tbuckley/cabot-search huggingface dataset:
A randomised controlled study to compare the efficacy of closed pleural biopsy and medical thoracoscopic pleural biopsy in undiagnosed exudative pleural effusion
Authors: Ravindran Chetambath, Nithya Haridas, K.P. Suraj, James Ponneduthamkuzhy Thomas
Journal: European Respiratory Journal (2011)

This study was to compare the efficacy of closed pleural biopsy with Abram9s needle and medical thoracoscopic biopsy in the diagnosis of undiagnosed exudative pleural effusion in a tertiary care setting. It was a randomised controlled study during the period Nov.2008- Oct.2010.  All patients admitted with pleural effusion, underwent a clinical workup for pleural effusion. Light9s criterion is used to differentiate between exudative and transudative pleural effusion. Those patient9s with exudative pleural effusion without the establishment of a specific diagnosis were included in the study. The enrolled patients were then randomised into 2 groups. One group was subjected to medical thoracoscopic pleural biopsy and the other to closed pleural biopsy with Abrahm9s needle. Demographic, clinical & biochemical charecteristics, diagnostic yield and the complications were of the two groups were compared.  58 patients were included in the study and they were divided into two groups of 29 patients each. The diagnostic yield was 86.2% in the medical thoracoscopy group as compared to 62.1% in closed pleural biopsy group. Complication rate was 10.3% in medical thoracoscopy group compared to 17.2% in closed pleural biopsy group. Hence the study concluded that medical thoracoscopic pleural biopsy had a better diagnostic yield with a lower complication rate as compared to closed pleural biopsy with Abrahm9s needle.
ICAM-1, GRP-78, and NFkB gene polymorphisms and clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated with first line 5-FU or capecitabine in combination with oxaliplatin and bevacizumab (FOLFOX/BV or XELOX/BV)
Authors: P. C. Manegold, A. B. El-Khoueiry, G. Lurje, H. Singh, D. Yang, W. Zhang, H. Chang, J. Shriki, A. Pohl, S. Iqbal, H. J. Lenz
Journal: Journal of Clinical Oncology (2008)

4134 Background: We evaluated polymorphisms of genes involved in angiogenesis, cell proliferation, and cell-cell or cell-matrix adhesion as potential predictors of clinical outcome in pts with mCRC who received BV as part of their frontline therapy. These genes included: VEGF, VEGF receptor 2, neuropilin 1, Interleukin 6 and 8, adrenomedullin, leptin, fibroblast growth factor receptor 4, tissue factor, matrix metalloproteinases 2,7,9, intracellular adhesion molecule-1 (ICAM1), glucose regulated protein 78 (GRP78), epidermal growth factor receptor, and nuclear factor kappa b (NFkB). Methods: PCR-RFLP assays were performed on genomic DNA extracted from the blood of pts with mCRC treated with first-line FOLFOX/BV or XELOX/BV at USC. Results: There were 59 pts (36 males, 23 females), median age: 56 years (range: 29–81). 38 pts received XELOX/BV and 21 pts FOLFOX/BV. Radiologic response: 2/59 (3%) complete response (CR), 35/59 (59%) partial response (PR), 18/59 (30.5%) stable disease and 4/59 (6%) progressive disease. At a median follow-up of 17.9 months (mo), 36/59 pts progressed with a median progression free survival (PFS) of 13.7 mo. Single nucleotide polymorphisms (SNP) C/T in ICAM1 (codon K469E, exon 6) and C/T in the 3’UTR region of GRP78 (rs12009 were significantly associated with response (CR+PR). Pts homozygous for the T allele in ICAM1 were found to have a lower probability of response (41%) compared to pts with the C/C (73%) or C/T (71%) genotypes (p=0.032). Pts with any C allele in the GRP78 gene (C/C; C/T) had a higher probability of response (89%; 64%) compared to pts homozygous for the T allele (T/T; 52%) (p=0.027). Significantly improved PFS was found in pts who had >24 CA repeats on at least one of the NFkB1 alleles located at 4q23–24 (15.5 mo [95% CI: 8.3–20.9+] for ≥24/≥24 genotype vs. 13.9 mo for <24/≥24 [95% CI: 13.0–38.6] vs. 7.2 mo [95% CI: 5.3–15.4] for <24/<24, p=0.023). Conclusions: This pilot study demonstrated, in a preliminary fashion, the potential predictive and prognostic value of ICAM-1, GRP78 and NFkB genomic polymorphisms in pts with mCRC treated with FOLFOX/BV or XELOX/BV. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech™ BioOncology, ImClone Systems Incorporated, Merck, Pfizer Oncology, Response Genetics Genentech™ BioOncology, Merck, Pfizer Oncology, Roche, sanofi-aventis
Antioxidant tetrapeptide UPF1 exerts an immediate effect on cigarette smoke-altered metabolic state of human bronchial epithelial cells
Authors: Argo Aug, Siiri Altraja, Kalle Kilk, Liisi Laaniste, Riina Mahlapuu, Ursel Soomets, Alan Altraja
Journal: European Respiratory Journal (2012)

We evaluated the protective capacity of UPF-1 (4-methoxy-L-tyrosinyl-γ-L-glutamyl-L-cysteinyl-glycine) against cigarette smoke condensate (CSC)-induced alterations in metabolic profile of human bronchial epithelial cells (HBEC).  HBEC were exposed to 10 µg/mL CSC for 1h, followed by treatment with 0-10 µM UPF1 or 2 mM N-acetylcysteine (NAC) for 1-12 h. Cell lysates were analysed on a Q-Trap 3200 mass spectrometer to obtain full spectra between mass-to-charge (m/z) ratios 50-1700 Da. Principal component analysis, partial least squares regression analysis and t-test were used.  Levels of many compounds (e.g. 226, 310, 408 Da) were significantly (p  Compared to NAC, the novel antioxidant tetrapeptide UPF1 acts effectively towards restoring the metabolic status in HBEC by eliminating the immediate effect of CSC. The results may speed up the design of drugs that facilitate prevention of COPD.  Supported by ESF grants 7856, 9043, 9103.
Molecular Pathways: Fatty Acid Synthase
Authors: Suzanne F. Jones, Jeffrey R. Infante
Journal: Clinical Cancer Research (2015)

Therapies that target tumor metabolism represent a new horizon in anticancer therapies. In particular, cancer cells are dependent on the generation of lipids, which are essential for cell membrane synthesis, modification of proteins, and localization of many oncogenic signal transduction enzymes. Because fatty acids are the building blocks of these important lipids, fatty acid synthase (FASN) emerges as a unique oncologic target. FASN inhibitors are being studied preclinically and beginning to transition to first-in-human trials. Early generation FASN inhibitors have been studied preclinically but were limited by their pharmacologic properties and side-effect profiles. A new generation of molecules, including GSK2194069, JNJ-54302833, IPI-9119, and TVB-2640, are in development, but only TVB-2640 has moved into the clinic. FASN inhibition, either alone or in combination, holds promise as a novel therapeutic approach for patients with cancer.
Abstract 1832: Location of Making Type 1 Electrocardiogram in Brugada Syndrome: Comparison between Lead Position and Anatomical Location of Right Ventricular Outflow Tract
Authors: Satoshi Nagase, Shigeki Hiramatsu, Nobuhiro Nishii, Masato Murakami, Takeshi Tada, Kohei Miyaji, Takefumi Oka, Kazufumi Nakamura, Kengo Kusano, Tohru Ohe
Journal: Circulation (2007)

Introduction: Recording type 1 ECG in right precordial leads in the presence or absence of a sodium channel blocker is a diagnostic criterion in Brugada syndrome (BrS). It was also suggested that right ventricular outflow tract (RVOT) is the arrhythmogenic substrate in BrS. However, we occasionally observed type 1 ECG only in the third intercostal space (3ics), not standard fourth intercostal space (4ics). Accordingly, we examined the relationship between the position of ECG leads manifesting type 1 and anatomical location of RVOT under fluoroscopic image. Methods: Total 33 BrS patients were examined in this study. All patients had more than one of the following: documented ventricular fibrillation (VF), several episodes of syncope, a family history of sudden death, SCN5A mutation or inducibility of VF by programmed electrical stimulation. Anatomical location of the RVOT was determined under fluoroscopic image with right ventriculography. ECG was also recorded at the 3ics in leads V1 and V2 in addition to the standard V1 and V2 at the 4ics with fluoroscopically visible electrodes. A pure sodium channel blocker, pilsicainide, was administered in all patients without manifesting type 1 ECG under baseline conditions. Relationships between anatomical location and the position of ECG leads manifesting type 1 were examined in all patients. Results: Type 1 ECG was recorded in all patients with pilsicainide administration. The location of RVOT corresponded with lead V1 and V2 at the 4ics in 5 patients and at the 3ics in 28 patients. In 4 out of 5 patients (80.0%) corresponding RVOT with 4ics, type 1 ECG was recorded at the 4ics. However, in 24 out of 28 patients (85.7%) corresponding RVOT with 3ics, type 1 ECG was recorded only at the 3ics. Furthermore, in 7 out of 12 symptomatic patients (58.3%) with documented VF or syncope, type 1 ECG was not recorded at the 4ics, however, could be detected at the 3ics without pilsicainide administration. The location of RVOT was not different between symptomatic and asymptomatic patients. Conclusions: Type 1 ECG is predominantly caused at the RVOT, and the relationship between the position of ECG lead and the RVOT is variable. Recording ECG at the 3ics in addition to the standard 4ics in the right precordial leads is convincing in diagnosis of BrS.
Prospective evaluation of asthma control using three different classification systems
Authors: Stephanie Korn, Julia Both, Marisa Hübner, Christian Taube, Roland Buhl
Journal: European Respiratory Journal (2011)

The goal of asthma treatment is to achieve and maintain current best control and reduce future risk of exacerbations and long-term morbidity. Aim of this study was to prospectively evaluate asthma control using GINA, ACQ (asthma control questionnaire) and ACT (asthma control test) in treated asthma patients in a real-life setting.  In 148 consecutive patients (48.6% male, age 46.3±14.5yrs., FEV1 2.6±0.9 L, FEV1 78.8±21.9% of pred.) who were routinely followed-up in our outpatient clinic asthma control was evaluated using GINA, ACQ and ACT. The GINA classification was taken as the “true” classification and ACQ and ACT scores as “predictor” classifications. The relationship between ACQ and ACT scores and GINA-defined controlled/partly controlled vs. uncontrolled asthma was evaluated with the ACQ cut-point ≥1.50 and ACT cut-point≤ 19 as tests for GINA uncontrolled status in terms of sensitivity, specificity as well as positive and negative predictive values.  The ACQ-7 and ACT correctly predicted GINA-defined uncontrolled asthma in 62.8% and 71.8% of patients, resp. Sensitivity was high with 88% for ACQ-7 and 94% for ACT, specificity was 56.8% and 69.2%, positive predictive value was 62.8% and 71.8% and negative predictive value was 85.2% and 93.1% (ACQ-7 and ACT). Similar results were obtained using ACQ-5. ACQ-7 and ACT detected significantly more patients having uncontrolled asthma compared to the GINA classification (p  Our results indicate that an ACQ score ≥1.50 and an ACT score ≤19 identify patients with uncontrolled asthma for whom a full clinical review is needed. ACQ and ACT are easily and rapidly completed by patients and can serve as useful tools in the clinic to assess asthma control.
A prediction-based resampling method for estimating the number of clusters in a dataset
Authors: Sandrine Dudoit, Jane Fridlyand
Journal: Genome biology (2002)

Microarray technology is increasingly being applied in biological and medical research to address a wide range of problems, such as the classification of tumors. An important statistical problem associated with tumor classification is the identification of new tumor classes using gene-expression profiles. Two essential aspects of this clustering problem are: to estimate the number of clusters, if any, in a dataset; and to allocate tumor samples to these clusters, and assess the confidence of cluster assignments for individual samples. Here we address the first of these problems.We have developed a new prediction-based resampling method, Clest, to estimate the number of clusters in a dataset. The performance of the new and existing methods were compared using simulated data and gene-expression data from four recently published cancer microarray studies. Clest was generally found to be more accurate and robust than the six existing methods considered in the study.Focusing on prediction accuracy in conjunction with resampling produces accurate and robust estimates of the number of clusters.
Interferon Alfa-2a as Compared with Conventional Chemotherapy for the Treatment of Chronic Myeloid Leukemia
Authors: Sante Tura, Michele Baccarani, Eliana Zuffa, Domenico Russo, Renato Fanin, Alfonso Zaccaria, Mauro Fiacchini
Journal: New England Journal of Medicine (1994)

In view of studies showing that interferon alfa was effective treatment for chronic myeloid leukemia and that it prolonged survival, we organized a prospective, controlled comparative study of this treatment.We compared recombinant interferon alfa-2a with conventional chemotherapy (hydroxyurea or busulfan) in a trial designed to have a power of 80 percent to detect a difference of 20 percent in median survival between the group given interferon and the group given conventional chemotherapy. Between 1986 and 1988, 322 patients with previously untreated or minimally treated Philadelphia chromosome-positive chronic myeloid leukemia were randomly assigned to treatment with either interferon alfa-2a (218 patients) or conventional chemotherapy (104 patients).The rate of karyotypic response (defined as > 33 percent of metaphases negative for the Philadelphia chromosome) was 30 percent in the interferon group and 5 percent in the conventional-chemotherapy group (P < 0.001). The time to progression from the chronic phase of leukemia to an accelerated or a blastic phase was longer in the interferon group than in the conventional-chemotherapy group (median, > 72 vs. 45 months; P < 0.001), as was survival (median, 72 vs. 52 months; 6-year survival, 50 percent vs. 29 percent; P = 0.002 for both comparisons). There was one treatment-related death in each group. Treatment was discontinued because of side effects (mainly influenza-like, gastrointestinal, or neurologic symptoms) in 35 patients given interferon alfa-2a (16 percent). The cost of interferon treatment was 200 times that of the conventional treatment.During long-term treatment of Philadelphia chromosome-positive chronic myeloid leukemia, interferon alfa-2a induced more karyotypic responses than conventional chemotherapy, delayed disease progression longer, and prolonged overall survival more.
Air trapping in relation to airways inflammation and bronchial responsiveness in patients with respiratory symptoms suggestive of asthma
Authors: Andrei Malinovschi, Asger Sverrild, Vibeke Backer, Celeste Porsbjerg
Journal: European Respiratory Journal (2014)

Air trapping is a known component of asthma disease and its relation to airways inflammation and bronchial responsiveness has been limitedly studied. Exhaled NO (FeNO) is a marker of Th2-related airways inflammation in asthma. Air trapping has been reported to relate to bronchial responsiveness (BR) to methacholine in unobstructed subjects with mild respiratory symptoms.

A total of 168 subjects with respiratory symptoms suggestive of asthma underwent clinical examination, lung function, FeNO and alveolar NO (CalvNO) measurements, methacholine and mannitol provocations and had asthma control (ACQ) and asthma-related life-quality (miniAQLQ) assessed.

Air trapping (RV/TLC-ratio of > 120 %predicted) was found in 16 subjects. Air trapping was related to poorer ACQ: 1.8 (1.3, 2.8) vs. 1.2 (0.4, 1.8), p=0.003 and miniAQLQ: 4 (3, 5.5) vs 5 (4, 7), p=0.01. Subjects with air trapping had a higher degree of BR to methacholine (RDR(median(IQR)): 43.1 (27.0, 93.3) vs 6.7 (2.0, 22.2), p<0.001) and mannitol (RDR 0.03 (0.02, 0.12) vs 0.02 (0.01, 0.03), p=0.01) than subjects without air trapping. Air trapping was also related to lower FEV1 (77± 15% predicted vs 98 ± 15%, p<0.001) and FVC (84% ± 10% vs 100 ± 15%, p<0.001). Similar levels of FeNO and CalvNO were found in both groups: 19.4 (11.3, 30.4) vs 16.7 (11.2, 27.3), p=0.87 and1.1 (0.3, 1.9) vs 0.9 (0.3, 1.5), p=0.49.

Air trapping was related to poorer asthma control, asthma-related life quality, and signs of airway responsiveness in the present study. However air trapping was not related to increased Th2-related airways inflammation. The clinical importance of these findings warrants further studies.
Ginger induces apoptosis and autophagocytosis in ovarian cancer cells
Authors: Jennifer M. Rhode, Jennifer Huang, Sarah Fogoros, Lijun Tan, Suzanna Zick, J. Rebecca Liu
Journal: Cancer Research (2006)

4510   Objective: The ginger components [6]-gingerol, and [6]-paradol have been shown to interfere with carcinogenic processes in several cell types. Previously described mechanisms of action include inhibition of EGF-induced cell transformation and AP-1 activation and induction of apoptosis. Ginger exerts inhibitory effects on prostaglandin and leukotriene biosynthesis, indicating that the antineoplastic effects of gingerol are also associated with anti-oxidant and/or anti-inflammatory function. A pro-inflammatory state may contribute towards ovarian carcinogenesis. In the present study, we explored the response of ovarian cancer cells to ginger  in vitro . Methods: A panel of ovarian cancer cell lines was treated with ginger solubilized in DMSO. Pharmaceutical grade whole ginger extract standardized to 5% [6]-gingerol, was used. Cell viability was determined with sulforhodamine assays. Ginger effect on VEGF, IL-8 and PGE-2 expression was determined via ELISA assay. Apoptosis was determined by sub G0 analysis by flow cytometry, and by immunoblotting for expression of caspase-9. Morphologic analysis was performed using light and electron microscopy. Autophagy was determined by transiently transfecting cells with GFP labeled LC3 and quantifying activated LC3 using immunofluroescence microscopy. Results: Ginger induced cell death as determined with sulforhodamine assay in all ovarian cancer cell lines tested. The extent of apoptotic cell death as indicated by cleavage of caspase-9 by immunoblotting and Sub Go analysis by flow cytometry was less than expected, suggesting that non-apoptotic cell death was also occurring. Morphologic analysis indicated the presence of autophagy; this was confirmed by immunofluorescence microscopic examination of activated LC3-GFP in ginger treated cells. Ginger treatement also resulted in decreased production of VEGF, IL-8 and PGE-2 in ovarian cancer cells. Conclusion: Ginger induces cell death in ovarian cancer cells through apoptosis as well as the induction of autophagy. The majority of conventional chemotherapeutic agents induce apoptotic cell death. Because ginger can circumvent chemoresistance due to alterations in apoptotic signaling, it has the potential to be effective against chemoresistant disease. Our preliminary results indicate that ginger is a nutraceutical that may have significant therapeutic benefit for ovarian cancer patients.
The treatment of a destructive lung tuberculosis by valvular lung volume reduction on early terms of therapy
Authors: Nikolay Yakushenko, Irina Tabanakova, Marina Kondakova, Ludmila Archakova
Journal: European Respiratory Journal (2012)

Lung tuberculosis (TB) can be complicated by cavity forming. Patients with destructions in the Russian Federation in 2010 have made 49,0% from first time revealed lung TB, closing of lung cavities was achieved in 63,0% of cases. The lethality of this patients reaches 14,0% and frequency of early relapses – 30,0%. 60-70% of cases caused by drug resistant strains of Myc.Tuberculosis.  Objective: To increase the efficiency of treatment of a destructive lung tuberculosis by valvular lung volume reduction on early terms of therapy.  Material and Methods: The work is the result of supervision over 40 patients with lung TB. 47,5% of patients were smear-positive, drug resistant MBT - in 25,0%. Destructions defined in the top shares of lungs in 72,3% of patients, in 27,7% - in the bottom share (the sixth lung segment). Visualized cavities from 1,0 cm. To 21 patient during a chemotherapy was installed a non-return endobronchial valve (I gr.). The comparison group - 19 persons (II gr.) received only chemotherapy. Valve installation was made with flexible bronchoscope. In all patients with lower lobe cavity localization therapy was supplemented with artificial pneumoperitoneum.  Results: 70,0% of patients became smear-negative in a month, by 3 months - 100,0% of patients (33,3% and 77,8% in II gr). Destructions closed in 3 and 6 months in 38,0% and 90,5% in I gr., 15,8% and 57,9% in II gr.(p  Conclusions: Valvular lung volume reduction is an effective non-drug technique in complex treatment of lung tuberculosis, raising efficiency of treatment in 1,7 times on closing of destruction cavities by 6 month.
From Rationalization to Reason
Authors: SEY MOUR S. KETY
Journal: American Journal of Psychiatry (1974)

The author reminds the profession that psychiatry is a branch of medicine, that psychiatrists are physicians especially equipped to treat mental illness, and that the medical model of mental illness is valid, heuristic, and humanitarian. He presents new data bearing on the reliability of the diagnosis of schizophrenic illness and the importance of genetic factors in the transmission of that syndrome, arguing that the medical model is as appropriate for the major psychoses as it is for diabetes.
Comparisons of predictive performance of breathing pattern variabilities measured during T-piece, automatic tube compensation and pressure support ventilation for weaning ICU patients from mechanical ventilation
Authors: Mauo-Ying Bien, Yu Ru Kou, You Shui Lin, You-Lan Yang, Chung-Hung Shih
Journal: European Respiratory Journal (2011)

Objective: To compare the influence of different ventilatory supports on the predictive performance of breathing pattern variabilities (BPV) for extubation outcomes in ICU patients.

Methods: 68 ready-for-weaning patients were divided into success (n=45; ES) and failure (n=23; EF) groups based on their extubation outcomes. Breath-to-breath analyses of peak inspiratory flow (PIF), total breath duration, tidal volume and rapid shallow breathing index (BB-RSBI) were performed for three 30-min periods while patients randomly received T-piece, 100% inspiratory automatic tube compensation with 5 cmH2O PEEP (ATC) and 5 cmH2O pressure support ventilation with 5 cmH2O PEEP (PSV) trials. Coefficient of variations (CV) and SD1 and SD2 of the Poincare plot were analyzed to serve as BPV indices.

Results: Under all three trials, BPV in EF patients were smaller than in ES patients. ATC and PSV decreased the ability of certain BPV indices to discriminate ES from EF than T-piece trial. The areas under the ROC curve of these BPV indices were: T-piece > ATC > PSV. Analysis of the classification and regression tree indicated that during the T-piece trial, a SD1 of PIF > 3.36 L/min defined a group including all ES patients and the combination of a SD1 of PIF ≤ 3.36 L/min and a CV of BB-RSBI ≤ 0.23 defined a group of all EF patients. The decision strategies using SD1 of PIF and CV of BB-RSBI measured during ATC and PSV trials achieved a less clear separation of EF from ES.

Conclusions: BPV measurement during the T-piece trial is the best choice for predicting extubation outcome in ICU patients.
Cutaneous symptoms in a patient with cardiofaciocutaneous syndrome and increased ERK phosphorylation in skin fibroblasts
Authors: M. Terao, N. Sakai, S. Higashiyama, Y. Kotobuki, A. Tanemura, M. Wataya-Kaneda, M. Yutsudo, K. Ozono, I. Katayama
Journal: British Journal of Dermatology (2010)