tbuckley/cabot-search huggingface dataset:
Management of chronic obstructive pulmonary disease
Authors: B R. O'Driscoll
Journal: BMJ (2003)

Editor—The editorial by Babu and Chauhan on the management of acute exacerbations of chronic obstructive pulmonary disease contains a serious error of fact. The Cochrane review by Barr et al is quoted to support their proposal that standard treatment for exacerbations of chronic obstructive pulmonary disease should include theophyllines.1 This review said no such thing.

The reviewers' conclusions were that there is no evidence to support the routine use of methyl-xanthines for exacerbations of chronic obstructive pulmonary disease. Methyl-xanthines do not appreciably improve forced expiratory volume in one second (FEV1) during exacerbations, and cause adverse effects; evidence of their effect on admissions is limited.2

Although theophyllines were used by previous generations of doctors for managing acute exacerbations of asthma and chronic obstructive pulmonary disease, this use was not evidence based, and these agents have been shown to be associated with increased adverse effects (but no proved clinical benefit) for both groups of diseases.2,3 I have occasionally had to deal with severe adverse effects (including cardiac arrest) when intravenous aminophylline had been given to patients with acute airflow obstruction by admitting medical teams, especially when strict safety precautions were not followed.

This misleading statement in a BMJ editorial could lead a new generation of doctors on call to restart the use of these toxic drugs, which are of unproved clinical benefit when given in addition to more modern treatment. This error of fact will require a prominent notice of correction in the journal.
Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial
Authors: C. C McDonald, F. E Alexander, B. W Whyte, A P. Forrest, H. J Stewart
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To determine any cardiac or vascular morbidity associated with long term treatment with tamoxifen given after mastectomy for primary breast cancer. <b>Design</b>: Cohort study using linkage between database of a randomised trial and statistics of Scottish hospital inpatients to identify episodes of cardiac and vascular morbidity. <b>Setting</b>: NHS hospitals in Scotland. <b>Subjects</b>: 1312 women who had undergone mastectomy for breast cancer and who were randomised either to a treatment group to receive adjuvant tamoxifen or to a control group to be given tamoxifen only on first relapse of disease. Maximum duration of tamoxifen treatment was 14 years. Total woman years of follow up were 9943. <b>Main outcome measures</b>: Randomised and observational comparisons of risk (expressed as hazard ratios) of myocardial infarction, other cardiac event, cerebrovascular disease, or thromboembolic event according to treatment allocated and between non-users, former users, and current users of tamoxifen. <b>Results</b>: Use of tamoxifen was associated with lower rates of myocardial infarction. Hazard ratio for women in control group was 1.92 (95% confidence interval 0.99 to 3.73) compared with women allocated to adjuvant treatment. The association was stronger for current use: hazard ratio for non-users was 3.49 (1.52 to 8.03) compared with current users. Current users of tamoxifen, however, had higher rates of thromboembolic events: hazard ratio for non-users was 0.40 (0.18 to 0.90) compared with current users. <b>Conclusions</b>: Our results provide further evidence that tamoxifen reduces the risk of myocardial infarction. Thromboembolic events should be carefully monitored in trials of tamoxifen, particularly those of prophylactic treatment, in which tamoxifen is given to healthy women.
Risk-factors for the acquisition of imipenem-resistant Acinetobacter baumannii in Spain: a nationwide study
Authors: J.M. Cisneros, J. Rodríguez-Baño, F. Fernández-Cuenca, A. Ribera, J. Vila, A. Pascual, L. Martínez-Martínez, G. Bou, J. Pachón
Journal: Clinical Microbiology and Infection (2005)
Burden of serious fungal infections in Spain
Authors: J.L. Rodriguez-Tudela, A. Alastruey-Izquierdo, S. Gago, M. Cuenca-Estrella, C. León, J.M. Miro, A. Nuñez Boluda, I. Ruiz Camps, A. Sole, D.W. Denning
Journal: Clinical Microbiology and Infection (2014)
Borderline personality disorder, boundary violations, and patient- therapist sex: medicolegal pitfalls
Authors: T G Gutheil
Journal: American Journal of Psychiatry (1989)

The author addresses the issue of sexual relations between therapist and patient and the related boundary violations that are involved in such relations. He points out that patients with borderline personality disorder are particularly likely to evoke boundary violations, including sexual acting out. These patients apparently constitute the majority of patients who falsely accuse therapists of sexual involvement. Therapists who are aware of patterns of errors in therapy and countertransference--through education, anticipation, and forewarning--can avert the serious outcomes that result from these errors.
Abstract 5554: FoxO1 Stimulates Autophagic Flux Through Upregulation of the Small GTP Binding Protein Rab7
Authors: Nirmala Hariharan, Junichi Sadoshima
Journal: Circulation (2009)

We have shown previously that FoxO1, a member of the FoxO transcription factor family, is upregulated by nutrient starvation and cardiac unloading. FoxO1 in turn promotes autophagy, thereby mediating survival and regression of hypertrophy in cardiac myocytes. The current investigation addressed the molecular mechanism by which FoxO1 promotes autophagy in cardiac myocytes. In order to evaluate formation of both autophagosomes and autolysosomes, cultured cardiac myocytes were transduced with adenovirus harboring mRFP-GFP-LC3. Adenoviral mediated overexpression of FoxO1 increased accumulation of both GFP-LC3 dots (1.5 fold vs Ad-LacZ) and mRFP-LC3 dots (2 fold vs Ad-LacZ, p&lt;0.01), which was further enhanced in the presence of protease inhibitors(PI) (1.5 fold vs Ad-LacZ+PI, p&lt;0.01). FoxO1 overexpression caused greater increases in mRFP-LC3 dots than GFP-LC3 dots, suggesting that FoxO1 enhances autolysosome formation more strongly than autophagosome formation, thereby stimulating autophagic flux. Rab7 is a small GTP binding protein which plays an important role in mediating maturation of late autophagic vacuoles. mRNA expression of Rab7 is strongly upregulated in cardiac myocytes (4.7 fold, p&lt;0.05) and hearts (2.5 fold) with FoxO1 overexpression. Overexpression of Rab7 was sufficient to stimulate autolysosome formation and autophagic flux in cultured cardiac myocytes, as evidenced by accumulation of LC3-II (2.8 fold, p&lt;0.05) and mRFP-LC3 dots (2.3 fold, p&lt;0.05), and decreased p62 (−40%, p&lt;0.05). Lentivirus mediated knockdown of Rab7 (LV-sh-Rab7) attenuated FoxO1- induced autophagy, as indicated by LC3-II accumulation (Ad-Foxo1WT 1.9, Ad-Foxo1WT + LV-sh-Rab7 0.11 vs Ad-LacZ, p&lt;0.05) and p62 expression levels (Ad-Foxo1WT 0.49, Ad-Foxo1WT + LV-sh-Rab7 0.84 vs Ad-LacZ, p&lt;0.05), suggesting that Rab7 mediates FoxO1-induced autophagy in cardiac myocytes. In summary, FoxO1 stimulates autophagosome/autolysosome formation and autophagic flux in cardiac mycoytes, accompanied by upregulation of Rab7. Rab7 plays an essential role in mediating FoxO1-induced stimulation of autophagy, possibly by stimulating autophagosome -lysosomal fusion in cardiac myocytes.
Role of daunorubicin in the induction therapy for adult acute myeloid leukemia.
Authors: N Usui, N Dobashi, T Kobayashi, S Yano, N Maki, O Asai, T Saito, Y Yamaguchi, H Watanabe, A Kato, A Ogihara, M Katori, M Nagamine, Y Takei, H Yamazaki, S Funakoshi, N Tajima, M Ogawa, Y Kuraishi
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the relationship of total-dose of daunorubicin (DNR) to the induction therapy and treatment outcome, we have administered individualized doses of DNR during induction treatment to patients with acute myelogenous leukemia (AML). PATIENTS AND METHODS Ninety-two previously untreated adult patients with AML who entered our hospital were analyzed for the dose of DNR required to achieve complete remission (CR), the CR rate, disease-free survival (DFS), and overall survival (OS). Induction therapy consisted of DNR 40 mg/m2 daily intravenously from day 1 until the marrow was hypoplastic, cytarabine (Ara-C), prednisolone (PRD), and/or 6-thioguanine (6-TG). RESULTS Eighty-three of 92 patients with adult AML were assessable for this study. Sixty-three (76%) patients achieved CR. Fifty-two of 63 CR patients achieved the CR in the first course of induction therapy, and 11 patients required the second course of induction therapy. The 5-year and 10-year DFS rates were 31.2% and 5-year and 10-year OS rates were 45.1% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120 to 480 mg/m2). DNR dose did not influence the response to therapy and was not influenced by the initial WBC count or French-American-British (FAB) system classification. CONCLUSION These results indicated that when the dose was linked to observed tumor response, the optimal dose of DNR in the induction therapy was approximately 280 mg/m2 (40 mg/m2 for 7 days), which is greater than the conventional dose of 40 to 60 mg/m2 for 3 days.
Late-breaking abstract: Pre-clinical characterization of RP3128, a novel and potent CRAC channel inhibitor for the treatment of respiratory disorders
Authors: Kasiviswanath Routhu, Meyyappan Muthuppalaniappan, Gayatriswaroop Merikapudi, Kanthikiran Varanasi, Sridhar Veeraraghavan, Srikant Viswanadha, Swaroop Vakkalanka
Journal: European Respiratory Journal (2011)

Introduction:  Calcium release activated calcium channels inhibitors have a potent role in treatment of autoimmune disorders mediated dysregulated T-lymphocyte and mast cell functioning. Herein, we describe the pre-clinical of RP3128, a novel and potent CRAC channel inhibitor with scope for development as a clinical candidate for asthma.   Methods:  Inhibition of CRAC channel activity in Jurkat cells, cytokine release from human whole blood or PBMC, and mast cell degranulation were estimated.  In vivo  efficacy of the compound was determined in experimental models of asthma in guinea pigs including PAF or ovalbumin induced eosinophil infiltration into lungs as well as ovalbumin induced histamine release from mast cells.   Results:  RP3128 significantly inhibited calcium entry into Jurkat cells (33 nM) besides reducing IL-4 ( 70% reduction in eosinophil infiltration in an acute model of PAF-induced allergic asthma as well as in an experimental model of ovalbumin-induced chronic airway inflammation. Consistent with  in vitro  findings, the compound caused a significant inhibition of mast cell degranulation manifested by a reduction in histamine release.   Conclusions:  Results demonstrate the potential of RP3128 as an antiasthmatic agent as evidenced from pre-clinical data. Further biological profiling in respiratory models is planned in addition to toxicological evaluation prior to Phase 1 clinical trials.
Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia.
Authors: M J Keating, H Kantarjian, S O'Brien, C Koller, M Talpaz, J Schachner, C C Childs, E J Freireich, K B McCredie
Journal: Journal of Clinical Oncology (1991)

Thirty-three patients with chronic lymphocytic leukemia (CLL) with advanced Rai stage (III-IV) or progressive Rai stage (0-II) disease were treated with fludarabine as a single agent. Eleven patients (33%) obtained a complete remission (CR), 13 (39%) a clinical CR with residual nodules as the only evidence of disease (nodular partial remission [PR]), and two patients (6%) achieved a PR for a total response rate of 79%. Response was rapid, usually occurring after three to six courses of treatment. The major morbidity was infection. Febrile episodes occurred in 13% of the courses (pneumonia 6%, minor infection 4%, and transient fever of undocumented cause 3%). Fludarabine appears to be the most cytoreductive single agent so far studied in CLL.
The evaluation of the influence of occupational and non-occupational factors on the development of occupational COPD
Authors: Nailya Mazitova, Anatoly Saveliev, Julia Galiullina, Aigul Ziganshina, Zuhra Berheeva, Nail Amirov
Journal: European Respiratory Journal (2011)

Occupational exposure is a known risk factor for chronic obstructive pulmonary disease (COPD). However the contribution of occupational exposure and smoking to COPD development has not yet been quantified.

Aims and objectives: The aims of this study were to ascertain the prevalence of COPD among industrial workers and to establish the relative contributions of smoking and occupational factors.

Methods: A cross-sectional study of 1,397 randomly selected industrial workers has been conducted. Among them, 625 had occupational exposure to vapor, gas, dust or fumes (VGDF). Baseline spirometry was performed for all the participants. Those with airflow limitation (FEV1/FVC <0.70) were examined by post-bronchodilator test. All the participants answered to questionnaire included the information on occupational history, respiratory symptoms and smoking habits.

Results: The overall prevalence of COPD was 7.5%, the odds ratio (OR) of occupational COPD development was 5.8 (95%CI 3.5-9.5; p<0.0001) with PAR%=20.3. Analysis of linear predictors in regression model showed that the effect of smoking on the COPD development ranges from 5 to 40% depending on other factor values. Meanwhile, the contribution of occupational factors in the development of COPD monotonously and significantly (p<0.0001) increased with the growth of WGDF levels: OR was from 1.8 (95%CI 0.9-3.5) to 28.4 (95%CI 13.8-58.6), PAR% from 1.2 to 28.8.

Conclusions: Smoking and VGDF are interacting factors and their influence can be considered as comparable under certain conditions. Thus, the prevention of COPD should include not only smoking cessation, but also reducing the levels of the occupational factors.
Exertional Leg Pain in Familial Mediterranean Fever: A Manifestation of an Underlying Enthesopathy and a Marker of More Severe Disease
Authors: Iris Eshed, Yossi Rosman, Avi Livneh, Ron Kedem, Pnina Langevitz, Ilan Ben‐Zvi, Merav Lidar
Journal: Arthritis & Rheumatology (2014)

Exertional leg pain is a characteristic musculoskeletal manifestation of familial Mediterranean fever (FMF). We aimed to define the frequency and characteristics of exertional leg pain in a large cohort of FMF patients and to evaluate for additional signs and symptoms of spondyloarthritis (SpA) in this patient population. FMF patients were allocated into study or control groups based on the presence or absence of exertional leg pain. Randomly selected patients underwent magnetic resonance imaging (MRI) of the ankle as well as plain radiography of the sacroiliac joints. The prevalence of exertional leg pain among the 170 FMF patients included in the study was 58.2%. Patients with exertional leg pain had significantly more joint attacks (74.7% versus 40.8%; P < 0.0001), fever attacks (35.4% versus 15.5%; P = 0.004), and pleuritis attacks (48.5% versus 29.6%; P = 0.013) as well as more attacks per year. Elevations of inflammation markers were significantly more frequent among the study group (for the erythrocyte sedimentation rate, 44.4% of patients versus 21.1% of patients; P = 0.016) (for the C-reactive protein level, 48.4% of patients versus 31.8% of patients; P = 0.013), and M694V homozygosity was more prevalent among the study group (45.5% versus 21.1%; P = 0.001). Signs compatible with enthesopathy on MRI were observed in 73.5% of patients in the study group and in 33.3% of patients in the control group (P = 0.046). Definite SpA was diagnosed in 41.2% of the patients in the study group compared to none of the controls (P = 0.07) (odds ratio 1.7 [95% confidence interval 1.2-2.3]). Exertional leg pain is a common manifestation of FMF and is a marker of a more severe disease phenotype. Additionally, exertional leg pain is frequently associated with sacroiliitis and an underlying ankle enthesopathy and should therefore be considered a new feature of SpA.
CSE exposure abrogates regulatory effects of the bronchial epithelium on B cell survival and IgA production in a coculture system. A pivotal role of TACI
Authors: Maha Zohra Ladjemi, Bruno Detry, Marylène Lecocq, Yves Sibille, Charles Pilette
Journal: European Respiratory Journal (2012)

Background:  Chronic obstructive pulmonary disease (COPD) is associated with chronic airway inflammation and structural remodelling, in particular of the epithelium, which is impaired in its capacity to transport immunoglobulin (Ig) A. Although COPD is mostly related to cigarette smoking, only a minority of smokers develops this disease and factors of cigarette exposure susceptibility remain not clear. Even though peribronchial lymphoid follicles have been described in severe COPD, it remains unknown whether B-cell conditioning is altered in this disease, especially after CSE (Cigarette Smoke Extract) exposure.  Objectives:  In this study, we report on CSE exposure data using a coculture model of B cells with human primary bronchial epithelium (re)differentiated in vitro in air-liquid interface.  Methods:  IgA synthesis was studied following CSE exposure in CD19+ B cells (purified by immunomagnetic sorting from healthy blood donors) after co-culture for 13 days with a bronchial epithelium from severe COPD patients. B cells were also assessed by flow cytometry for cell activation and survival.  Results : In four independent experiments, we observed that IgA production and cell survival were upregulated in B cells cocultured with the bronchial epithelium, as compared to B cells cultured alone. CSE exposure of the epithelium abrogated these effects, and this was associated with the suppression of TACI induction upon co-culture.  Conclusion : These data suggest that a crosstalk exists between B cells and the epithelium with respect to COPD, which could be mediated at least in part through regulation of TACI.
Effect of critical care-trained dedicated medical leadership on the delays at acute noninvasive ventilation (NIV) set ups at the "front door"
Authors: Sukhneet Randhawa, Helena Boryslawskyj, Natasha Santana-Vaz, Ben Beauchamp, Biman Chakraborty, Pooja Sharma, Jumaa Bwika, Rahul Mukherjee
Journal: European Respiratory Journal (2014)

Introduction   NIV is the first-line treatment for patients with acute hypercapnic respiratory failure (NIV should be “considered for all patients with a persisting respiratory acidosis after a maximum of one hour of standard medical therapy”,  Royal College of Physicians,  October 2008). We compare the time from initial admission to NIV mask application at two acute hospitals in central England: an NIV service in a 709-bedded hospital (Hospital 1) which appointed a Lead consultant in 2009 as per BTS recommendations and another similar NIV service without a medical lead at a 521-bedded hospital (Hospital 2).   Methods   Data from Hospital 1 taken from an acute NIV database maintained continuously since 2004; Data from Hospital 2 were drawn from NIV physiotherapy records. All patients during a 6-month period between 01/10/2010-01/04/2011 and 01/10/2011-01/04/2012 were included: 458 acute NIV episodes (9 excluded due to incomplete data).   Results   In the 2011/2012 period, 82.0% of patients at Hospital 1 received NIV within 3 hours with 69.49% of patients receiving NIV within 3 hours at Hospital 2. Hospital 1 performed similar to Hospital 2 in 2010/2011 but better in 2011/2012 compared with Hospital 2 not only in 9% receiving NIV within 3 hours9 but also in significantly reducing variance with a peak very close to 1 hour.   Conclusions   The service at Hospital 2 did not show any measurable improvement between 2010/2011 and 2011/2012. As demographics were very similar and the NIV physiotherapy service common to both, this difference could be a reflection on the medical leadership of the NIV service at Hospital 1 as per BTS recommendations.
gamma-c gene transfer into SCID X1 patients' B-cell lines restores normal high-affinity interleukin-2 receptor expression and function
Authors: H Hacein-Bey, M Cavazzana-Calvo, F Le Deist, A Dautry-Varsat, C Hivroz, I Riviere, O Danos, JM Heard, K Sugamura, A Fischer, G De Saint Basile
Journal: Blood (1996)
Focus on prevention and treatment of obstructive sleep disordered breathing in childhood
Authors: Athanasios Kaditis, Patrick Lévy
Journal: European Respiratory Journal (2015)

In this issue of the European Respiratory Journal , treatment outcomes of obstructive sleep apnoea syndrome (OSAS) in obese community-dwelling children are reported by Alonso-Álvarez et al. [1]. The results of the NANOS multicentre trial indicate that obese children have a high rate of persistent disease despite treatment with adenotonsillectomy, nutritional interventions or even nasal continuous positive airway pressure (CPAP). OSAS is the most severe form of obstructive sleep disordered breathing (SDB), which is a syndrome of upper airway dysfunction during sleep characterised by snoring and increased respiratory effort [2, 3]. A combination of one or more anomalies, such as adenotonsillar tissue hypertrophy, obesity, subtle or syndromic craniofacial abnormalities, or neuromuscular disease, contributes to increased upper airway resistance and pharyngeal collapsibility, predisposing to intermittent upper airway obstruction during REM and NREM2 sleep [2]. Successful management of OSAS in obese children requires a combination of treatment modalities <http://ow.ly/PkPf3>
Aerodynamic characteristics of dry powder inhaler (DPI) single-dose combination of budesonide with formoterol in vitro study validation
Authors: Ana Luisa Fernandes, Marina Andrade Lima, Luiz F.F. Pereira
Journal: European Respiratory Journal (2012)

Background : The aerodynamic properties of dry powder inhalers are essential for drug efficacy. Despite the availability of several devices, few studies have measured aerodynamic characteristics of the drug delivery using their proper device.  Aim:  To describe the aerodynamic characteristics of the combination dry powder inhaler (DPI) Alenia® single-dose AeroCaps®(AA), which contains budesonide (BUD) and formoterol fumarate (FF) when compared with Foraseq® Aerolizer®(FA) as the reference combination drug.  Methods:  They were assessed using quantitative sample analysis by high pressure liquid chromatography (HPLC), dose uniformity sampling apparatus (DUSA) and Andersen cascade impactor (ACI) to confirm the presence of active ingredients as well as the uniformity of released dose and the aerodynamic diameter of particles produced by their proper devices.  Results:  Table 1 summarize the experiments.  Alenia showed microbial quality control within acceptable Conclusions:  Alenia® and Foraseq® had active ingredients, dose uniformity and appropriate aerodynamic diameter to their respective dry powder inhalers.  Funded by Ache Laboratorios.
Focus: Washington: "A little of the Buchenwald touch"
Authors: J Roberts
Journal: BMJ (1994)

Hazel O'Leary is the daughter of two doctors, and she says she grew up learning that ill patients must understand the “potential horrors” of every lifesaving procedure. She is the widow of a man whose life was extended as a direct result of cancer research. And she is President Clinton's secretary of energy.

In December Mrs O'Leary began to hear of experiments begun in the late 1940s that subjected Americans to radiation without their knowledge. Such research, if carried out as so far reported, was in clear conflict with the Nuremberg Code, which declares that “the voluntary consent of a human subject is essential” to morally acceptable research. The code,of course, was written after Nazi researchers were found to have carried out abominable experiments on prisoners in concentration camps. And even by 1950 …