tbuckley/cabot-search huggingface dataset:
Evaluation of long-term toxicity after chemotherapy for testicular cancer.
Authors: C Bokemeyer, C C Berger, M A Kuczyk, H J Schmoll
Journal: Journal of Clinical Oncology (1996)

PURPOSE The current study evaluates the extent and reversibility of late sequelae after chemotherapy in longterm survivors of testicular cancer. The influence of therapy and patient characteristics and the relationship between different toxicities are assessed. PATIENTS AND METHODS Ninety patients with a median age of 28 years (range, 19 to 53) and a median followup time of 58 months (range, 15 to 159) participated in the clinical examinations, a personal interview, and technical investigations. Overall health and the impact of late toxicity were assessed by the patients. All patients were in complete remission (CR) for at least 1 year. Chemotherapy had consisted of cisplatin (P), bleomycin (B), and vinblastine (V) in 30 patients (33%); P, B, and etoposide (E) in 26 patients (29%); P, B, E, and a vinca alkaloid in 22 patients (24%); and other P-based combination regimens in 12 patients (13%). RESULTS Alterations of gonadotropin levels (follicle-stimulating hormone [FSH] luteinizing hormone [LH]) in up to 68% of patients and Leydig cell insufficiency in one third of patients were the most frequently detected abnormalities. Approximately 20% of patients had low serum magnesium [Mg] or phosphate levels, or elevated creatinine levels. Cardiovascular risk factors were identified in one third of patients with elevated serum cholesterol levels with or without obesity; 15% had developed arterial hypertension after chemotherapy. The most frequent symptomatic toxicities were Raynaud's phenomenon (RP) in 30% of patients, ototoxicity in 21%, and peripheral neuropathy in 17%. Major risk factors for the development of toxicity were cumulative dose of P (P &lt; .0001 for ototoxicity and neurotoxicity; P &lt; .01 for overall toxicity, gonadal toxicity, and dehydroepiandrosteron elevation; P &lt; .05 for hypertension and Mg depletion) and type of chemotherapy (57% of PVB-treated patients v25% of PEB +/- vincristine-treated patients with RP; P &lt; .01). CONCLUSION The cumulative dose of P was a major predictor for toxicity. Patients and treatment characteristics such as noise exposure, age, history of smoking, and mode of B application were less important. Further clinical trials should evaluate the sequelae of chemotherapy treatment for testicular cancer prospectively.
Abstract 45: A Mathematical Model of Ventilation, Perfusion, and Oxygenation in Low-Flow States
Authors: Daniel P Davis, Paul W Davis
Journal: Circulation (2007)

Background: Recent investigations underscore the critical importance of ventilation strategies on resuscitation outcomes. In low perfusion states, such as cardiac arrest and traumatic shock, the rise in intrathoracic pressure that accompanies positive-pressure ventilation (PPV) can significantly impede venous return and lead to a decrease in cardiac output. The optimal ventilation strategy in these “low-flow” states remains unclear. Objectives: To create a mathematical model of perfusion and oxygenation to predict the effects of PPV with both normotension and hypotension. Methods: The lung pressure-volume relationship was modeled using a novel formula allowing manipulation of various lung characteristics, including vital capacity, compliance, and the upper and lower inflection points. A separate formula was then derived to predict mean intrathoracic pressure for a given minute ventilation using the pressure-volume formula. The addition of positive end-expiratory pressure was also modeled. Finally, a formula was derived to model oxygen absorbance as a function of alveolar surface area and flow based on ventilation rate and mean intrathoracic pressure. Results: Mathematical models of the lung pressure-volume relationship, mean intrathoracic pressure, and absorbance were successfully derived. Manipulation of vital capacity, compliance, upper and lower inflection points, positive end-expiratory pressure, and minute ventilation allowed prediction of optimal ventilation rate and tidal volume for a normal and an ARDS lung. For a normal lung, optimal values for both mean intrathoracic pressure and absorption were achieved with a ventilation rate of 4 breaths/min. A decrease in the upper inflection point or increase in minute ventilation resulted in faster optimal ventilation rates, although none exceeded 14 breaths/min. Conclusions: A mathematical model of ventilation was successfully created allowing manipulation of multiple variables related to lung compliance and ventilation strategy. This model suggests the use of lower ventilation rates with larger tidal volumes to minimize the hemodynamic effects of PPV and maximize oxygen absorbance.
Asthma admissions: Characteristics of patients admitted to a specialized respiratory hospital
Authors: Fabián Caro, Santiago Auteri, Daniel Colodenco, Ricardo Del Olmo, Glenda Ernst, Martín Fernández, Guillermo Menga, José Luis Morero, Eduardo Schiavi, Hugo Neffen, Santiago Rossi
Journal: European Respiratory Journal (2013)

Introduction: Admissions for asthma are life threatening events that impair patients’ quality of life. The aim of this work is to characterize the population of patients admitted to a specialized respiratory hospital. Methods: Cross sectional prospective observational study of all admissions in ≥18 years old subjects along 1 year (Jan/12-Jan13) in a specialized respiratory hospital employing a single especially devised clinical record. Results: 164 consecutive admissions were studied in 147 patients. 157(95.4%) in a general ward and 7(4.2%) in ICU, 6 (85.7%) requiring mechanical ventilation (no deaths) 97(66%) pts were female. Mean age was 43±15.2 yrs. 12(8.2%) pts were admitted twice, 4(2.7%) 3 times and 1(0.7%) 4 times. 119(81%) had night awakenings in the last month;112(76.2%) had an emergency room visit in the last year; 94(64%) had been admitted once in their life and 30(20.4%) in the last year. 25.8% fulfilled ATS criteria for difficult to control asthma and 22.4% had experienced a near fatal asthma episode (82% were women).45,5% received only SABA, 12,9% were only on ICS, 34% were on ICS+LABA. Conclusions: A high number of admissions occurred in young patients (average age 43), a clear predominance in women and with markers of uncontrolled and severe asthma in the previous month and year. In spite of these facts treatment was suboptimal in the great majority of patients. This reflects a huge gap between guideline recommendations and daily treatment of asthma even in a specialized setting.
Impact of frequent exacerbations in patients with COPD
Authors: Ahmed Ben Saad, Naceur Rouatbi, Samah Joobeur, Neji Skhiri, Saousen Cheikh Mhamed, Hadhemi Mribah, Ali El Kamel
Journal: European Respiratory Journal (2014)

Exacerbations are important events in the natural history of chronic obstructive pulmonary disease (COPD). The higher the number of COPD exacerbations, the worse are the clinical and economical consequences.  Objectives: To determine the influence of the number of exacerbations on the evolution and severity of COPD patients.  Methods: A retrospective study of COPD patients admitted to our hospital and outpatients followed for COPD over a period of 22 years. The patient is considered frequent exacerbator if the number of exacerbations is greater than or equal to 2/year.  Results: The study included 1300 COPD patients (97% male; mean age 66+/-10 years), among whom 883 (68%) were frequent exacerbators and 417 infrequent exacerbators (32%). No relationship was seen between age, gender, smoking history (pack-years) and the frequency of exacerbations. Frequent exacerbators had lower FEV1 (1.1 L versus 1.52 L for infrequent exacerbators, p
Role of C-terminal pro-endothelin in pulmonary hypertension
Authors: Ralf Kaiser, Philipp M. Lepper, Robert Bals, Heinrike Wilkens
Journal: European Respiratory Journal (2012)

Introduction: The endothelin pathway is upregulated in various forms of pulmonary hypertension. Its disease promoting activity has lead to the development of endothelin receptor blockers as specific therapeutics. The highly unstable active form requires greatest care in sample preparation to acquire reproducable results. In this study we examined the role of the more stable CT-proET in pulmonary hypertension using a high precision and standardized system.

Methods: We examined 36 patients retrospectively. Therapy was applied following contemporary guidelines. Samples of platelet free EDTA plasma were stored at -80°C since collection between 2000 and 2003. Biomarker levels were determined by a Kryptor compact (BRAHMS, Germany) according to vendor instructions.

Results: Patients were categorized according to DanaPoint classification as class 1 (n=16), class 2 (n=1), class 3 (n=9), class 4 (n=8) and class 5 (n=2). The mean follow-up time was 4.67 years. Survivors had significantly lower levels of CT-proET (53.7 [31.2-171.8] vs 91.1 [30.6-151.6] pmol/L, p=0.006). ROC analysis for survival yielded an AUC of 80.8%. The optimized cut-off for survival was determined as 65pmol/L. The log-rank test of Kaplan-Meier-analysis for survival was highly significant (p=0.01) with a hazard ratio of 3.06.

Conclusions: CT-proET was significantly elevated in non-survivors of the follow-up period. Optimized cut-offs at 65pmol/L resulted in a significant Kaplan-Meier-analysis for survival. CT-proET-levels above 65 pmol/L are associated with decreased survival in pulmonary hypertension. CT-proET might be a useful biomarker to determine high-risk patients, while offering the advantage of a stable product of the endothelin cascade.
Usefulness of real-time PCR for lytA, ply, and Spn9802 on plasma samples for the diagnosis of pneumococcal pneumonia
Authors: G. Abdeldaim, B. Herrmann, P. Mölling, H. Holmberg, J. Blomberg, P. Olcén, K. Strålin
Journal: Clinical Microbiology and Infection (2009)
Clinical Activity and Safety of Medi4736, an Anti-Pd-L1 Antibody, in Patients with Head and Neck Cancer
Authors: M. Fury, S.I. Ou, A. Balmanoukian, A. Hansen, E. Massarelli, A. Blake-Haskins, X. Li, P.B. Robbins, J. Vasselli, N.H. Segal
Journal: Annals of Oncology (2014)
Clinical and inflammatory characteristics of 'unreported' COPD exacerbations
Authors: Maria Calderazzo, Maria-Belen Trujillo-Torralbo, Sarah Elkin, Sebastian Johnston, Patrick Mallia
Journal: European Respiratory Journal (2013)

Background. COPD patients frequently experience deteiorations in symptoms that are not reported to healthcare providers ('unreported exacerbations'), however it is debated whether these episodes constitute true exacerbations. Some studies only define exacerbations as events that result in contact with a healthcare provider and treatment with oral corticosteroids/antibiotics and therefore exclude unreported exacerbations. No studies have evaluated whether unreported exacerbations have similar physiological and inflammatory profiles to reported exacerbations.

Methods. We recruited a cohort of COPD patients and performed an evaluation at baseline and when they reported exacerbations. We did not institute treatment. Patients made their own decisions regarding contacting their usual medical practitioners and/or commencing treatment.

Results. 13 exacerbations were evaluated that patients did not report to healthcare providers and were not treated. The clinical and inflammatory parameters are shown in Table 1. Unreported exacerbations were associated with significant falls in PEF and significant increases in CRP and sputum inflammatory cell counts.

View this table:



Conclusions. Exacerbations that patients do not report to healthcare providers are associated with significant airflow obstruction and airways and systemic inflammation. Therefore even unreported exacerbations are likely to be genuine events that contribute to the progression of COPD. Further research is needed into the factors that influence patients' decisions not to report exacerbations.
Induced Cardiovascular Procedural Costs and Resource Consumption Patterns After Coronary Artery Calcium Screening
Authors: Leslee J. Shaw, James K. Min, Matthew Budoff, Heidi Gransar, Alan Rozanski, Sean W. Hayes, John D. Friedman, Romalisa Miranda, Nathan D. Wong, Daniel S. Berman
Journal: Journal of the American College of Cardiology (2009)
Impact of chronic air pollution exposure on non-cystic fibrosis bronchiectasis: Hit the road?
Authors: Pieter Goeminne, Esmée Bijnens, Ben Nemery, Tim Nawrot, Lieven Dupont
Journal: European Respiratory Journal (2013)

Introduction: Both acute and chronic air pollution exposure have been shown to influence cystic fibrosis bronchiectatic disease. (1,2) Air pollution in non-cystic fibrosis bronchiectasis (NCFB) has not been studied before. We studied the association between residential distance to major road and death in a cohort of patients with NCFB.  Methods: We included 189 patients between 18 and 65 years who had visited the outpatient clinic at the University Hospital of Leuven, Belgium, between June 2006 and October 2012. All patients had chronic productive cough and a chest CT scan confirming NCFB. We calculated the hazard ratios (HR) for mortality in relation to proximity of the home to major roads, adjusting for relevant covariables.  Results: Of the 189 patients (45% male, 49 years ± 13), 20 died during the study period. Patients with a history of Pseudomonas aeruginosa in their sputum had a 3.6 fold increased risk of dying during follow-up (p=0.01). Never smokers showed a reduced risk (HR=0.30; p=0.03) and chronic macrolide therapy appeared protective (HR=0.34; p=0.07). Independently from gender, age, Pseudomonas aeruginosa in sputum and macrolide therapy, residential proximity to a major road was associated with the risk of mortality (HR=0.40; p=0.01; for a tenfold increase in distance to a major road).  Conclusion: Living close to a major road is associated with a higher risk of dying in patients with NCFB. A history of Pseudomonas aeruginosa in sputum has a negative effect on mortality while patients who never smoked and patients receiving chronic macrolide therapy have a lower mortality risk.  1. Goss et al., Am J Respir Crit Care Med 2004  2. Goeminne et al., Chest 2012, in press.
Semi-quantitative X-ray microanalysis of bronchoalveolar lavage samples from silica-exposed and nonexposed subjects
Authors: M Lusuardi, A Capelli, CF Donner, O Capelli, G Velluti
Journal: European Respiratory Journal (1992)

To evaluate the possibility of quantifying alveolar dust burden in conditions of exposure to silica, four groups of subjects were submitted to bronchoalveolar lavage (BAL): 10 healthy control subjects and 39 patients affected by diffuse interstitial lung disease (DILD) never exposed to dust, 23 silicotic patients and 12 chronic bronchitis patients with a history of occupational exposure to silica dust. Five to ten million BAL recovered cells were analysed with an energy-dispersive X-ray microanalysis (EDXA) system to determine the silicon content, expressed in a semi-quantitative way as silicon to sulphur (Si/S) ratio. The results were independent of smoking habit. The Si/S median values (interquartile range in brackets) for the four groups were 0.53 (0.5-0.65), 0.60 (0.41-0.8), 1.23 (1.06-1.39), 1.31 (1.11-1.97), respectively. Silicotics and simply exposed individuals did not show a significant discrepancy, but they were both significantly different in comparison with normal and DILD patients without history of exposure (p less than 0.001). 14.3% false negative cases were found, and 4.1% false positive cases (none among normal subjects). We did not see any significant relationships between the amount of silicon and the duration of exposure or the degree of chest X-ray involvement. A study of cytocentrifuge slides from the same subjects by polarizing light microscopy revealed a lower sensitivity (34% false negative cases).(ABSTRACT TRUNCATED AT 250 WORDS)
Allopurinol: Intravenous Use for Prevention and Treatment of Hyperuricemia
Authors: Richard V. Smalley, Al Guaspari, Sandra Haase-Statz, Susan A. Anderson, Donna Cederberg, John A. Hohneker
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To tabulate data obtained over a 21-year period to determine the efficacy and safety of an intravenous (IV) allopurinol preparation. PATIENTS AND METHODS: IV allopurinol was provided on a compassionate plea basis to patients of any age in whom xanthine oxidase inhibitor therapy was indicated as an adjunct to chemotherapy and for whom oral intake was restricted. Three hundred twenty-seven investigators at multiple hospitals in the United States treated 1,172 patients with IV allopurinol. The vast majority of these patients had a malignancy and were in danger of developing tumor lysis syndrome (TLS) and subsequent acute uric acid nephropathy (AUAN) and were unable to take oral allopurinol. Data referable to the time period of IV allopurinol administration were collected, collated, and analyzed retrospectively. There was no randomization. RESULTS: In patients initiating treatment for an elevated serum uric acid (SUA), the SUA normalized or improved in 87% of adult patients and normalized or improved in 95% of pediatric patients. IV allopurinol, administered prophylactically to patients at high risk of developing hyperuricemia and TLS, prevented an increase in SUA levels in 93% of adults and 92% of children. Toxicities caused by IV allopurinol were minimal and consisted of 10 instances of mild to moderate skin or allergic reactions. CONCLUSION: IV allopurinol is as efficacious and safe as oral allopurinol and will be of significant benefit to patients at risk of TLS and AUAN and unable to take oral medication.
Abstract 9974: Inadequate Lipid Target Achievement Among US Treated Adults with Dyslipidemia
Authors: Nathan D Wong, Kalina Wong, Amy Phan, Elizabeth Marrett, Dena R Ramey, David R Neff
Journal: Circulation (2011)

Background: Despite available medications for dyslipidemia, many treated persons still have suboptimal lipid levels. We examined the extent of residual dyslipidemia in U.S. adults. Methods: We studied a sample of 2679 U.S. adults aged 18 and over from the National Health and Nutrition Examination Survey 2007-2008, of which 1473 (55%) were defined to have dyslipidemia, based on modified 2004 National Cholesterol Education Program - Adult Treatment Panel III Update and 2006 American Heart Association/American College of Cardiology cutpoints for LDL-C along with the Framingham risk score for cardiovascular disease or if on pharmacologic treatment. Of these, 669 (45.4%) were on pharmacologic treatment. Among this group, we examined the proportions of individuals who still had LDL-C not at goal, low HDL-C, and/or elevated triglycerides.Results were projected to represent the U.S. adult population in millions. Results: In this cohort treated for dyslipidemia, mean (SD) age was 61.2 (12.1) years, and 49.8% were male. Over half (55.0%) were of non-Hispanic white, 24.8% Hispanic and 16.1% African American race. Only 17.6% of subjects on treatment for dyslipidemia were at recommended levels for all three lipids (LDL-C, HDL-C, and triglycerides). LDL-C remained above goal for 63% of subjects, 28% had low HDL-C, and 42% had elevated triglycerides. Two lipid abnormalities were identified in 27.5% of subjects and 12% had all three lipid parameters not at recommended levels (figure). Conclusion: Despite widely available treatments for dyslipidemia, many persons remain not at LDL-C goal and/or at recommended levels for other lipids, indicating opportunities for more intensive combination lipid-lowering treatment and efforts to improve adherence.
Which are the most informative parameters to follow the respiratory decline in Duchenne muscular dystrophy
Authors: Sonia Khirani, Adriana Ramirez, Guillaume Aubertin, Michèle Boulé, Chrystelle Chemouny, Veronique Forin, Brigitte Fauroux
Journal: European Respiratory Journal (2012)

Rationale 

Duchenne muscular dystrophy causes progressive respiratory muscle weakness. Few information is available on the natural evolution of respiratory parameters in boys with Duchenne muscular dystrophy.

Objectives 

In order to identify respiratory parameters associated with the earliest decline, lung function, blood gases, respiratory mechanics, and respiratory muscle strength were measured in 48 boys with Duchenne muscular dystrophy (mean age 12.7 ± 3.4, range 7.6 – 19.0 years), over a period of 10 years.

Main Results 

Only four parameters showed an important decline with age. Gastric pressure during cough was below normal in all patients with a mean 5.7 ± 3.8 cmH2O decline per year. Sniff nasal inspiratory pressure tended to increase before the age of 10 years followed by a rapid decline (mean decrease 4.8 ± 4.9 cmH2O or 5.2 ± 4.4 % predicted per year). Absolute forced vital capacity values peaked around 13-14 years of age and remained mainly over 1 liter but predicted values showed a mean 4.1 ± 4.4 % decline per year. Diaphragmatic tension time index increased above normal after the age of 14 years old with a mean increase of 0.04 ± 0.04 point per year.

Conclusion 

Repeated gastric pressure during cough, sniff nasal inspiratory pressure, and forced vital capacity measurements provide simple tools to assess the progression of respiratory muscle weakness in young boys with Duchenne muscular dystrophy. Endurance indexes decline at a later age. These indexes may help to monitor treatment effects.
Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice
Authors: J Etchin, J Montero, A Berezovskaya, B T Le, A Kentsis, A L Christie, A S Conway, W C Chen, C Reed, M R Mansour, C E L Ng, S Adamia, S J Rodig, I A Galinsky, R M Stone, B Klebanov, Y Landesman, M Kauffman, S Shacham, A L Kung, J C Y Wang, A Letai, A T Look
Journal: Leukemia (2015)
Inhibition Of Myeloid Derived Suppressor Cells (MDSC) In The Multiple Myeloma Bone Marrow Microenvironment
Authors: Gullu Topal Gorgun, Hiroto Ohguchi, Teru Hideshima, Yu-Tzu Tai, Noopur Raje, Nikhil C. Munshi, Paul G. Richardson, Jacob P. Laubach, Kenneth C. Anderson
Journal: Blood (2013)
G proteins: implications for psychiatry
Authors: H K Manji
Journal: American Journal of Psychiatry (1992)

There is mounting evidence that a family of guanosine triphosphate binding proteins (G proteins) play an obligatory role in the transduction of a vast array of extracellular, receptor-detected signals across cell membranes to intracellular effectors. The author reviews the literature dealing with G protein coupling to second messenger generation, the role of G proteins in regulating both the convergence and divergence of neurotransmitter action in the CNS, and the involvement of G proteins in a variety of clinical conditions, with an emphasis on psychiatric conditions and their treatments. G proteins from the basis of signal integration in the CNS, endowing the neuron with a large degree of functional diversity. Abnormalities in the function and/or expression of G proteins have been implicated in a variety of pathophysiologic states, and a number of currently available psychotropic drugs affect G proteins. The understanding of the mechanisms by which G proteins modulate neuronal activity may be one of the keys to understanding the functioning and the complexities of the nervous system. Given their widespread, critical roles in the regulation of neuronal function, it seems likely that G proteins are involved in the pathophysiology of various major psychiatric illnesses. The development of novel, site-specific drugs with primary G protein targets remains an exciting prospect for the future.