tbuckley/cabot-search huggingface dataset:
Circulating free DNA as a surrogate for tumor material for EGFR and KRAS analysis
Authors: Gillian Ellison, James Sherwood, Carolyn Gokhale, Andrew Wallace, Robert Elles, Anderson Ryan
Journal: Clinical Cancer Research (2010)

Abstract The analysis of a patient's tumor mutation status has become increasingly important. Pharmaceuticals such as gefitinib require that a mutation test is performed prior to treatment to help predict a positive outcome to the patient before the drug is administered. However, obtaining a suitable tumor sample for analysis is not always possible and therefore some patients that may benefit will not receive the drug. The use of easily obtainable samples such as plasma or serum would be ideal if tumor derived material could be readily extracted and contained the same predictive mutations as the source tumor. We have evaluated circulating free (cf) DNA from plasma, and to a lesser extent serum, from lung cancer patients for EGFR and KRAS mutations using allele specific PCR tests (ARMSTM). The majority of the samples had no matched tumor sample available so the mutation detection rate was compared to the expected frequency of mutations in this tumor and population type. EGFR mutations were detected in 21 of 237 plasma cf DNA samples (8.9%) (expected: 10-15%). KRAS mutations were detected in 11 of 168 plasma cf DNA samples (6.6%) (expected: 17%). Where analysis was performed on the matched cf DNA extracted from serum the mutation detection rate was lower than in plasma. Interestingly the EGFR mutation frequency was higher than KRAS in the plasma samples, although the KRAS mutation frequency was expected to be higher than EGFR mutation frequency in the tumors. This could be due to the frequent amplification of mutant EGFR in lung tumors resulting in more target copies in the cf DNA, the EGFR assays could be more sensitive or perhaps the nature of EGFR mutation containing tumors is different making them shed more DNA or survive longer in the blood. In conclusion, cf DNA derived from plasma is a useful surrogate for mutation detection when no tumor sample is available, but the mutation detection rate is not equal for different mutations in different genes.
A Potential Link between Serum Low-Density Lipoproteins and Asthma
Authors: Nicola Scichilone, Manfredi Rizzo
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

drugs, such as age, bronchodilator reversibility, and history of or current tobacco use.Naturally, some criteria may be warranted by the trial methodology to reach the primary endpoint.For example, the minimum exacerbation rate in the previous year may guarantee a sufficient number of events to avoid studies being prolonged if the primary endpoint is the time until the first exacerbation.These administrative and financial constraints should not, however, affect the scientific value of these studies, and the results should remain able to be extrapolated to excluded populations.Patients included in RCTs are young, are recently diagnosed, are healthy other than their asthma, have moderate to severe rather than very severe asthma, and have never been heavy smokers.Because current guidelines such as GINA rely on results from such exclusive RCTs, this calls into question the extent to which these guidelines are applicable to daily practice.
Clinical assessment of the risk of violence among psychiatric inpatients
Authors: D E McNiel, R L Binder
Journal: American Journal of Psychiatry (1991)

The authors evaluated the reliability and validity of a probabilistic approach to clinical assessment of short-term risk of violence.At admission, nurses and physicians independently rated the probability that each of 149 psychiatric patients would physically attack someone during the first week of hospitalization on a university-based locked inpatient unit. Ward behavior was measured with the Overt Aggression Scale.There was a moderate level of agreement between nurses' and physicians' assessments of risk. Ratings of ward behavior showed an increase in the proportion of assaultive patients as the level of estimated risk of violence increased. Although the overall rate of assaults was overpredicted, there was a close correspondence between clinical estimates of patients' chances of becoming violent and the proportion of patients within each risk level who later displayed some type of inpatient aggression.The reliability and validity of short-term estimates of the risk of violence among acutely disturbed inpatients may be higher than past violence research has suggested. These findings provide preliminary support for the utility of a probabilistic approach to assessment of the risk of violence.
Adjuvant chemotherapy of osteosarcoma.
Authors: F R Eilber, G Rosen
Journal: Journal of Clinical Oncology (1987)

From this review of chemotherapy trials, several observations can be made. Osteosarcoma is a complex disease involving multiple histologies, each with a different prognosis. Prognostic factors that have been shown to be important include anatomic location of the primary tumor, stage at presentation (patients with metastatic or local recurrent disease fair far worse than those with primary disease), age at onset (children fair worse than the teenager with osteosarcoma), and location within the extremity (patients with more distal tumors fairing better than patients with more proximal tumors). There is convincing evidence for the efficacy of chemotherapeutic agents such as methotrexate in high doses (at least 8 g/m2 for adults, 12 g/m2 for children), Adriamycin, and cisplatin. The combination of Adriamycin and cisplatin appears to be more beneficial relative to either one of these agents alone. The efficacy of the combination of BCD as a triple-drug regimen, although useful in several different trials, has not been convincingly shown. Finally, from several of the recent randomized trials, it appears, that chemotherapeutic regimens containing an Adriamycin and cisplatin combination appear to be superior to those that do not include this combination. However, these observations are made from a historical perspective and have not been conclusively proven by randomized prospective investigations. The observations concerning the natural history of the disease and the activity of various chemotherapeutic agents suggest certain clinical practice algorithms. Essential staging procedures would include a bone scan looking for multifocal or metastatic disease, and CT scans of the chest looking for metastases to the lung. From all studies, it is apparent that surgery is mandatory for the primary tumor and should be an integral portion of all treatment methods. Chemotherapy should be considered for all patients with osteosarcoma, and the essential drugs in the regimen appear at present to minimally include high-dose methotrexate, Adriamycin, and cisplatin. It would also appear from several of these reports that not only is the adjuvant use of these chemotherapeutic agents indicated, but that the preoperative use of these agents has had significant advantages. The neoadjuvant chemotherapy begins the essential systemic chemotherapy at a very early stage, allows histologic assessment of treatment effect, permits altering drug regimens postoperative, and in many reported trials has allowed less than amputative surgery (limb salvage) to be performed. Finally, close follow-up of patients with osteosarcoma has therapeutic value.(ABSTRACT TRUNCATED AT 400 WORDS)
A putative tumor suppressor role for Wnt-signaling in sarcomagenesis
Authors: I. Matushansky, N. Socci, E. Hernando, S. Singer, G. Schwartz, C. Cordon-Cardo, R. Maki
Journal: Journal of Clinical Oncology (2006)

9507 Background: We sought to elucidate the relationship between the human adult mesenchymal stem cell (hMSC), Wnt signaling and sarcomagenesis. Methods: In vitro hMSC differentiation, microarray gene expression analysis, distance correlation analysis, and standard molecular biology techniques were used to explore the role of Wnt in controlling the differentiation of both hMSCs and high grade undifferentiated sarcoma (HGUS; MFH, malignant fibrous histiocytoma), a common form of adult soft tissue sarcoma. Results: We determined that 1) hMSCs appear to be the progenitor cells of HGUS/MFH; 2) Dickkopf-1 (Dkk1), a specific inhibitor of Wnt signaling, is overexpressed in MFH as compared to other sarcoma subtypes and is involved in the proliferation of hMSCs; 3) in hMSCs, Dkk1 levels decline and nuclear β-catenin accumulates as hMSCs reach confluence, a prerequisite for initiation of in vitro differentiation, while in an MFH cell line Dkk1 levels do not decline and there is no nuclear β-catenin accumulation; 3) MFH cells appear to be primed for differentiation and express early markers of mesenchymal differentiation, then undergo apoptosis, if nuclear β-catenin is manipulated to enter the nucleus; 4) Wnt2 signals via the canonical β-catenin pathway and is responsible for “commitment” of hMSC and an MFH cell line to various differentiation pathways, while Wnt5a signals via the non-canonical JNK pathway in preventing apoptosis upon appropriate commitment toward differentiation. Conclusions: We identified the contribution of canonical and non-canonical Wnt signaling in the differentiation of hMSCs and showed that enhancing signaling via these pathways could be exploited as a potential target for therapy for high grade undifferentiated sarcomas. These data implicate Wnt-signaling as a mechanism of tumor suppression in early sarcomagenesis. No significant financial relationships to disclose.
Living with COPD: A perspective on patients' concerns
Authors: Cristina Jácome, Raquel Gabriel, Alda Marques, Daniela Figueiredo
Journal: European Respiratory Journal (2011)

Background:  The World Health Organization has emphasised the need for a patient-centred health care for the management of chronic conditions. COPD is a highly incapacitating chronic disease and its non-pharmacological management has been based on pulmonary rehabilitation programs. However, patients9 perspectives regarding their own concerns have received little attention from these programs, which is crucial to design adequate patient-centred interventions.   Aims and objectives:  This study aimed to identify the concerns and fears of patients with moderate-to-very severe COPD, regarding their actual and future condition.   Methods:  A qualitative, cross-sectional study was carried out with 18 COPD outpatients. Data were collected using audiotaped semi-structured interviews to capture patients9 detailed perceptions. A thematic analysis was performed by 2 independent judges.   Results:  Participants were mostly male (n=11; 61.1%), with a mean age of 58.4 (SD=8.3) years old and a mean FEV 1  percentage predicted of 43.1 (SD=17.7)%. Patients were mainly concerned about the progression of their condition (n=10; 55.5%) associated with the deterioration of their physical capacities (n=5; 27.8%) and becoming older (n=3; 16.7%). Fears about being on their own (n=3; 16.7%) and dying due to their respiratory disease (n=9; 50%), particularly dying of asphyxiation (n= 6; 33.3%), were also reported by patients.   Conclusions:  The findings suggest that patients with COPD have significant concerns and fears about the irreversible process of their disease. Adequate knowledge about these aspects will allow health professionals to adjust pulmonary rehabilitation programs considering the patients9 emotional needs.
Tumor-Specific Idiotype Vaccines in the Treatment of Patients With B-Cell Lymphoma — Long-Term Results of a Clinical Trial
Authors: Frank J. Hsu, Clemens B. Caspar, Debra Czerwinski, Larry W. Kwak, Tina Marie Liles, Athanasia Syrengelas, Behnaz Taidi-Laskowski, Ronald Levy
Journal: Blood (1997)
Treatment of lithium tremor with metoprolol
Authors: N S Gaby, D S Lefkowitz, J R Israel
Journal: American Journal of Psychiatry (1983)

Two patients with bipolar affective disorder and a history of bronchospastic phenomena experienced tremor during lithium carbonate therapy. In both, metoprolol produced objective and subjective improvement of the tremor without producing bronchospasm. Objective improvement of tremor after use of metoprolol was documented by accelerometry. The authors discuss the implications of these findings.
Improvement in skeletal muscle dysfunction after twice-weekly exercise training in COPD patients
Authors: Fabricio Zambom, Pilar Cabollero, Maria Hernández, Esteban Gorostiaga, Javier Ibañez, Javier Hueto, José Antonio Cascante, M. Milagros Antόn
Journal: European Respiratory Journal (2011)

Introduction: Skeletal muscle dysfunction is one of the extrapulmonary effects in patients with COPD, resulting in reduced peripheral muscle strength and functional capacity and have been associated to increased mortality risk. It is unknown the optimal frequency of exercise training to optimize the effectiveness of rehabilitation.

Aim: To compare the effects of the 12-wk training period of low-volume frequency on maximal strength and muscle power.

Methods: Thirty-six moderate to severe COPD men were divided into resistance group (RG, n=14), combined group (REG, n=14) and control (COG, n=8).RG and REG performed a low volume exercise training for 12 weeks. The subjects were tested for maximal strength in the leg press (1RMLP), lower limb power at 70%1RM (PO70%LP), maximal strength in chest press (1RMCP) and seated row (1RMSR). Statistical analyses were performed with SPSS.

Results: 1RMLP increased 26% (from 189±52 to 238±68kg, P<0.001) in REG, 33% (from 189±56 to 250±89kg, P<0.001) in RG and was higher (P<0.05) than in the CG. 1RMCP increased 31% (from 50±12 to 66±18kg, P<0.001) in RG, 35% (from 51±17 to 67±17kg,P<0.001) in REG and was higher (P<0.001) than in CG. 1RMSR increased (P<0.001) 31% in REG and 41% in RG compared to CG. PO70%LP increased 50% (from 557±290 to 725±258 w, P<0.001) in REG, 33% (from 601±167 to 797±212 w, P<0.001) in RG.

Conclusions: Twice-weekly resistance exercise improves lower and upper body maximal strength and lower muscle power in COPD. Once-weekly resistance training is as effective in eliciting improvements in maximal strength and muscle power as twice-weekly resistance training.

Supported by Ministry of Education of Spain and Health Department of Navarre
Blockade of TSLP pathway alters asthma biomarkers
Authors: Jeannette Bigler, Michael Boedigheimer, Kevin Gorski, Paul O'Byrne, Ying Wang, Gail Gauvreau, Louis-Philippe Boulet, Donald Cockcroft, Mark FitzGerald, Beth Davis, Clapton Dias, Lynn Smith, Edgar Bautista, Richard Leigh, Andrew Welcher, Jane Parnes
Journal: European Respiratory Journal (2014)

Thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine produced in response to pro-inflammatory stimuli, drives allergic inflammatory responses mostly through its effect on dendritic and mast cells. TSLP reportedly is increased in the airways of asthmatic subjects. AMG 157 is a human anti-TSLP monoclonal antibody that blocks interaction between TSLP and its receptor.  The goal of this study was to evaluate AMG 157 effects on asthma biomarkers in mild atopic asthmatic subjects after an inhaled allergen challenge.  The study consisted of 31 subjects who received three doses, at monthly intervals, of 700mg AMG 157 (n=16) or placebo (n=15). Allergen challenges were performed pre-dose, and 6 and 12 weeks after initiation of dosing. Sputum eosinophil counts, blood mRNA and fractional exhaled nitric oxide (FeNO) were collected before and after allergen challenge and blood eosinophil counts and Th2/Th1 ratio were followed prior to allergen challenge through the treatment period.  AMG 157 attenuated allergen-induced airway responses. Pre-allergen FeNO and blood and sputum eosinophil counts decreased significantly with AMG 157. In whole blood transcript analysis, genes highly expressed in eosinophils were elevated after allergen challenge. Pre-dose gene expression and eosinophil count were well-correlated. However, no AMG 157 effects on blood transcript profiles were detected. Treatment with AMG 157 was associated with a decreased Th2/Th1 cell ratio, driven mostly by a decrease in Th2 cells.  The reduction in these markers of airway and systemic inflammation in AMG 157-treated subjects supports a role of TSLP in allergen-induced responses in patients with allergic asthma.
Pulmonary artery diameter and pulsatility did not decrease after vasodilator therapy lasting two years
Authors: Pierluigi Bracciale, Fabio Valerio, Salvatore Bellanova, Giuseppe Valerio, Liliana Mangiacotti, Anna Grazia D'Agostino
Journal: European Respiratory Journal (2011)

Background: In Pulmonary Hypertension (PH) the Pulmonary Artery (PA) dilates proportionally with pulmonary artery mean pressure (PAPx) and resistance (PVR) together with a reduced pulsatility.

Aim of the study: Our aim was to assess effect of vasodilator therapy (eg Bosentan) upon diameter and pulsatility of PA during PH.

Methods: Twenty patients affected by PH were studied by means of whole body pletismography, haemodynamics, and HRCT. Bosentan (125mg bid) was administered for two years and examination were repeated again on 10 patients still alive.

Results: In survivors Bosentan diminished pulmonary artery pressure and vascular resistance; pulmonary artery diameter and pulsatility did not change significantly with a modest worsening.

Conclusion: The lack of changes of diameter, despite the decrease of pressures, indicate that progressive intrinsic wall vessel changes took place. Pulmonary artery diameter and pulsatility do not allow to assess the response to the therapy.
A pharmacokinetic comparison of the Marqibo 3 and 5 vial injection kits in metatastic melanoma patients
Authors: P. Hwu, N. Papadopoulos, K. Kim, A. G. Vardeleon, S. Campbell, R. Namdari, G. Choy, G. Berk, A. Bedikian
Journal: Journal of Clinical Oncology (2007)

8575 Background: In nonclinical and clinical studies, liposomal encapsulation of vincristine sulfate (VCR) increased the circulation time and accumulation of VCR at the tumor site, and thus improved antitumor efficacy in comparison to VCR. Marqibo (vincristine sulfate liposomes injection) may be administered safely at doses exceeding that typically employed by VCR, with a manageable pattern of clinical toxicities consistent with VCR. Methods: We conducted a phase I, single-center, open-label, randomized, 2-arm crossover study designed to compare the pharmacokinetics (PK) of Marqibo utilizing the 3- and 5-vial kits administered 2 mg/m 2 IV infusion once every 2 weeks in histologically confirmed, surgically nonresectable Stage III or IV metastatic cutaneous, mucosal, or choroidal melanoma patients. Patients randomized to receive the 3-vial kit at Cycle 1 were crossed over to receive the 5-vial kit at Cycle 2 or vice versa. The 3-vial kit was used for all patients at all cycles from Cycle 3 to end of treatment. Antitumor activity was assessed by CT scan every 4 cycles. Blood samples for PK analysis was collected at pretreatment, during infusion, end of infusion, and at various time points within 96 hours post end of infusion at Cycles 1 and 2. Total VCR concentration and released vincristine concentration was measured using HPLC-MS/MS method. Results: Fifteen patients were enrolled and treated; 11 were evaluable for the PK analysis. Median number of cycles received was 4 (1- 24). Objective response was observed in 13% (1 CR, 1 PR) or stable disease (20%, 3 SD) as their best response. The 90% CI (0.83–1.12) on the ratio of the means of the AUC 0-inf of the 3- and 5-vial kits was within the interval of 0.80–1.25 confirming the bioequivalence of the two kits. Seventy-three percent discontinued treatment due to disease progression and 13% discontinued due to adverse events. Adverse events included hypoesthesia or paresthesia, constipation, numbness, weakness, fatigue, nausea, vomiting. Conclusions: Single agent Marqibo demonstrated moderate activity in advanced Stage IV melanoma patients and was generally well tolerated with similar adverse event profile to VCR. The 3- and 5-vial kits produced similar bioequivalent PK profiles. No significant financial relationships to disclose.
Clinical profile and treatment of elderly patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease. A comparative syudy
Authors: Hajer Benabdelghaffar, Othmen Neffati, Soraya Fenniche, Ines Akrout, Dorra Greb, Leila Fekih, Hela Hassene, Tawadoud Khmiss, Dalinda Belhabib, Mohamed Lamine Megdiche
Journal: European Respiratory Journal (2013)

Hospitalizations for chronic obstructive pulmonary disease (COPD) occur mostly in elderly patients. We describe the characteristics of elderly patients hospitalized for exacerbation of COPD in a pulmonary service, compared with the younger age group. The aim was to examine if the advanced age increases the frequency, duration and severity of ECOPD. Patients with COPD were prospectively enrolled and followed between January 2007 and December 2012. Patients were divided in two groups; A total of 100 patients were recruited among them 50 were more than 70 years. We compared the differences between the 2 groups and the rest regarding comorbidity, severity of COPD, previous admissions, length of stay and treatment prescribed. Comorbidity was assessed by the Charlson index. The elderly patients had more severe COPD (P =0.02) and had a lower body mass index (P =0.05), elderly patients had greater presence of arrhythmias and left ventricular hypertrophy (P = 0.01) and received more diuretics (P
Improved survival for children with B-cell acute lymphoblastic leukemia and stage IV small noncleaved-cell lymphoma: a pediatric oncology group study.
Authors: W P Bowman, J J Shuster, B Cook, T Griffin, F Behm, J Pullen, M Link, D Head, A Carroll, C Berard, S Murphy
Journal: Journal of Clinical Oncology (1996)

PURPOSE In an effort to improve outcome for children with advanced B-cell malignancies, a treatment plan based on a published regimen that consists of four courses of fractionated cyclophosphamide (cyclo) given with doxorubicin (doxo) and vincristine (VCR) was intensified by alternating with sequential high-dose methotrexate (MTX) and cytarabine (Ara-C), given in conjunction with intrathecal (IT) MTX and Ara-C. PATIENTS AND METHODS From October 1986 to October 1992, 133 eligible patients were enrolled: 74 with B-cell (surface immunoglobulin-positive [Slg+] acute lymphoblastic leukemia (B-ALL) and 59 with stage IV small noncleaved-cell lymphoma (SNCCL). The median age was 8 years; there were 103 males and 30 females. Abdominal tumor masses were prominent in 63 cases (33 B-ALL and 30 stage IV SNCCL). RESULTS Complete remission (CR) was achieved in 66 B-ALL and 57 stage IV patients (93% overall). At 4 years, the estimated event-free survival (EFS) rate is 65% +/- 8% for patients with B-ALL and 79% +/- 9% for those with stage IV SNCCL. Among patients with CNS involvement, 23 of 36 remain in CR (4-year EFS rate, 64% +/- 13%). Relapses occurred early; only 3 patients relapsed after completion of therapy. Thirteen relapses occurred in the marrow, three in the CNS, and six in other sites. Of 11 CNS-positive patients who relapsed, only two recurred primarily in the CNS. CONCLUSION The results of this study indicate that with intensified chemotherapy an increasing potential for cure exists for patients with B-ALL and stage IV SNCCL.
Feasibility of commercial interferon-γ-based methods for the diagnosis of latent Mycobacterium tuberculosis infection in Finland, a country of low incidence and high bacille Calmette-Guerin vaccination coverage
Authors: T. Tuuminen, S. Sorva, K. Liippo, T. Vasankari, H. Soini, B. Eriksén-Neuman, A. Miettinen, I.J. Seppälä
Journal: Clinical Microbiology and Infection (2007)