tbuckley/cabot-search huggingface dataset:
Sputum Induction in Severe Asthma by a Standardized Protocol
Authors: ANNEKE ten BRINKE, CINDY de LANGE, AEILKO H. ZWINDERMAN, KLAUS F. RABE, PETER J. STERK, ELISABETH H. BEL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Sputum induction is a noninvasive method to evaluate airway inflammation. We investigated whether it can be safely and successfully performed in patients with severe, difficult-to-control asthma, and whether the patients at risk can be identified. Ninety-three severe asthmatics were included, all symptomatic despite inhaled corticosteroids ( ⩾ 1,600 μ g/d) and long-acting β2-agonists > 1 yr. Patients with a postbronchodilator FEV1 < 1 L and < 50% predicted were excluded from participation. Sputum induction was performed according to a strict protocol, using 0.9%, 3.0%, and 4.5% NaCl inhalation. In 74% (CI: 64 to 83%) of patients an adequate sputum sample could be obtained. Twenty-two percent (CI: 14 to 33%) developed excessive bronchoconstriction (decrease in FEV1 > 15% from baseline) despite the continuing use of long-acting bronchodilators and pretreatment with 400 μ g salbutamol. The decrease in FEV1 was associated with increased use of rescue short-acting β2-agonists in the previous 2 d (rs = 0.51, p = 0.002), lower postbronchodilator FEV1 (rs = − 0.31, p = 0.004), and lower provocative concentration of histamine causing a 20% reduction in FEV1 (PC20) (rs = − 0.52, p < 0.001). Recent use of short-acting β2-agonist increased the risk for excessive bronchoconstriction 10.2-fold (CI: 1.2 to 109.8). In conclusion, sputum induction can be safely and successfully performed in patients with severe, difficult-to-control asthma if a standardized protocol is used. However, severe bronchoconstriction may occur despite regular use of long-acting β2-agonist and pretreatment with salbutamol 400 μ g. In particular, patients who have used additional short-acting β2-agonists as rescue medication during the days preceding the induction, are at high risk.Keywords: asthma; bronchoconstriction; safety; saline solution, hypertonic; sputum
Models of Care and NCCN Guideline Adherence in Very-Low-Risk Prostate Cancer
Authors: Ayal A. Aizer, Jonathan J. Paly, Anthony L. Zietman, Paul L. Nguyen, Clair J. Beard, Sandhya K. Rao, Irving D. Kaplan, Andrzej Niemierko, Michelle S. Hirsch, Chin-Lee Wu, Aria F. Olumi, M. Dror Michaelson, Anthony V. D’Amico, Jason A. Efstathiou
Journal: Journal of the National Comprehensive Cancer Network (2013)

NCCN Guidelines recommend active surveillance as the primary management option for patients with very-low-risk prostate cancer and an expected survival of less than 20 years, reflecting the favorable prognosis of these men and the lack of perceived benefit of immediate, definitive treatment. The authors hypothesized that care at a multidisciplinary clinic, where multiple physicians have an opportunity to simultaneously review and discuss each case, is associated with increased rates of active surveillance in men with very-low-risk prostate cancer, including those with limited life expectancy. Of 630 patients with low-risk prostate cancer managed at 1 of 3 tertiary care centers in Boston, Massachusetts in 2009, 274 (43.5%) had very-low-risk classification. Patients were either seen by 1 or more individual practitioners in sequential settings or at a multidisciplinary clinic, in which concurrent consultation with 2 or more of the following specialties was obtained: urology, radiation oncology, and medical oncology. Patients seen at a multidisciplinary prostate cancer clinic were more likely to select active surveillance than those seen by individual practitioners (64% vs 30%; P<.001), an association that remained significant on multivariable logistic regression (odds ratio [OR], 4.16; P<.001). When the analysis was limited to patients with an expected survival of less than 20 years, this association remained highly significant (72% vs 34%, P<.001; OR, 5.19; P<.001, respectively). Multidisciplinary care is strongly associated with selection of active surveillance, adherence to NCCN Guidelines and minimization of overtreatment in patients with very-low-risk prostate cancer.
Analysis of human transcriptomes
Authors: Victor E Velculescu, Stephen L Madden, Lin Zhang, Alex E Lash, Jian Yu, Carlo Rago, Anita Lal, Clarence J Wang, Gary A Beaudry, Kristin M Ciriello, Brian P Cook, Michael R Dufault, Anne T Ferguson, Yuhong Gao, Tong-Chuan He, Heiko Hermeking, Siewleng K Hiraldo, Paul M Hwang, Marissa A Lopez, Hilary F Luderer, Brynna Mathews, Joseph M Petroziello, Kornelia Polyak, Leigh Zawel, Wen Zhang, Xiaoming Zhang, Wei Zhou, Frank G Haluska, Jin Jen, Saraswati Sukumar, Gregory M Landes, Gregory J Riggins, Bert Vogelstein, Kenneth W Kinzler
Journal: Nature Genetics (1999)
Anti-IgE treatment: An alternative for severe allergic occupational asthma
Authors: François Lavaud, Gérard Pfeiffer, Philippe Bonniaud, Jean-Charles Dalphin, Christophe Leroyer, Dominique Muller, Gilles Mangiapan, Frédéric de Blay
Journal: European Respiratory Journal (2012)

Severe work-related asthma remains a difficult problem and new alternative treatment must be evaluated to obtain asthma control and ideally the sustain of the occupational activity.  During 2 years we have enrolled 10 occupational asthmatics (8 men, 2 women, mean age 37, suffering of asthma from 0,5 to 8 years. They were all severe uncontrolled asthma (GINA recommendations). The mean dose of inhaled corticosteroids was 3200 µg/day of beclometasone equivalent. All patients had 2 to 8 severe exacerbations/year. Six patients were allergic to a high molecular weight agent (wheat flour: 2, cat: 1, rabbit: 1, storage mites: 1,  Alternaria : 1). In 4 patients the causative agent was a low molecular weight compound (isocyanates in 2 cases, acrylates one case, perchlorethylene one case). Total IgE levels were always above 30 U/mL. The follow-up was performed from 6 to 48 months. Asthma parameters and the occupational status were registered every 6 months.  Results showed a reduction of severe exacerbations in 9 patients. Only one patient was “ non responder” after 6 months of treatment. In the 9 “responders” an optimal control could be obtained in 4 patients. Oral daily corticosteroids could be decreased in the 5 (mean initial dose 8,6 mg/day to 1,2 mg/day of equivalent prednisone). Days off-work because of asthma were reduced in the 9 “responders”. 7 could continue to work with amendment of the working place. We suggest that omalizumab could be a potential treatment for severe uncontrolled work-related asthma in 3 conditions, patients who were unable to avoid allergen exposure, persistent asthma after cessation of the offending exposure and work-aggravated asthma symptoms in workers with pre-existing allergic asthma.
Entrainment of Respiration in Humans by Periodic Lung Inflations
Authors: PEGGY M. SIMON, ADEL S. ZUROB, WILLIBALD M. WIES, J. C. LEITER, ROLF D. HUBMAYR, MERILYN L. JENSEN, RANDOLPH W. STROETZ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhythm of the patient fails to entrain to machine inflations. Entrainment implies a resetting of the respiratory rhythm such that a fixed temporal relationship exists between the onset of inspiratory activity and the onset of a mechanical breath. We examined the entrainment response to mechanical ventilation of normal humans over a range of machine rates during wakefulness and during isocapnic and hypercapnic NREM sleep. Wakefulness facilitated 1:1 entrainment of the respiratory rhythm to the mechanical ventilator over a wider range of machine frequencies than during NREM sleep (p < 0.001); isocapnic and hypercapnic conditions did not differ (p = 0.95). To evaluate the Hering–Breuer reflexes in the resetting of the respiratory rhythm during sleep, we examined changes in neural inspiratory time (Ti) as the relationship between inspiratory efforts and onset of machine inflations changed. As inspiratory efforts extended into the machine inflation cycle, neural Ti shortened. We conclude that entrainment responses of normal humans to mechanical ventilation differ depending on state, but mild increases in respiratory drive caused by CO2 stimulation do not affect these entrainment responses. Furthermore, the changes in neural Ti are consistent with observations in animal studies in which Hering–Breuer reflexes mediated entrainment.
Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes
Authors: Laureline Berthelot, Thomas Robert, Vincent Vuiblet, Thierry Tabary, Antoine Braconnier, Moustapha Dramé, Olivier Toupance, Philippe Rieu, Renato C. Monteiro, Fatouma Touré
Journal: Kidney International (2015)

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, frequently leads to end-stage renal disease and kidney transplantation. However, disease recurrence often occurs after transplantation. Here we evaluated the predictive value of three markers for IgAN recurrence: the presence of galactose-deficient IgA1, IgG anti-IgA autoantibodies, and IgA-soluble (s) CD89 complexes. This was analyzed in 38 kidney transplant recipients with IgAN recurrence and compared with 22 patients transplanted for IgAN but without recurrence and with 17 healthy controls. Pre-transplantation galactose-deficient IgA1 serum levels were significantly higher in the recurrence compared with the no recurrence or control groups. IgA-IgG complexes were significantly elevated in the recurrence group. Both the recurrence and no recurrence groups had increased values of IgA-sCD89 complexes compared with healthy controls, but values were significantly lower in patients with recurrence compared with no recurrence. Areas under the receiver operating curve of the markers in pre-transplantation sera were 0.86 for galactose-deficient-IgA, 0.82 for IgA-IgG, and 0.78 for sCD89-IgA; all significant. Disease recurrence was associated with decreased serum galactose-deficient IgA1 and appearance of mesangial-galactose-deficient IgA1 deposits, whereas increased serum IgA-sCD89 complexes were associated with mesangial sCD89 deposits. Thus, galactose-deficient-IgA1, IgG autoantibodies, and IgA-sCD89 complexes are valuable biomarkers to predict disease recurrence, highlighting major pathogenic mechanisms in IgAN.
Abstract A14: Hyperactivation of RSK1 is a hallmark of metastatic nodular melanoma
Authors: Amel Salhi, Joshua A. Farhadian, Keith M. Giles, Eleazar C. Vega-Saenz de Miera, Ines Pires Da Silva, Caitlin Bourque, Karen Yeh, Sagar Chhangawala, Jinhua Wang, Fei Ye, David Y. Zhang, Eva Hernando-Monge, Yariv Houvras, Iman Osman
Journal: Cancer Research (2015)

Abstract It is generally accepted that superficial spreading (SSM) and nodular melanoma (NM), the most common melanoma histologic subtypes, are biologically indistinct once they invade and metastasize. Consequently, targeted therapy is dictated by the mutational profile of metastatic disease, regardless of the histologic subtype of the primary melanoma. Here, we show that p90 ribosomal S6 kinase (RSK1) is constitutively phosphorylated in human melanoma cell lines derived from NM but not SSM. Significantly, metastases from primary NM patients showed p-RSK1 overexpression and a distinct metalloproteinase profile compared with metastases from primary SSM patients. Interestingly, p-RSK1 hyper-activation could not be solely explained by MAPK activation due to BRAF mutations. We show that NM-derived cell lines were more sensitive to genetic and pharmacological RSK1 inhibition than SSM-derived cell lines. Using a zebrafish model, we demonstrate that activated RSK1 significantly accelerates melanoma progression. In addition, RNAseq revealed up-regulation of extracellular matrix degradation, cell migration, and cell proliferation genes in the RSK1 mutant-expressing tumors. Together, our data demonstrate that metastatic melanoma originating from different histologic subtypes might depend on distinct oncogenic pathways. Data also support constitutive RSK1 activation as a driver of nodular metastatic melanoma, a finding that supports the concept of subtype-specific melanoma therapy. Citation Format: Amel Salhi, Joshua A. Farhadian, Keith M. Giles, Eleazar C. Vega-Saenz de Miera, Ines Pires Da Silva, Caitlin Bourque, Karen Yeh, Sagar Chhangawala, Jinhua Wang, Fei Ye, David Y. Zhang, Eva Hernando-Monge, Yariv Houvras, Iman Osman. Hyperactivation of RSK1 is a hallmark of metastatic nodular melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A14.
Exacerbations of Asthma
Authors: Z. Diamant
Journal: European Respiratory Journal (2007)

Edited by S.L. Johnston and P.M. OByrne 

Published by Informa Healthcare 

Pages: 354. Price: £95.00. ISBN: 1-84214-318-2 

Exacerbations of Asthma    This book deals specifically with a clinically important feature of asthma, i.e. exacerbations. It is subdivided into six main sections, each dealing with several aspects of asthma exacerbations. The sections deal with relevant topics, including: epidemiology; pathophysiology; in vitro and in vivo experimental models; treatment; prevention; and delivery of care. Each section has several chapters. This set-up provides a nice overview of the current knowledge on asthma exacerbations in both children and adults reviewed from different angles.

The topics are discussed in an informative and adequate manner and instructive tables and …
Our first steps in osteosynthesis of fractured ribs using Matrix Rib technologies
Authors: Sergey Pushkin, Armen Benyan
Journal: European Respiratory Journal (2012)

Objective. Surgical management of multiple fractured ribs is the one of the undecided questions of thoracic trauma.  Aim – illustration of our experience of osteosynthesis of fractured ribs using Matrix Rib technologies.  Materials and methods. Since December 2011 we have operated 5 patients. All they had blunt thoracic trauma with multiple fractured ribs and other injuries. Number of fractured ribs was from 4 to 9. Three patients had bilateral rib fractures. Also, 2 patients had hemothorax, 1 patient had fracture of sternum, and 1 patient had rupture of left cupula of diaphragm. The middle terms from moment of trauma to operation were 1,5 days. To all of patients we have applied Matrix Rib technologies for rib osteosynthesis. The number of synthesized ribs was from 2 to 5.  Also we have performed 3 thoracoscopy (1 including suturing of diaphragm) and 1 osteosynthesis of sternum.  Results. We have observed all 5 patients during postoperative period. The average of ventilation days was 2,4. There were no respiratory or wound complications. All patients had early activation. The respiratory function improved rapidly, increase of FVC before discharge was 25%. Long-term results didn9t show any significant respiratory failure.  Conclusion. The osteosynthesis is the indicated operation at multiple and bilateral rib fractures. It helps to early activation, prevents complications and improves respiratory function.
Direct Ophthalmoscopy versus Slit Lamp Biomicroscopy in Diagnosis of the Acute Red Eye
Authors: D F Anderson, P M Sullivan, A J Luff, A R Elkington
Journal: Journal of the Royal Society of Medicine (1998)

The causes of red eye range from trivial to life-threatening, and many general practitioners are uncertain of their ability to diagnose them with the aid of an ophthalmoscope. We tested the hypothesis that, in the assessment of a patient with red eye, a doctor using a slit lamp biomicroscope would not differ in diagnostic accuracy from a doctor using a direct ophthalmoscope. A cross-over study was conducted in 98 patients newly attending an eye casualty department. 71% of diagnoses agreed exactly, and all potentially sight-threatening lesions were either diagnosed correctly or managed appropriately by doctors using an ophthalmoscope. We conclude that the initial diagnosis and management of patients with an acute red eye is not prejudiced by the lack of a slit lamp biomicroscope.
Dysfunctional breathing in asthma: is it common, identifiable and correctable?
Authors: M D L Morgan
Journal: Thorax (2002)

Objectives: To estimate the prevalence of dysfunctional breathing in adults with asthma treated in the community. Design: Postal questionnaire survey using Nijmegen questionnaire. Setting: One general practice with 7033 patients. Participants: All adult patients aged 17–65 with diagnosed asthma who were receiving treatment. Main outcome measure: Score >23 on Nijmegen questionnaire. Results: 227/307 patients returned completed questionnaires; 219 (71.3%) questionnaires were suitable for analysis. 63 participants scored >23. Those scoring >23 were more likely to be female than male (46/ 132 (35%) v 17/87 (20%), p=0.016) and were younger (mean (SD) age 44.8 (14.7) v 49.0 (13.8), p=0.05). Patients at different treatment steps of the British Thoracic Society asthma guidelines were affected equally. Conclusions: About a third of women and a fifth of men had scores suggestive of dysfunctional breathing. Although further studies are needed to confirm the validity of this screening tool and these findings, these prevalences suggest scope for therapeutic intervention and may explain the anecdotal success of the Buteyko method of treating asthma. (BMJ 2001;322:1098–100)
Survival following early hormone therapy for men with rapid PSA doubling time within 2 years following radical prostatectomy
Authors: B. Trock, M. Han, E. B. Humphreys, A. W. Partin, M. A. Eisenberger, P. C. Walsh
Journal: Journal of Clinical Oncology (2009)

5065 Background: Early hormonal therapy has been used in the salvage setting for men with biochemical recurrence following radical prostatectomy (RP), but no studies to date have been able to evaluate whether such treatment prolongs survival. We examined the impact of salvage hormonal therapy on overall survival (OS) in a cohort with long-term follow-up, and attempted to identify the subgroup most likely to benefit. Methods: Retrospective analysis of a cohort of 488 men undergoing RP at Johns Hopkins Hospital from 1982–2004, who experienced biochemical recurrence and received no salvage therapy (n = 386) or salvage hormonal therapy (n = 102); no one received adjuvant therapy. Survival was defined from biochemical recurrence to death from all causes, and analyzed with proportional hazards models with time-dependent covariates. Results: With median follow-up of 6 years after recurrence and 9 years after RP, there were 143 deaths (29%), including 105 from prostate cancer. After adjusting for PSA doubling time (PSADT), RP Gleason score, and year of surgery, hormonal therapy did not significantly improve OS for all men, compared to no salvage therapy: hazard ratio (HR) = 0.72 (95% confidence interval (CI): 0.45–1.17), p = 0.187. However, when restricted to men with early recurrence, i.e. within 2 years of RP, and with a rapid PSADT&lt;6 months, hormonal therapy was associated with a large, significant improvement in OS: HR = 0.25 (95% CI: 0.08–0.71), p = 0.0095. This subgroup comprised 22% of the cohort. In contrast, there was no benefit of salvage hormonal therapy in men with early recurrence and PSADT&gt;6 months: HR = 1.96 (95% CI: 0.89–4.31), p = 0.093, nor those who recurred more than 2 years after RP, regardless of PSADT. Conclusions: This study suggests that early salvage hormonal therapy may significantly and substantially prolong overall survival in the subgroup of men who experience an early biochemical recurrence with a rapid PSADT. These results are consistent with early recurrences being indicative of metastatic disease, while later recurrences are more likely to represent local recurrence. If validated, these results may provide useful stratification criteria for clinical trials. No significant financial relationships to disclose.
Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease.
Authors: J Yahalom, S C Gulati, M Toia, P Maslak, E G McCarron, J P O'Brien, C S Portlock, D J Straus, J Phillips, Z Fuks
Journal: Journal of Clinical Oncology (1993)

PURPOSE To evaluate the feasibility and therapeutic effect of accelerated hyperfractionated total-lymphoid irradiation (TLI), high-dose chemotherapy, and autologous bone marrow transplantation (AuBMT) in patients with relapsing or chemotherapy-resistant Hodgkin's disease (HD). PATIENTS AND METHODS Forty-seven patients with HD who either relapsed after chemotherapy (n = 19), or failed to respond (n = 28) to at least two regimens of combination chemotherapy were studied. No patient received prior radiation therapy (RT). Treatment started with reinduction with standard-dose chemotherapy, followed by involved-field irradiation (15 Gy) to areas of relapsed or persistent disease and TLI (20.04 Gy given in 1.67 Gy fractions three times per day for 4 days). Subsequently, patients received etoposide and high-dose cyclophosphamide, followed by infusion of unpurged autologous bone marrow. All surviving patients had a minimum follow-up duration of 1 year. The median follow-up duration for survivors was 40+ months, and the maximum follow-up duration was 80+ months. RESULTS Of the 47 patients treated, eight (17%) died of toxicity during the peritransplant period. Twenty-nine of the remaining 39 assessable patients (74%) attained a complete response (CR), while 10 remained with residual disease and progressed early after AuBMT. Four of the CR patients (14%) relapsed and 25 patients remained alive and free of disease. The actuarial disease-free survival (DFS) rate for the entire group at 6.5 years was 50%. Patients who received the protocol for relapsing HD had a significantly better DFS rate (79%) compared with patients treated for continuous refractory disease (DFS, 33%; P &lt; .03). CONCLUSION Previously unirradiated patients with relapsing or chemotherapy-resistant HD who have exhausted conventional chemotherapy may still respond to an aggressive therapeutic approach consisting of accelerated hyperfractionated TLI, high-dose chemotherapy, and AuBMT rescue. This program offers a potential for long-term DFS to approximately one half of patients who would otherwise have a dismal prognosis with standard-dose salvage therapy.