigate whether the risk of carotid wall thickening and lipid core carotid artery plaques further increases when COPD subjects have frequent exacerbations.  Methods:  This study was part of the prospective population-based Rotterdam Study in subjects ≥55 years. COPD diagnosis was confirmed by spirometry. Frequent exacerbations were defined as having at least one exacerbation a year starting from incident COPD date. Carotid wall thickening was defined on ultrasonography, lipid core plaques were characterized on high-resolution MRI.  Results:  Conclusions:  The risk of carotid wall thickening and lipid core carotid plaques further increases when COPD subjects have at least one exacerbation a year.
Isolated renal mucormycosis
Authors: E Levy, M J Bia
Journal: Journal of the American Society of Nephrology (1995)

The 15th reported case of isolated renal mucormycosis (infection of the kidney with fungus of the order Mucorales, in the absence of infection elsewhere in the body) is presented. The patient was a 36-year-old human immunodeficiency virus-infected man, actively using iv drugs, who suffered 6 wk of flank pain and fever before diagnosis was made by percutaneous renal biopsy. He received 4 months of amphotericin B treatment, then no therapy for 6 months before dying with no evidence of mucormycosis. Isolated renal mucormycosis should be suspected in those with an underlying immunocompromising illness or history of iv drug use who have persistent flank pain and fever, but sterile urine cultures. Computed tomographic scanning with contrast should then be performed; findings of severe inflammation or bacterial infection, despite an indolent clinical course with sterile or nondiagnostic urine and blood cultures, are suggestive of isolated renal mucormycosis, and renal biopsy under computed tomographic guidance should be performed, despite the potential risk of disseminated infection. Although our patient was treated with amphotericin B alone, nephrectomy with or without amphotericin B therapy appears to be more likely to cure infection and relieve pain and constitutional symptoms.
Abstract 12797: Characteristics and Outcomes of Emergency Department Patients Treated with Thienopyridines: Results from the NCDR(R)
Authors: Deborah B Diercks, Micheal Kontos, Judd Hollander, DaJuanicia Holmes, Jorge Saucedo, Stephen D Wiviott, James De Lemos
Journal: Circulation (2011)

Background: Over the last 10 years the AHA/ACC guidelines have evolved to recommend that patients with definite unstable angina or Non-ST segment elevation myocardial infarction (NSTEMI) receive dual antiplatelet therapy that may include a thienopyridine on presentation . to the hospital. Determinants and outcomes associated with the administration of thienopyridines in the emergency department (ED) have not been well characterized. Methods: We examined thienopyridine use in 39,543 patients with NSTEMI included in the NCDR’s ACTION Registry®-GWTG™ (430 US hospitals) between1/2007 and 6/2010. Patients not seen initially in the ED, transferred in, not administered Clopidogrel or Prasugrel within 24 hours of presentation, or missing time data were excluded. We analyzed the patient demographics associated with ED administration and impact of ED thienopyridine administration on in-hospital outcomes. Results: Of the cohort 9564 (24.2%) received a thienopyridine in the ED. Factors independently associated with t...
Acute effects of incremental maximal exercise on balance in patients with COPD
Authors: Josiane Marques Felcar, Vanessa Suziane Probst, Carla Sachetim Vieira dos Santos, Lúcia Roza da Silva, Laís Regina Garcia Ribeiro, Myriam Fernanda Merli, Rubens Alexandre da Silva, Nidia Aparecida Hernandes, Fabio Pitta
Journal: European Respiratory Journal (2013)

Background: Chronic obstructive pulmonary disease (COPD) leads to impaired exercise capacity. Recent data suggests that patients with COPD may also present an impaired balance. However, the acute effects of incremental maximal exercise on balance in patients with COPD remain unknown. Aim: to verify the acute effects of maximum intensity incremental effort on balance in patients with COPD. Methods: In a cross sectional study, 27 patients with COPD (15 men; 67±8 years; forced expiratory value in the first second 41±15 % predicted) were included. Before and after performing an Incremental Shuttle Walking Test (ISWT), all patients had their static balance assessed by a force platform in four different conditions (standing with feet hip-width apart and eyes opened [SFHEO]; standing with feet hip-width apart and eyes closed [SFHEC]; standing in short base [SSB]; and one-legged stance test [OLST]). The main parameters for stabilographic analysis used were 95% confidence ellipse area of center of pressure (COP area in cm2) and mean velocity sway of COP (MVel in cm/s) for antero-posterior (A/P) and medial-lateral (M/L) direction of movement. Results: The mean walked distance during the ISWT was 436±138 m, corresponding to 68±19 % predicted. Balance was significantly impaired after the ISWT for the SFHEO condition (COP area before ISWT: 2.94 [1.53-5.29] cm2 versus after: 3.35 [1.85-5.36] cm2; p=0.03) and MVel A/P (before ISWT: 0.91 [0.74-1.25] cm/s versus after: 1.04[0.81-1.27] cm/s; p=0.04). No differences were observed for the other conditions. Conclusion: Static balance seems to be negatively and acutely affected by a maximal exercise in patients with COPD.
Irinotecan Combined With Bolus Fluorouracil, Continuous Infusion Fluorouracil, and High-Dose Leucovorin Every Two Weeks (LV5FU2 Regimen): A Clinical Dose-Finding and Pharmacokinetic Study in Patients With Pretreated Metastatic Colorectal Cancer
Authors: Michel Ducreux, Marc Ychou, Jean-François Seitz, Marc Bonnay, Alice Bexon, Jean-Pierre Armand, Monder Mahjoubi, Dominique Méry-Mignard, Philippe Rougier
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the maximum-tolerated dose (MTD) and recommended dose of irinotecan (CPT-11) in combination with fluorouracil (5-FU) and leucovorin (LV), using a biweekly LV5FU2 regimen and increasing doses of CPT-11, and to assess the efficacy of this combination in pretreated patients with colorectal cancer (CRC). PATIENTS AND METHODS: All patients had metastatic CRC and a World Health Organization performance status of 0 or 1. CPT-11 was administered over a 90-minute infusion every 2 weeks at a range of dose levels (100, 120, 150, 180, 200, 220, and 260 mg/m 2 ). LV5FU2 was started 1 hour after the end of the biweekly CPT-11 infusion and was also administered on day 2. RESULTS: Fifty-five patients were entered onto this trial; 549 cycles were administered. The MTD was not reached at 260 mg/m 2 , and a dose level of 300 mg/m 2 was added. The MTD as defined in the protocol was not reached at this dose level either, but all patients had cycles delayed and/or required a dose reduction. This dose was deemed to be the MTD. To take into account both the toxicity of and compliance with the biweekly schedule, the recommended CPT-11 dose was established at 180 to 200 mg/m 2 . Antitumor activity was observed at almost all dose levels, with an objective response rate of 22%. Median time to progression was 6.3 months and overall survival was 15 months. CONCLUSION: The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity. CPT-11 at 180 to 200 mg/m 2 in combination with LV5FU2 has been selected as the recommended dose for further studies.
A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study.
Authors: J T Thigpen, J A Blessing, P J DiSaia, E Yordan, L F Carson, C Evers
Journal: Journal of Clinical Oncology (1994)

PURPOSE From 1979 to 1984, 356 eligible patients with advanced or recurrent endometrial carcinoma no longer amenable to therapy with surgery, radiotherapy, or progestins were treated with doxorubicin alone or doxorubicin in combination with cyclophosphamide. PATIENTS AND METHODS Patients were randomized to receive doxorubicin 60 mg/m2 intravenously (i.v.) with or without cyclophosphamide 500 mg/m2 i.v. every 3 weeks for eight drug courses. All patients had received prior therapy with progestins with subsequent progression of disease. No patients had received prior therapy with cytotoxic drugs. Of 356 patients, 300 had measurable disease. RESULTS Among 132 patients treated with doxorubicin alone, there were seven complete responses (5%), 22 partial responses (17%), 73 with stable disease (55%), and 30 with increasing disease within 2 months of study entry (23%). For the 144 patients who received the combination, there were 18 complete responses (13%), 25 partial responses (17%), 75 with stable disease (52%), and 26 with increasing disease (18%). The median progression-free interval for those patients who received doxorubicin alone was 3.2 months, while it was 3.9 months for those who received the combination. The median survival duration for doxorubicin patients was 6.7 months, while it was 7.3 months for the combination patients. None of the unadjusted estimates of treatment differences are statistically significant. Prognostic features that had an impact on outcome included one factor associated with an increased likelihood of response (presence of measurable lung metastases) and four features associated with a poorer survival (poor performance status [PS] of 2 or 3, high pathologic grade, and presence of liver metastases or other intraabdominal disease). If these features are taken into account in multivariate analyses, there is no statistically significant evidence for differences in response rates (relative odds of response, 1.58; P = .06, one-tailed test), and survival duration is slightly longer in the combination regimen (17% reduction in death rate; P = .048). CONCLUSION The combination of doxorubicin plus cyclophosphamide thus appears to offer a small advantage over doxorubicin alone in the management of endometrial carcinoma at the expense of more frequent and severe myelosuppression and gastrointestinal toxicity.
Smoking Habits and Tar Levels in a New American Cancer Society Prospective Study of 1.2 Million Men and Women
Authors: S D Stellman, L Garfinkel
Journal: JNCI Journal of the National Cancer Institute (1986)

In 1982 the American Cancer Society (ACS) enrolled over 1.2 million American men and women in a prospective mortality study of cancer and other causes in relation to environmental and life-style factors. Biennial follow-up is planned through 1988. At the time of enrollment, 23.6% of the men and 20.0% of the women were current smokers of cigarettes. Compared with a similar ACS study of 1 million subjects enrolled 23 years earlier, among men the proportion of current smokers was halved and that of ex-smokers doubled, while among women the proportion of ever-smokers increased by 10% and that of ex-smokers quadrupled. Most smokers of filter cigarettes had smoked nonfiltered cigarettes earlier in life. The median year for switching to filters was 1964, the year of the first Surgeon General's report. More than one-third of male smokers' and one-half of female smokers' current brands had tar yields below 12 mg; less than 9% of male smokers' and 4% of female smokers' current brands had tar yields of 20.2 mg or more (nonfilters). The study population differed in many respects from the general U.S. population; the study population had, for example, a much higher average educational level. Nevertheless, distributions of smoking habits changed a few percentage points after adjustment to the educational level of the general population.
THE SMALL BLOOD VESSELS OF THE SKIN IN ACROCYANOSIS..
Authors: F. SAGHER, ELI DAVIS, J. SHESKLN, J. LANDAU
Journal: British Journal of Dermatology (1966)

Journal Article THE SMALL BLOOD VESSELS OF THE SKIN IN ACROCYANOSIS.: Comparison of Biomicroscopy and BiopsyFindings. Get access F. SAGHER, M.D., F. SAGHER, M.D. The Department of Dermatology and Venereology, Medical Outpatient Department "C" and Capallary Research Laboratory, Rothschild Hadassah University Hospital, Jerusalem, Israel Search for other works by this author on: Oxford Academic Google Scholar ELI DAVIS, M.D., ELI DAVIS, M.D. The Department of Dermatology and Venereology, Medical Outpatient Department "C" and Capallary Research Laboratory, Rothschild Hadassah University Hospital, Jerusalem, Israel Search for other works by this author on: Oxford Academic Google Scholar J. SHESKLN, M.D., J. SHESKLN, M.D. The Department of Dermatology and Venereology, Medical Outpatient Department "C" and Capallary Research Laboratory, Rothschild Hadassah University Hospital, Jerusalem, Israel Search for other works by this author on: Oxford Academic Google Scholar J. LANDAU, M.D. J. LANDAU, M.D. The Department of Dermatology and Venereology, Medical Outpatient Department "C" and Capallary Research Laboratory, Rothschild Hadassah University Hospital, Jerusalem, Israel Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 78, Issue 11, 1 November 1966, Pages 586–589, https://doi.org/10.1111/j.1365-2133.1966.tb12152.x Published: 01 November 1966
Abstract 2222: Angioscopic Findings of Neointimal Coverage over Sirolimus-Eluting Stents: One Year Follow-up Study
Authors: Masaki Awata, Jun-ichi Kotani, Shinsuke Nanto, Masaaki Uematsu, Takakazu Morozumi, Toshinari Onishi, Osamu Iida, Fusako Sera, Hitoshi Minamiguchi, Hirokuni Akahori, Masamichi Yano, Hiroki Yasui, Seiki Nagata
Journal: Circulation (2006)

Background:  The sirolimus-eluting stent (SES) is effective in reducing instent restenosis (ISR) beyond one year. However, neointima following SES implantation beyond one year has not been well understood.   Method:  We evaluated the neointima 11 ± 1 months after SES implantation using angioscopy (Vecmover, Clinical Supply), and compared the findings with those implanted with bare-metal stents (BMS). Angioscopy was performed in 26 patients (age 66 ± 8 years, male gender 85%) with 41 stents (15 SES and 26 BMS). Neointimal coverage was graded as:  Grade 0  = struts were exposed similarly to the time of implantation;  Grade 1  = struts were covered, but not embedded;  Grade 2  = struts were embedded by the neointima;  Grade 3  = struts were fully embedded and invisible by angioscopy. Presence of thrombi was also assessed.   Results:  Ninety-two % of BMS showed  Grade 3 , whereas only 13% of SES did. Sixty % of SES showed  grade 1 . Strikingly, complete absence of neointimal coverage was observed in a SES as long as 291 days after implantation. Four red thrombi and 2 white thrombi were detected, which were equally distributed in BMS and SES. In the entire cohort of angioscopic 41 observations, thrombi were significantly associated with  grade 0 –2  coverage (p = 0.004).   Conclusions:  At one year follow-up, SES still shows low grade neointimal coverage, which was strikingly different from BMS. Because low grade neointimal coverage related to thrombi, prolonged dual anti-platelet therapy may be preferred in DES implanted patients.
Early discharge of community acquired pneumonia (CAP) patients with community respiratory assessment services (RAS) follow up in a UK DGH
Authors: Usman Maqsood, Martin Doherty
Journal: European Respiratory Journal (2013)

Background:   Length of hospital stay is a major cost issue during current financial era. This study aims at evaluating the reduction length of hospital stay (LOS) of CAP patients by means of community follow up. RAS nurses monitored the patients after discharge and provided them with short burst oxygen and loaned nebulizers.   Objectives:   To look at the safety of early discharge of CAP patients with community follow up by respiratory nurses and evaluate the impact on hospital stay.   Methods:   The length of stay, 30 day mortality and re-admission rate of all patients (n=67) admitted with CAP during year 2011 and having RAS follow up was analysed retrospectively. The results were compared with BTS national CAP audit results (n=5430).   Results:   Based on the CURB65 score, 48% (n=32) of patients had low severity CAP, 27% (n=18) moderate severity CAP and 25% (n=17) high severity CAP. The severity of pneumonia closely matched national average. RAS follow up lasted from 0 to 26 days (median 7, SD 4). 60% patients (n=40) were discharged with home Nebs and 16% (n=11) with short burst oxygen. 30 day re-admission rate was 8.9% (n=6) as compared to 10.9% (n=579/5430))nationally. 30 day mortality rate was 1.4% (n=1) as compared to 3.8% (n=164/4370) nationally. Length of stay was from 0 to 22 days (median 3, SD 4) as compared to 0 to 62 (Median 5, SD 9). There is a reduction of 2 day of median stay as compared to national average.   Conclusion:   A Community Respiratory service initiated in a UK DGH appears to be safe and effective in reducing the length of hospital stay significantly and does not lead to increase in 30 day mortality and re-admission rates.