tbuckley/cabot-search huggingface dataset:
Combined COPD assessment using the new GOLD guidelines
Authors: Alex Mackay, Gavin Donaldson, Anant Patel, Richa Singh, John Hurst, Jadwiga Wedzicha
Journal: European Respiratory Journal (2012)

GOLD guidelines advocate symptomatic assessment using the CAT or mMRC, followed by spirometry and/or exacerbation history to determine exacerbation risk (fig 1). We examined this guidance in the London COPD cohort.

![Figure][1] 



106 patients completed daily symptom diary cards for ≥1 year and the CAT at least once when stable. All exacerbations received additional systemic and/or inhaled therapy.

Mean age was 72.6 years (SD 8.3), FEV1 1.1L (0.5), and FEV1 predicted 48.5% (16.4).

![Figure][1] 



Using CAT and GOLD grade to assess exacerbation risk yielded significantly more high risk patients (category C&D) than when exacerbation history was used (56.6% vs. 33.0%, p=0.001).

After combined assessment using both GOLD grade and exacerbation history, few patients were included in the high risk, less symptoms category C: 8.5% (9/106) using CAT and 10.4% (11/106) using mMRC.

In a specialist outpatient setting, few patients fulfil criteria for inclusion in the high risk, less symptoms category C. Furthermore, the method chosen to assess exacerbation risk had a large influence on risk stratification. Additional work is required to examine the utility of this aspect of GOLD guidance in primary care to screen for exacerbation risk.

 [1]: pending:yes
Study of pulmonary embolism prevalence depending on age and sex by autopsy data
Authors: Nataliia Tsymbalyuk, Yuriy Mostovoy, Nataliia Slepchenko
Journal: European Respiratory Journal (2012)

Background. Pulmonary embolism (PE) is the third most frequent cause of death after ischemic heart disease and stroke. Problems concerning statistic data as for PE and the dynamics of its prevalence are insufficient in Ukraine.  Aims and objectives. To study the dynamics of PE prevalence depending on age and sex, to determine factors leading to fatal outcome between 1993 and 2002 years by the results of autopsies.  Methods. To determine the dynamics of prevalence and causes of fatal PE development we undertook a retrospective analysis of 2260 case reports of patients who died during 1993-2002 years.  Results. The results of 2260 autopsies done during the period of 1993-2002 showed that PE in the structure of pathologic diagnosis occurred in 121 cases (5.3%), mean time of development of PE symptoms was 6.3±2.3 days. 65 of them were males (53.7%) and 56 - females (46.3%) with average age 64.1±2.3 years. The dynamics of PE prevalence as a cause of death in patients during the study period tended to increase ranging from 3.3% to 12.2%; the average prevalence rate of pulmonary embolism for ten years of study being 5.3%. Oncologic diseases (53.9%), deep vein thrombosis of lower extremities (23.1%) and ischemic heart disease (19.0%) were the major etiological factors causing the development of fatal symptoms of PE in patients during the last decade.  Conclusions. Individuals suffering from deep vein thrombosis, ischemic heart disease with atrial fibrillation and those undergoing operations for oncologic diseases are at great risk of PE development. If sudden dyspnea, chest pain and decrease of blood pressure appear in the patients of risk group additional methods of examination should be used to exclude PE.
When needed use of inhaled steroids in children with asthma
Authors: Walid Tarsin, Sondos Eddali, Ali Mugadami
Journal: European Respiratory Journal (2014)

Asthma attacks vary in frequency and severity. Many children with asthma are symptom-free most of the time, with occasional episodes of shortness of breath and acute attacks, which may resolve rapidly after pharmacological intervention. Inhaled corticosteroids (ICS) are the most effective medicine for long-term control of asthma in most children. However, often, ICS are used intermittently by patients or recommended by physicians to be used only at the onset of exacerbations.  Asthmatic children visiting Tripoli Medical Center emergency room(ER) or their physician for follow up were investigated on the preference and the use of the ICS. 200 patients were included, their mean (SD) age was 7.1 (3.6) years. 160 patients had ER visit and 63 had hospital admission before. All patients used ICS as a routine treatment for asthma. 31.5% (n=63) used ICS regularly and 68.5% (n=137) used ICS during attacks only.  84.5% (n=169) of the total patients and 100% (n=137) of the patients taking ICS SOS get asthma exacerbation after more than 3 months if they exposed to an aggravating factor.These patients may not need to take ICS regularly. This limit the long-term exposure to ICS.  According to the Libyan culture most of the asthmatic children or their families do not like to take inhaled medication. The results of this study confirm this finding; were 68% (n=136) prefer to use oral medication than the inhaled therapy and 92% (n=184) prefer to use the ICS as SOS.
Acute effects in cough flow and chest wall volume after breath-stacking maneuver in amyotrophic lateral sclerosis (ALS)
Authors: Ana Cristina Maciel, Vanessa Resqueti, Guilherme Fregonezi, Andrea Aliverti, Íllia Nadinne Lima, Armele Dornelas de Andrade
Journal: European Respiratory Journal (2014)

Background : Amyotrophic Lateral Sclerosis (ALS) patients show decreased inspiratory muscle strength and weakness of the expiratory muscles associated with ineffective cough production. The breath-stacking maneuver (BS) increases inspired volume and may influence cough flow generation. Aim : To evaluate the effects of BS in cough flow and chest wall volume in ALS patients and healthy subjects by opto-electronic plethysmography (OEP). Methods : 22 subjects were assessed, 7 ALS subjects(4 M), (51.0 ± 14.53 years, BMI 24.57 ± 2.12 kg/m2, FVC 2.57 ± 0.93 L, FEV1/FVC 0.82 ± 0.08 L) and 15 matched healthy subjects (8M), (45.8 ± 15.5 years e BMI 25.3 ± 1.84 Kg/m2), with normal lung function. Voluntary cough flow and tidal volume of chest wall (VTCW) compartments were analyzed before and after the BS maneuver in 45o inclination position by OEP. Results : VTCW increased after the BS in both groups, ALS patients 0.35 ± 0.10 L vs 1.79 ± 1.11 L (Δ 1.44 L) and healthy subjects 0.42 ± 0.19 L vs 2.87 ± 0.64 L, (Δ 2.44 L), p < 0.0001 (two-way ANOVA). Cough flow significantly increased in both groups ALS (2.21 ± 0.71 L/s vs 3.39 ± 0.73 L/s) and healthy subjects (5.19 ± 1.28 L/s vs 6.30 ± 1.07 L/s), p < 0.001 (two-way ANOVA). Conclusion : Breath-stacking maneuver increases pulmonary volumes leading to an increase in cough flow in the 45o inclination position in both groups. Despite the smaller increase in ALS chest wall volume compared to healthy subjects, BS maneuver produced significant increase on flow cough generation, essential for the assistance of these patients.
Letter by Apostolakis et al Regarding Article, “Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation: Validation of the R <sub>2</sub> CHADS <sub>2</sub> Index in the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study Cohorts”
Authors: Stavros Apostolakis, Deirdre A. Lane, Amitava Banerjee
Journal: Circulation (2013)
Assessment for lung transplantation in cystic fibrosis
Authors: P Aurora, P Whitmore, B F Whitehead
Journal: Journal of the Royal Society of Medicine (1999)

Lung transplantation has been available as a therapeutic option for patients with end-stage cystic fibrosis (CF) lung disease from the mid-1980s. Since this time, in excess of 700 CF patients have undergone the procedure worldwide, as recipients of heart-lung, double lung, or more rarely single lung cadaveric transplants. A small number of CF patients have received living donor lobar transplants, but this procedure has been performed rarely in the UK. Survival following heart-lung or double lung cadaveric transplantation is poorer than for other solid organ transplants, with the International Registry reporting survival of 60-70% at 1 year and 30-40% at 5 years for both procedures1 (Figure 1). These survival figures vary little between major centres, and are improving only slowly. However, there is increasing evidence that correctly timed transplantation does provide patients with a significant increase in longevity, in addition to an improved quality of life2'3. As the potential benefits of the procedure become better understood, the number of potential recipients is increasingly outweighing the number of suitable donors. This has the effect of increasing waiting times for organs, with a number of patients not surviving the waiting period. This is an international problem, affecting all solid organ transplants, and is unlikely to be resolved in the near future. As post-transplant survival is relatively poor, patients must not be transplanted too early, or the potential survival benefit from the procedure is reduced. Conversely, if patients are accepted for transplantation too late, the likelihood of them receiving organs is reduced, with the assessment and acceptance for transplantation merely offering them false hope. The first goal of transplant assessment is, therefore, assessment of risk. Furthermore, if patients with particularly poor posttransplant survival potential can be identified, they can either be counselled against transplantation, or offered tailored post-transplant care in an attempt to improve their outcome. The second goal of transplant assessment is, therefore, identification of absolute and relative contraindications. ii
Efficacy and toxicity of 12 courses of ABVD chemotherapy followed by low-dose regional radiation in advanced Hodgkin's disease in children: a report from the Children's Cancer Study Group.
Authors: C J Fryer, R J Hutchinson, M Krailo, R D Collins, L S Constine, D M Hays, R M Heller, P C Davis, J Nachman, R T O'Brien
Journal: Journal of Clinical Oncology (1990)

Sixty-four patients aged 2 to 18 years with advanced-stage Hodgkin's disease (HD) were treated on a Children's Cancer Study Group (CCSG) pilot toxicity study (521-P). Therapy consisted of 12 courses of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (ABVD), followed by low-dose (2,100 cGy in 12 fractions) regional irradiation (RT). All patients were monitored for toxicity with particular attention to the pulmonary system. Six patients (9%) developed grade 3 or 4 pulmonary toxicity. Three had grade 3 toxicity based solely on changes in carbon monoxide diffusing capacity (DLCO) and remained well for more than 3 years after diagnosis. There was one fatality among the three symptomatic cases. In five cases, toxicity occurred prior to RT. One occurred after seven courses of ABVD, one after nine courses, and three after 10 courses. In one of these five cases, ABVD was stopped. The patient was given nitrogen mustard (mechlorethamine), vincristine, prednisone, and procarbazine (MOPP). This patient subsequently developed recurrence of HD and died of overwhelming sepsis. The other four continued on study and completed their chemotherapy. Three patients had no further bleomycin, and one continued bleomycin at 50% of the assigned dose. They all received mantle RT following chemotherapy, one with a boost dose to the mediastinum to 3,800 cGy and one with added RT to both lungs (1,050 cGy). In the sixth case of pulmonary toxicity, symptoms were first noticed 2 weeks after mantle RT to 3,500 cGy. This patient died of progressive respiratory failure. The event-free survival (EFS) and overall survival is 87% at 3 years. These early results indicate that this therapy is effective in advanced HD in children but has a 9% incidence of acute pulmonary toxicity.
Influence of sex and age on fluorouracil clearance.
Authors: G Milano, M C Etienne, E Cassuto-Viguier, A Thyss, J Santini, M Frenay, N Renee, M Schneider, F Demard
Journal: Journal of Clinical Oncology (1992)

Currently, fluorouracil (5-FU) is one of the major drugs used in cancer chemotherapy. Several investigators, including ourselves, have demonstrated a link between abnormalities in 5-FU clearance (Cl) and the risk of developing more or less 5-FU-related toxicities. Age and sex are among the host factors that have been implicated in the pharmacokinetic variability of drugs. Presently, no data are available on the possible influence of sex and age on 5-FU Cl.Three hundred eighty patients (mean age, 61.7 years; range, 25 to 91; 301 men and 79 women) with squamous cell carcinoma (sre) of the head and neck were treated in our institution between 1987 and 1991. 5-FU Cl was determined for a total of 1,092 chemotherapy cycles. Each cycle consisted of cisplatin and 5-day continuous intravenous infusion 5-FU (daily doses ranging between 365 and 1,224 mg/m2).5-FU Cl values (L/h/m2) showed a wide dispersion for both men (median, 179; range, 29 to 739) and women (median, 155; range, 56 to 466). 5-FU Cl values were lower significantly for women compared with men (P = .0005). When adjusted for age and dose, the influence of sex on log Cl remained significant (P = .013). There was no evidence that age modified 5-FU Cl when adjusted for sex and dose. Interestingly, for both men and women, the oldest patients (greater than 70 years) maintained their ability to clear 5-FU with daily doses that ranged from 500 to 1,000 mg/m2.These data indicate that the capacities to clear 5-FU are lower in women compared with men and are not influenced by age. It would be of interest to know whether this sex-related difference in 5-FU Cl may be clinically relevant by considering both toxicity and tumor response to 5-FU treatment.
Abstract 20131: G Protein Coupled Receptor Kinase 2 Interacting Protein 1 is a Novel Mediator Required for Retina Vasculature Development Through Notch Signaling
Authors: Jinjiang Pang, Richard Libby, Ryan Hoefen, Heidi Michaloski, Xiangbin Xu, Christine K Christie, Zhaoqiang Cui, Amy Mohan, Bradford C Berk
Journal: Circulation (2010)

G-protein-coupled receptor-kinase-2 interacting protein 1 (GIT1) is a scaffold protein. Our previous data showed GIT1 has a key role of in pulmonary vascular development by regulating VEGF mediated...
Respiratory and Limb Muscle Weakness Induced by Tumor Necrosis Factor-<b>α</b>
Authors: Michael B. Reid, Jan Lännergren, Håkan Westerblad
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The respiratory and limb skeletal muscles become weakened in sepsis, congestive heart failure, and other inflammatory diseases. A potential mediator of muscle weakness is tumor necrosis factor (TNF)-α, a cytokine that can stimulate muscle wasting and also can induce contractile dysfunction without overt catabolism. This study addressed the latter process. Murine diaphragm and limb muscle (flexor digitorum brevis [FDB]) preparations were used to determine the relative sensitivities of these muscles to TNF-α. Intact muscle fibers were isolated from FDB and microinjected with indo-1 to measure changes in sarcoplasmic calcium regulation. We found that TNF-α depressed tetanic force of the diaphragm and FDB to comparable degrees across a range of stimulus frequencies. In isolated muscle fibers, TNF-α decreased tetanic force without altering tetanic calcium transients or resting calcium levels. We conclude that (1) TNF-α compromises contractile function of diaphragm and limb muscle similarly, and (2) TNF-α decreases force by blunting the response of muscle myofilaments to calcium activation.
Radiation Therapy and Breast Cancer Risk
Authors: Andrea K. Ng, Lois B. Travis
Journal: Journal of the National Comprehensive Cancer Network (2009)

Exposure to ionizing radiation has clearly been established as one of the risk factors for the development of breast cancer. Much data on the relationship between radiation exposures and subsequent breast cancer are derived from atomic bomb survivors and women who received medical exposures either for diagnostic or therapeutic purposes. Although these populations differ in background breast cancer risks and the dose, quality, and timing of radiation, consistent findings include an increased risk with younger age at exposure, long latency to breast cancer development, and increasing risk with increasing radiation dose. Although therapeutic radiation is rarely used to treat benign conditions, it remains an important and effective treatment modality for a wide range of cancers. Increased knowledge of radiation-related breast cancer and modifying influences plays an important role in guiding the initial treatment approach for young women and optimizing long-term follow-up care.
Nigral overexpression of alpha-synuclein in the absence of parkin enhances alpha-synuclein phosphorylation but does not modulate dopaminergic neurodegeneration
Authors: Anne-Sophie Van Rompuy, Marusela Oliveras-Salvá, Anke Van der Perren, Olga Corti, Chris Van den Haute, Veerle Baekelandt
Journal: Molecular Neurodegeneration (2015)

Alpha-synuclein is a key protein in the pathogenesis of Parkinson's disease. Mutations in the parkin gene are the most common cause of early-onset autosomal recessive Parkinson's disease, probably through a loss-of-function mechanism. However, the molecular mechanism by which loss of parkin function leads to the development of the disease and the role of alpha-synuclein in parkin-associated Parkinson's disease is still not elucidated. Conflicting results were reported about the effect of the absence of parkin on alpha-synuclein-mediated neurotoxicity using a transgenic approach. In this study, we investigated the effect of loss of parkin on alpha-synuclein neuropathology and toxicity in adult rodent brain using viral vectors. Therefore, we overexpressed human wild type alpha-synuclein in the substantia nigra of parkin knockout and wild type mice using two different doses of recombinant adeno-associated viral vectors.No difference was observed in nigral dopaminergic cell loss between the parkin knockout mice and wild type mice up to 16 weeks after viral vector injection. However, the level of alpha-synuclein phosphorylated at serine residue 129 in the substantia nigra was significantly increased in the parkin knockout mice compared to the wild type mice while the total expression level of alpha-synuclein was similar in both groups. The increased alpha-synuclein phosphorylation was confirmed in a parkin knockdown cell line.These findings support a functional relationship between parkin and alpha-synuclein phosphorylation in rodent brain.
Possible contamination of organ preservation fluid with Bacillus cereus: the United Kingdom response
Authors: C S Brown, M A Chand, P Hoffman, N Woodford, D M Livermore, S Brailsford, S Gharbia, N Small, E Billingham, M Zambon, K Grant, None on behalf of the United Kingdom incident response team
Journal: Eurosurveillance (2012)

We describe here the United Kingdom (UK) response following the recent international recall of an organ preservation fluid owing to potential Bacillus cereus contamination. This fluid is used for the transport of solid organs and pancreatic islet cells for transplant. We detail the response mechanisms, including the initial risk stratification, investigatory approaches, isolate analysis and communications to professional bodies. This report further lays out the potential need for enhanced surveillance in UK transplant patients.
Phase II trial of huN901-DM1 in patients with relapsed small cell lung cancer (SCLC) and CD56-positive small cell carcinoma
Authors: J. McCann, F. V. Fossella, M. A. Villalona-Calero, A. W. Tolcher, P. Fidias, R. Raju, S. Zildjian, R. Guild, R. Fram
Journal: Journal of Clinical Oncology (2007)

18084 Background: HuN901-DM1, a humanized antibody-maytansinoid immunoconjugagte, binds to CD56 which is expressed in almost all cases of SCLC as well as in other small cell carcinomas (SCC), neuroendocrine carcinomas, and multiple myeloma. The immunoconjugate binds to its target antigen, is internalized, then releases DM1. Methods: Patients with relapsed SCLC and CD56- positive SCC of other sites are treated with huN901-DM1 given as an intravenous infusion at 60 mg/m 2 /week for four consecutive weeks every six weeks. The study consists of two stages. Fourteen patients were initially enrolled. The occurrence of an objective response among the initial 14 patients prompted expansion to a total of 35 evaluable patients. Clinical response is evaluated by RECIST criteria. Results: To date, thirty patients have been treated in the study. Four patients experienced drug related serious adverse events (SAEs). Three patients had severe headache after the initial infusion of study drug. Symptoms markedly improved after 24 hours and then completely resolved. Severe headaches did not occur in subsequent patients who were pre-medicated with steroids prior to all infusions. A patient with a history of diabetic neuropathy and prior cisplatin treatment had grade 4 hyperesthesia. There was no evidence of clinically significant myelosuppression. HuN901-DM1 generally was well tolerated and no serious infusion reactions occurred. Preliminary pharmacokinetic (PK) data reveal no prolongation of terminal half-life of the immunoconjugate when PK parameters are compared from the first and fourth dose of cycle 1. Further, there was no evidence of antibody formation to the antibody component (HAHA) or drug component (HADA) of huN901-DM1. One patient (pt) with relapsed, SCLC had an objective partial response lasting 18 weeks and a pt with cervical SCC had an unconfirmed partial response. Stable disease was observed in five patients and lasted about 6 (3 pts), 12 (1 pt), and 18 weeks (1 pt). Conclusions: The study provides evidence of clinical activity and safety of huN901-DM1. Pre-medication with steroids appears effective in preventing severe headaches. Enrollment of additional patients to the study is planned. No significant financial relationships to disclose.
Natural history of male psychological health: IX. Empirical evidence for Erikson's model of the life cycle
Authors: George E. Vaillant, Eva Milofsky
Journal: American Journal of Psychiatry (1980)

The authors examine Erikson's model of the life cycle by reviewing two 40-year prospective studies, one of 392 men from high-crime core-city neighborhoods and the other of 94 successful college students. The empirically defined developmental stage of each man at age 47 and many other facets of each man's life course were rated by judges blind to other data. The studies identified a well-defined, career consolidation stage that falls between Erikson's stages of intimacy and generativity. The results support three hypotheses. First, the stages of men's life cycle must be passed through sequentially; failure to master one stage usually precludes mastery of subsequent stages. Second, the age at which a given stage is mastered varies enormously. Third, the stage attained by middle life appears quite independent of childhood social class or education, although adult maturation is correlated with whether childhood was conducive to basic trust, autonomy, and initiative.