tbuckley/cabot-search huggingface dataset:
The cost and diagnostic efficacy of microbiological evaluation of exudative pleural effusion
Authors: Serpil Tekgül, Semra Bilaceroglu, Hatice Kuma, Ali Kadri Cirak, Sevket Ozkaya
Journal: European Respiratory Journal (2011)

Purpose: To evaluate the cost and diagnostic efficacy of microbiological studies of pleural fluids.

Method: Hospitalized patients with exudative pleural effusion were prospectively evaluated. The fluid samples were examined for Gram stain, acid-fast bacilli smear together with specific bacterial, fungal and mycobacterial cultures.

Results: Bacteriologic and EZN stains of the pleural fluids were negative in 89 cases included whereas fluid cultures were positive in 9 (10,1%) cases [3 (12,5%) of the 24 with tuberculous pleurisy and 6 (28,5%) of the 21 with empyema or other parapneumonic pleural effusion]. The cultures of the malignant, nonspecific and paramalignant fluids were negative. In cases with empyema or other parapneumonic pleural effusion and tuberculous pleurisy, no significant difference was determined between culture-positive and culture-negative cases regarding age, gender, fever or fluid LDH and glucose levels; positive cultures were more frequent in the presence of fluid purulence (55.6% versus 8.3%, p=0.046). In 5 (83.3%) of the 6 culture-positive and in 6 (40%) of the 15 culture-negative cases with empyema or other parapneumonic effusion, change in antibiotic treatment was necessary. The costs of the microbiological studies was 39.4 Euro for each case and 1735 Euro and 1419 Euro for cases with noninfectious and infectious fluids, respectively.

Conclusion: Diagnostic yield of the routine microbiological studies of pleural fluids was determined low. It was concluded that requesting microbiological studies of pleural fluids in cases strongly considered to have infection on clinical basis and/or in cases with purulent fluid would be more beneficial regarding diagnostic yield and cost.
An Overview of Phenylcyclopropylamine Derivatives: Biochemical and Biological Significance and Recent Developments
Authors: Mohammed Naseer Ahmed Khan, Takayoshi Suzuki, Naoki Miyata
Journal: Medicinal Research Reviews (2012)

Abstract trans ‐2‐Phencylcyclopropylamine (2‐ PCPA ), a potent, clinically used antidepressant, affects monoamine neurotransmitter levels by inhibiting the main metabolizing enzymes, monoamine oxidases ( MAO s). However, the antidepressant action of this compound was not fully explained by its effects on MAOs due to its wide variety of biological effects. 2‐ PCPA also affects depression‐associated pathophysiological pathways, and linked with increased levels of trace amines in brain, upregulation of GABA B receptors (where GABA is gamma amino butyric acid), modulation of phospholipid metabolism, and interference with various cytochrome P450 ( CYP ) enzymes. Consequently, despite its adverse effects and limited clinical applicability, 2‐ PCPA has attracted interest as a structural scaffold for the development of mechanism‐based inhibitors of various enzymes, including lysine‐specific demethylase 1 ( LSD 1), which is a possible target for cancer chemotherapy. In the recent years, many reports have appeared in the literature based on 2‐ PCPA scaffold and their potential medicinal implications. This review mainly focuses on the medicinal chemistry aspects including drug design, structure–activity relationships ( SAR ), biological and biochemical properties, and mechanism of actions of 2‐ PCPA and its derivatives. Furthermore, we also highlight recent advance in this area and discuss their future applications for beneficial therapeutic effects.
Oropharynx cancer (OPC) in TAX 324: Human papillomavirus (HPV) and survival.
Authors: M. R. Posner, J. H. Lorch, O. Goloubeva, M. Tan, L. Schumaker, N. J. Sarlis, R. I. Haddad, K. J. Cullen
Journal: Journal of Clinical Oncology (2010)

5525 Background: HPV is an important prognostic and biologic marker in OPC. The association between HPV and survival (OS) in OPC was examined in TAX324, a prospectively randomized, international, phase III trial of sequential therapy (ST) in patients (pts) with locally advanced squamous cell cancer of the head and neck. Methods: The TAX324 trial has been reported (Posner, NEJM, 2007). Accrual was completed in 2003. OS data were collected through 2008. Tissues from untreated OPC tumors were studied by PCR for HPV16. HPV status was linked to long-term OS, progression-free survival (PFS), and demographics. Results: Of 264 evaluable pts with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. Nodal and clinical stages were similar; however, HPV+ pts were significantly more likely to: be younger (54 vs. 58 yrs, p=0.02), be Caucasian (96% vs. 84%, p=0.03), have T1/T2 primary cancers (49% vs. 20%, p=0.001), and have a PS of 0 (77% vs. 49%, p=0.003). Median follow-up period (range) for HPV+ and HPV- pts were 8 3(77-93) and 82 (68-86) months (mo), respectively. OS was significantly better for HPV+ vs. HPV- pts, HR = 0.20 (0.10-0.38, p<0.0001). Median survival time for HPV- pts was 21 mo and not reached for HPV+ pts. Rates of OS and PFS from 1 to 5 yrs were significantly better for HPV+ vs. HPV- pts (Table, p <0.0001 for all comparisons*); at 5 yrs, 82% of HPV+ pts were alive compared to 35% of HPV- pts. There were too few pts to compare differences between TPF and PF in this subset. Conclusions: HPV+OPC has a different biology, demographics, and OS compared to HPV- OPC. Both the OS and PFS obtained with ST at 5 years in HPV+OPC are unprecedented. The excellent PFS predicts durable long-term OS. These data support the notion of developing different therapeutic approaches for HPV+ and HPV- OPC. Our data suggest that it might be possible to reduce long-term morbidity in HPV+OPC and preserve survival by reducing radiotherapy intensity in the context of ST, and that we might best approach HPV- disease with more aggressive ST and/or CRT. OS* HPV+ N=56 HPV- N=55 1-yr 93% (82-97) 69% (54-79) 2-yr 89% (78-95) 48% (34-61) 3-yr 87% (75-94) 41% (28-53) 5-yr 82% (69-90) 35% (23-48) PFS* 1-yr 85% (73-92) 52% (38-64) 2-yr 83% (70-91) 35% (23-48) 3-yr 81% (68-90) 33% (21-46) 5-yr 78% (64-87) 28% (17-40) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis
The antiemetic effects of oral azasetron in lung cancer patients treated with moderately emetogenic chemotherapy: Comparison with intravenous granisetron
Authors: Hirotoshi Iihara, Junki Endo, Maya Yamada, Kiyoyuki Kitaichi, Koumei Yanase, Fumihiko Kamiya, Fumitaka Ito, Norihiko Funaguchi, Yasushi Ohno, Shinya Minatoguchi, Yoshinori Itoh
Journal: European Respiratory Journal (2012)

Background:  Azasetron (AZA) and granisetron (GRN) were generally used as antiemetics during cancer chemotherapy. However, 5-HT3 receptor occupancy of these two drugs was quite different. The calculation based on pharmacokinetic information showed that AZA had a relatively higher 5-HT3 receptor occupancy (oral: 80%; intraveneous:85%) than GRN (oral: 57%; intraveneous:64%) at 24 h after treatment. In the present study, we conducted a randomized controlled noninferiority study comparing the antiemetic effects of oral AZA and intravenous GRN in patients receiving moderately emetogenic chemotherapy (MEC) for lung cancer.   Methods:  Patients with lung cancer who received MEC were randomly assigned to oral AZA (10mg) and intravenous GRN (3mg). The primary end point was complete antiemetic response (no emesis, no moderate to severe nausea, and no rescue treatment; CR) during acute (0-24 h) period. CR during delayed (24-120 h) period and hematological toxicities were also monitored.   Results:  CR during acute period was not different between oral AZA and intravenous GRN. There were also no significant differences in CR during delayed (24-120 h) period and the incidence of hematological toxicities between oral AZA and intravenous GRN.   Conclusion:  Oral AZA was shown to be noninferior to intravenous GRN in the antiemetic effect against MEC. Thus, the use of oral AZA would be cost-beneficial for cancer chemotherapy.
Effects of Thymectomy and Antithymocyte Serum on Spontaneous Regression of Friend Virus-Induced Erythroleukemia 2
Authors: Michael Dietz, Philip Furmanski, Rodney Clymer, Marvin A. Rich
Journal: JNCI Journal of the National Cancer Institute (1976)

To evaluate the role of immune response in regression of leukemia, we studied the effect of immunosuppression on the spontaneous regression of a leukemia induced by a specific strain of Friend murine leukemia virus complex (RFV). Thymectomy of newborn but not adult outbred Swiss mice markedly inhibited regression. The effect of antithymocyte serum (ATS) on regression depended on the timing of ATS treatment. Regression was markedly inhibited in leukemic mice given ATS just before the start of regression. During leukemia development, ATS treatment but not thymectomy potentiated splenomegaly and delayed the start of regression. Both ATS treatment and neonatal thymectomy increased mortality as a function of the decrease in disease regression. Treatment with normal rabbit serum also inhibited regression but, when given during leukemia development, affected neither the splenomegalic response to RFV nor the number of deaths. The data demonstrated that an intact immune system was required for leukemia regression and suggested that some thymus-dependent parameter of immune response was a major factor in regression.
Production of Endogenous Nitric Oxide in Chronic Obstructive Pulmonary Disease and Patients with Cor Pulmonale
Authors: ENRICO CLINI, GEORGE CREMONA, MARCO CAMPANA, CARLA SCOTTI, MARCO PAGANI, LUCA BIANCHI, AMERIGO GIORDANO, NICOLINO AMBROSINO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Exhaled nitric oxide (NO) production in stable chronic obstructive pulmonary disease (COPD) has been loosely related to the severity of illness, being significantly reduced in the most severe cases. Pulmonary hypertension is associated with lower NO output from the lung. In this study expired NO was measured in patients with severe stable COPD with or without cor pulmonale (CP). Echocardiographic estimates of right heart function, lung function, diffusion capacity, respiratory muscle strength, and arterial blood gases were obtained in 34 consecutive patients with stable COPD (mean age, 68 +/- 7 yr). Expired NO was measured by chemiluminiscence to obtain fractional exhaled concentrations at peak (FENOp) and at plateau (FENOpl) points of the single-breath curve and resting NO output (V NO). All measurements of expired NO output, FENOp, FENOpl and V NO showed a negative correlation with both systolic pulmonary artery pressure (Pspa) (r = -0.51, -0.63, and -0.63, respectively, p < 0.01 for all) and right ventricle wall dimension (r = -0.41, -0.59, and -0.43, respectively, p < 0.05 for all), but not with any measurement of lung function. When the patients were divided according to the Pspa using a cutoff limit of 35 mm Hg, those subjects with CP showed lower FENOp (13.2 +/- 4.0 versus 36.7 +/- 30.8 ppb, p < 0.05), FENOpl (5.7 +/- 1.9 versus 8.9 +/- 4.7 ppb, p < 0.05), and V NO (69. 2 +/- 5.6 versus 107.6 +/- 14.6 nl/ min, p = 0.02) than did those with a normal resting Pspa. NO production from the airways was significantly lower and inversely related to development of CP in patients with severe COPD. Impaired endothelial release may account for the reduced levels of expired NO.
Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report.
Authors: N L Bartlett, S A Rosenberg, R T Hoppe, S L Hancock, S J Horning
Journal: Journal of Clinical Oncology (1995)

PURPOSE Although survival rates have improved for patients with bulky and advanced-stage Hodgkin's disease (HD), current treatments entail substantial acute morbidity and risks for late effects such as infertility, second malignancies, and cardiopulmonary toxicities. A novel, brief chemotherapy regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone [Stanford V]) was designed to shorten the duration of treatment, significantly reduce cumulative doses of alkylating agents, doxorubicin, and bleomycin, and maintain dose-intensity (DI). This brief chemotherapy was combined with radiation therapy (RT) to bulky disease sites. METHODS Since May 1989, 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement (n = 21) or for stage III or IV HD (n = 44). Patients received weekly chemotherapy for 12 weeks. Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy; in the remaining 40 patients, RT was limited to bulky disease (adenopathy &gt; or = 5 cm and/or macroscopic splenic nodules defined by computed tomography [CT]). RESULTS With a median follow-up period of 2 years, actuarial 3-year survival rate is 96% and failure-free survival (FFS) rate is 87%. The 3-year FFS rate is 100% for stage II patients with bulky mediastinal disease and 82% for patients with stage III to IV disease. There were no treatment-related deaths. In a preliminary analysis on a subset of patients, female and male fertility appears to be preserved. CONCLUSION These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky, limited-stage, and advanced-stage HD. Less cumulative exposure to alkylating agents, doxorubicin, and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity. Based on these results, the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a randomized clinical trial.
Approach to transbronchial biopsy with endobronchial ultrasound for small solid and ground glass opacity peripheral lung cancer
Authors: Christine Chavez, Shinji Sasada, Takehiro Izumo, Junko Watanabe, Masahiro Katsurada, Takaaki Tsuchida
Journal: European Respiratory Journal (2014)

Background and Objective:  Radial endobronchial ultrasound with a guide sheath (EBUS-GS) has improved the diagnostic accuracy of transbronchial biopsy (TBB) for malignant peripheral pulmonary nodules (PPNs). Studies on its utility have mainly included solid PPNs but considering that more ground glass opacities (GGOs) are being detected these days, we aimed to find an approach that can further improve the efficacy of the procedure based on nodule characteristics.   Methods:  This was a retrospective study on 212 malignant PPNs that underwent EBUS-GS TBB at the National Cancer Center, Tokyo, Japan, from April 2012 to March 2013.   Results.  The PPNs measured 20 mm (mean, SD 5.45) and were mainly adenocarcinoma. EBUS-GS established the diagnosis in 68%, with a positive likelihood ratio of 2.57 (1.42 to 4.64) and a negative likelihood ratio of 0.37 (0.27 to 0.52). For solid PPNs (N=117), significant improvement of yield to 78% was noted for centrally located nodules  (p= 0.01)  and when the EBUS probe was within the tumor  (p= 0.01) . For GGO (N= 95), factors that significantly increased the yield to 75-77% were central location  (p= 0.05) , EBUS probe within the tumor  (p= 0.01) , and when at least 5 histologic samples were collected  (p= 0.01) . Nodule size, lung field, and GS size did not contribute substantially to the efficacy of the procedure.   Conclusion.  TBB with EBUS-GS is a satisfactory diagnostic procedure for both solid and GGO peripheral lung cancer but better accuracy can be expected for proximally located PPNs and those that can be precisely detected by EBUS. For GGO, adequate tissue sampling is recommended.
Outcome of pulmonary rehabilitation in patients after acute exacerbation of chronic obstructive pulmonary disease
Authors: T.H. Deepak, Prasanta Mohapatra, Ashok Janmeja, Parul Sood, Monika Gupta, Deepak Aggarwal, C. Prashanth, Robin Gupta, Rahul Katyal
Journal: European Respiratory Journal (2013)

Introduction   COPD is associated with impaired exercise performance and functional capacity. Pulmonary rehabilitation in COPD is an evidence based intervention which improves the exercise capacity and quality of life.   Aims and Objectives   To evaluate the effect of early pulmonary rehabilitation after an acute exacerbation on exercise capacity and quality of life in patients with COPD.   Methods   We evaluated the benefits of early pulmonary rehabilitation in patients with COPD following acute exacerbation.Sixty patients with recent history of acute exacerbation were enrolled into the study. Baseline evaluation and randomization was done allotting 30 patients each into the intervention and control groups.Patients in both the groups received the standard management of COPD. While only the intervention group underwent a 12 week pulmonary rehabilitation program in addition.The exercise capacity was assessed by six minute walk distance (6MWD). St. George’s respiratory questionnaire (SGRQ) was used to measure the quality of life. Assessment of both these parameters was made at the beginning of the study and at the end of three months.   Results   The baseline characteristics of both the groups were found to be similar. The mean 6MWD value increased by 37.9 meters in the intervention group and the change was significant (p   Conclusions   Early pulmonary rehabilitation after an acute exacerbation of COPD has significant benefits on the quality of life and exercise capacity of the patients and should be imbibed into the standard management protocol for COPD.
Experimental fatal pneumonia due to Burkholderia cenocepacia: Differential involvement of toll-like receptors (TLRs) 4 and 5
Authors: Viviane Balloy, Heidi Nagel, Reuben Ramphal, Mustapha Si-Tahar, Michel Chignard
Journal: European Respiratory Journal (2011)

As shown in a previous study (Ventura et al., 2009), MyD88, a key downstream adapter for most of the TLRs, is involved in the inflammatory response responsible to the death due to B. cenocepacia pneumonia.  The aim of the present study was to determine which TLRs were involved in this response. We specifically focused on the TLRs 4 and 5, as these two receptors are the main ones involved in the recognition of P. aeruginosa, a flagellated Gram-negative bacterium like B. cenocepacia.  Mice deficient for TLR4, TLR5 or both were infected intratracheally with a suspension of B. cenocepacia and animal survival was observed daily. Alternatively, bronchoalveolar lavages were collected at different time points to further determine cytokine concentrations and the number of CFU of B. cenocepacia.  We observed that the inflammatory response of the host to B. cenocepacia lung infection was due to TLR4 and not to TLR5. As for the MyD88-/- strain, TLR4-/- mice were protected from death and cytokine and chemokine synthesis in response to infection were reduced. By contrast, we observed a reduced pathogen burden in the case of TLR4-/- mice compared to the enhanced (but transient) pathogen burden observed with MyD88-/- mice, suggesting that another TLR was involved in bacterial clearance.  The data clearly demonstrate a detrimental role of TLR4 for the host upon B. cenocepacia lung infection.   Reference:   1Ventura et al., J Immunol. 2009;183:670-6.
Evaluation of neurological symptoms in oncologic patients at the emergency department
Authors: A. Ferrer, D. López, M. Vidal, M. Tobeña, S. Serrano, I. Pajares, E. Millastre, M. Ruiz-Echarri, J. Lambea, A. Tres
Journal: Journal of Clinical Oncology (2009)

e20728 Background: Neurological symptoms in cancer patients are common and some of them represent a potentially serious situation. They are a frequent cause of complaint at the Emergency Department (ED). The aim of the study is to describe the profile of cancer patient who consult at ED for neurological symptoms, their diagnosis and management. Methods: From October 2007 to October 2008, all cancer patients treated at the ED of our hospital were prospectively collected. The reasons for consultation, diagnosis and clinical management are described. Results: A total of 560 cancer patients were enrolled. Of them, 61 patients (11%) consulted for a neurologic symptom: 50 of these patients (82%) were stage IV disease and 30 (49,2%) were receiving chemotherapy treatment. Of the total of patients, 14 (23%) had lung cancer; 10 patients (16%) had colorectal cancer; and 8 patients (13%) had primary central nervous system tumor. Most frequent causes of complaint were: low level of consciousness, 13 patients (21%); mobility deficit, 12 patients (19%); syncope, 9 patients (15%) and comitial crisis, 6 patients (10%). Of the patients who consulted for a neurological symptom, 52% of cases (32 patients) the cause was a structural lesion of central nervous system. Tumor progression was the diagnosis made in 27 patients (44,3%), in 14 patients (23%) the diagnosis was a metabolic alteration. A 69% of patients (42 patients) required hospitalization, 26% was discharged (16 patients) and 5% (3 patients) needed to be under observation during at least 24 hours. Conclusions: Neurological symptom is a frequent cause of complaint at ED for cancer patients. especially in patients in advanced stages. The most frequent diagnosis made because of these symptoms is tumor progression. Metabolic alterations are also an important diagnosis because of their frequency and because they can be solved by medical treatment. Most patients who consult for neurological symptoms need hospitalization. No significant financial relationships to disclose.
A simple method based on fluorescence probes for cancer diagnosis
Authors: Ta-Chau Chang, Chi-Chih Kang
Journal: Clinical Cancer Research (2010)

Abstract A simple, rapid, and noninvasive method at low cost based on fluorescence of 3,6-Bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) staining was applied for point-of-care screening of cancer cells [1]. Further application to clinic malignant neck lumps showed that the diagnostic accuracy of this simple method alone is ~80 % [2]. In addition, the combination of the BMVC test and the fine-needle aspiration (FNA) cytology can reduce the non-diagnostic cases and improve the diagnostic accuracy. Since a small amount of the sample collected for clinic test is used for BMVC test, it can be widely used in Hospital and Medical Center either for a first-line screening tool or an adjuvant method to other methods for cancer diagnosis. The success of the BMVC test for cancer diagnosis is mainly due to two distinct properties of BMVC: significant increase of the fluorescence quantum yield upon interaction with DNA and dramatic difference in the intracellular localization between the nucleus of cancer cells and the lysosome of normal cells. Here we have modified the molecular properties of BMVC derivatives to elucidate the possible correlation between molecular structure and cellular localization. Moreover, a better fluorescence probe than BMVC is screened for the detection of a single cancer cell by optimizing fluorescence contrast between cancer cells and normal cells by using a simple device. Our results not only provide invaluable information for targeting specific cellular organelles, but also establish new molecular principles for cancer diagnosis and treatment design. Further experiments show that BMVC can kill the CL1-0 cancer cells, but less damage the MRC-5 normal cells after irradiation at ~480 nm for several seconds. 1. Kang, C.C. et al. Analyst 132, 745-9 (2007). 2. Liao, L.J. et al. Analyst 134, 708-11 (2009).