tbuckley/cabot-search huggingface dataset:
Lineage effects and the index of dispersion of molecular evolution.
Authors: J H Gillespie
Journal: Molecular Biology and Evolution (1989)

Recent efforts to estimate the index of dispersion [R(t)] of molecular evolution-i.e., the ratio of the variance in the number of substitutions on a lineage to the mean number-have suffered from an inability to adjust the data for lineage effects. These effects may include the generation-time dependency of the rate of evolution or improper assumptions about the branching pattern of a phylogenetic tree. In the present paper a method for correcting for lineage effects in the estimation of R(t) is presented for trees made up of three species. The recent data published by Li et al. for 20 loci in three orders of mammals is examined, and the average R(t), corrected for lineage effects, is shown to be 7.75 for replacement substitutions and 3.3 for silent substitutions. Thus the high values reported earlier may not be dismissed as due to generation-time effects or improper assumptions about phylogenies. Computer simulations are presented to give confidence in the estimate for replacement substitutions but also to demonstrate that the estimate for silent substitutions is sensitive to corrections for multiple substitutions and is not as reliable. This work's implications for our understanding of the mechanism of molecular evolution are discussed, and the arguments in favor of the hypothesis that replacement substitutions are mostly selected while silent substitutions are mostly neutral is presented.
The evaluation of living renal transplant donors
Authors: B L Kasiske, M Ravenscraft, E L Ramos, R S Gaston, M J Bia, G M Danovitch
Journal: Journal of the American Society of Nephrology (1996)

Kasiske, B L; Ravenscraft, M; Ramos, E L; Gaston, R S; Bia, M J; Danovitch, G M Author Information
Comparison of Child-Pugh (CP) criteria and NCI organ dysfunction working group (NCI-ODWG) criteria for hepatic dysfunction (HD): Implications for chemotherapy dosing
Authors: H. Patel, M. J. Egorin, S. C. Remick, D. Mulkerin, C. H. M. Takimoto, J. H. Doroshow, D. Potter, S. P. Ivy, A. J. Murgo, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2004)

6051 Background: Patients with HD may require drug dose modification based on the severity of HD. HD is often assessed using CP criteria, the use of which is advocated by the FDA. CP criteria, originally developed for patients with end-stage liver disease, has 5 components -total bilirubin (TB), albumin, prothrombin time, ascites & encephalopathy. NCI-ODWG sponsored trials have used different criteria which utilize two objective and readily measurable laboratory parameters specifically - TB & aspartate aminotransferase (AST). Comparison of these 2 criteria has not been done previously. Methods: Forty-five patients with varying degrees of HD were enrolled in a Phase I clinical trial of imatinib mesylate. Data to assess CP score were collected prospectively, along with AST. Patients were stratified into 4 groups as per the NCI-ODWG criteria based on TB & AST: normal [TB & AST ≤ upper limit of normal (ULN)], mild HD (TB > ULN to 1.5 x ULN or AST > ULN), moderate HD (TB >1.5–3 x ULN, any AST) & severe HD (TB >3 - 10 x ULN, any AST). After calculating the CP score for each patient, the 2 criteria were compared. Results: Conclusions: When assessed with a composite index of TB & AST (NCI-ODWG criteria), normal-to-mild HD correlated with CP group A (where dose modification of chemotherapeutic agents is usually not necessary). Moderate-to-severe HD assessed by TB & AST correlated with CP groups B & C (where dose modification may be necessary). The NCI-ODWG index, using TB & AST, provides a simple & objective way of assessing HD & can be applied in outpatient clinics & clinical trials for dose modification of chemotherapy. In cancer patients, TB is the predominant factor in classifying the severity of HD . (Support: 1UO1-CA099168–01 & NIH/NCCR/GCRC #5M01 RR 00056) No significant financial relationships to disclose.
Incorporation into lipid nanoparticles extends the duration of activity of treprostinil in an acute hypoxia rat model of pulmonary arterial hypertension
Authors: Donna Omiatek, Franziska Leifer, Vladimir Malinin, Jane Ong, Tara Henn, Zhili Li, Richard Chapman, Dan Salvail, Charles Laurent, Walter Perkins
Journal: European Respiratory Journal (2014)

Introduction : Current inhaled therapies for pulmonary arterial hypertension (PAH), such as Tyvaso®, reduce pulmonary arterial pressure but require frequent dosing and are not well tolerated. Inclusion of treprostinil (TRE) into a sustained-release particle for inhalation may reduce dosing frequency and improve tolerability. Here, we describe lipid nanoparticle formulations delivered by inhalation that extend TRE activity.   Methods : Polyethylene glycol (PEG)-lipid coated nanoparticles containing TRE, a cationic lipid, and a lipophilic additive were formed via solvent flash precipitation. The lipid nanoparticle (LNP) preparations were characterized by size, composition, TRE retention, and release kinetics. Activity was assessed  in vitro  in CHO-K1 cells using a pGlosensor TM  assay and  in vivo  in an acute hypoxia rat model of PAH.   Results : Retention of TRE in LNPs was greatest using long-chain cationic lipids. LNPs where the cationic lipid to TRE molar ratio exceeded 2 exhibited higher levels of retention. A gradual increase in cAMP activation of CHO-K1 cells suggested a delayed-release profile. In the hypoxic rat model, the pulmonary vasodilatory activity of inhaled TRE-containing LNPs was extended beyond that of inhaled TRE in solution. To further improve retention, a derivatized TRE prodrug ester made by addition of alkyl chains is proposed.   Conclusion:  Entrapment of TRE in nanoparticles coated with a PEG-lipid extends the therapeutic activity of inhaled drug relative to that observed when treprostinil is administered in solution. Inhalation delivery of such formulations may reduce dosing frequency and improve tolerability.
Transhiatal protrusion of gastric mucosa and recurrent bronchitis/pneumonia in children
Authors: Sawssan Ali, Renaud Menten, Francoise Smets, Veronique Godding
Journal: European Respiratory Journal (2014)

The relationship between transhiatal protrusion of gastric mucosa, acid reflux and recurrent bronchitis/pneumonia in children remains unclear.  We conducted a retrospective study involving 51 children (23 F, 29M, mean age 4,8 ± 2,9 y) with recurrent bronchitis/ pneumonia persisting despite correct symptomatic treatment. All children were evaluated between 2008 and 2013 for hiatus hernia by barium study of the upper gastro intestinal tract (BSUGT) and gastro-esophageal reflux by 24 hours pH metry (pHM).  80 % had normal pHM; 74,5% had transhiatal protrusion of gastric mucosa (15 mild, 23 moderate). 11 % had pathological pHM and protrusion; 17 % had no reflux and normal BSUGT. No correlation was found between frequency of bronchitis/pneumonia, acid reflux and transhiatal protrusion. The severity of protrusion was associated with vomiting (r=0,640, p=0,008); there was a trend for an association with wheezing (r=0,310, p=0,07). No correlation was found between the percentage of acid reflux, vomiting, wheezing, nocturnal or dry cough. All children with protrusion were treated with proton-pump inhibitors (PPI), as were the children with reflux. The frequency of bronchitis /pneumonia decreased after onset of treatment, and this benefit persisted after 11,7 ±2,8 months (6,7 ± 5,7/y before, vs 0,8 ±1,2/y after treatment, p  We conclude that BSUGT is useful in investigating children with recurrent bronchitis/ pneumonia. The frequency of bronchitis/pneumonia in patients with transhiatal protrusion of gastric mucosa decreased after the onset of PPI, even in case of normal pHM.
Association of Ataxia Telangiectasia Mutated (ATM) Gene Mutation/Deletion with Rhabdomyosarcoma – retraction
Authors: Peilin Zhang, Kunjan S Bhakta, Pier Puri, Robert O Newbury, James R Feramisco, Jean Y Wang
Journal: Molecular Cancer (2003)

The corresponding author submitted this article [1] to Molecular Cancer on an assumption that the manuscript had been lost during its previous transmission to Cancer Biology and Therapy. In fact it had been received by that journal and was published there, simultaneously [2]. The authors are therefore retracting the version published in this journal based on the fact that it was initially submitted to the other journal first. The author is deeply sorry for any inconvenience this may have caused to the editorial staff and readers.
Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following standard-dose combination chemotherapy with etoposide, ifosfamide, and cisplatin.
Authors: W Brugger, J Frisch, G Schulz, K Pressler, R Mertelsmann, L Kanz
Journal: Journal of Clinical Oncology (1992)

To combine the benefits of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil recovery and recombinant human interleukin-3 (rhIL-3) on platelet recovery, we applied standard-dose chemotherapy with the combined administration of IL-3 and GM-CSF to investigate their efficacy and toxicity.Thirty-six patients with advanced malignancies were treated with etoposide (VP16) 500 mg/m2, ifosfamide 4 g/m2, and cisplatin 50 mg/m2 (VIP), followed by the sequential administration of IL-3 (days 1 to 5 subcutaneously [SC]) and GM-CSF (day 6 to 15 SC). Control patients received GM-CSF alone or were treated without hematopoietic growth factors.Subcutaneous IL-3 and GM-CSF treatment was well tolerated; low-grade fever (World Health Organization grade 1 to 2) was the only consistent clinical symptom. Neutrophil recovery documented that the duration of neutropenia less than 0.1 x 10(9)/L or less than 0.5 x 10(9)/L was identical in GM-CSF as well as IL-3 and GM-CSF-treated patients, but was shortened significantly when compared with patients who were treated without cytokines. Overall platelet recovery was not different significantly in the three treatment groups. The biologic activity of IL-3 in this cytokine combination was reflected in a variety of effects, which included an increase in basophil and eosinophil counts and the induction of circulating hematopoietic progenitor cells.We conclude that after conventional-dose VIP chemotherapy, a shortened treatment course of IL-3 (5 days) sequentially followed by GM-CSF (10 days) combines the benefits of prolonged single GM-CSF treatment on WBC count recovery in all patients and an accelerated platelet recovery only in some intensively pretreated patients.
Endotracheal Extubation
Authors: Rafael Ortega, Christopher Connor, Gerardo Rodriguez, Caresse Spencer
Journal: New England Journal of Medicine (2014)

Endotracheal extubation should be performed without causing trauma, while maintaining adequate oxygenation and ventilation. The equipment needed to provide suction, ventilation, and reintubation should be readily available. If extubation is judged to be unsafe, the procedure should be postponed and the patient reevaluated. Most complications related to extubation are preventable. Before performing extubation, the clinician must carefully prepare the medical resources needed to address reasonably foreseeable complications. A failed extubation can lead to a precipitous deterioration in the patient's condition, and attempts to improvise solutions under these challenging circumstances are rarely satisfactory.
Changes in Bone Mineral Density of the Proximal Femur and Spine with Aging
Authors: B. L. Riggs, H. W. Wahner, E. Seeman, K. P. Offord, W. L. Dunn, R. B. Mazess, K. A. Johnson, L. J. Melton
Journal: Journal of Clinical Investigation (1982)

We measured bone mineral density (BMD) of the proximal femur, lumbar spine, or both by dual photon absorptiometry in 205 normal volunteers (123 women and 82 men; age range 20 to 92 yr) and in 31 patients with hip fractures (26 women and 5 men; mean age, 78 yr). For normal women, the regression of BMD on age was negative and linear at each site; overall decrease during life was 58% in the femoral neck, 53% in the intertrochanteric region of the femur, and 42% in the lumbar spine. For normal men, the age regression was linear also; the rate of decrease in BMD was two-thirds of that in women for femoral neck and intertrochanteric femur but was only one-fourth of that in women for lumbar spine. This difference may explain why the female/male ratio is 2:1 for hip fractures but 8:1 for vertebral fractures. The standard deviation (Z-score) from the sex-specific age-adjusted normal mean in 26 women with hip fracture averaged -0.31 (P < 0.05) for the femoral neck, -0.53 (P < 0.01) for the intertrochanteric femur, and +0.24 (NS) for the lumbar spine; results were similar for 5 men with hip fractures. By contrast, for 27 additional women, ages 51-65 yr, with only nontraumatic vertebral fractures, the Z-score was -1.92 (P < 0.001) for the lumbar spine. Thus, contrary to the view that osteoporosis is a single age-related entity, our data suggest the existence of two distinct syndromes. One form, "postmenopausal osteoporosis," is characterized by excessive and disproportionate trabecular bone loss, involves a small subset of women in the early postmenopausal period, and is associated mainly with vertebral fractures. The other form, "senile osteoporosis," is characterized by proportionate loss of both cortical and trabecular bone, involves essentially the entire population of aging women and, to a lesser extent, aging men, and is associated with hip fractures or vertebral fractures or both.
Pharmacokinetics in vivo and pharmacodynamics ex vivo/in vitro of meropenem and cefpirome in the Yucatan micropig model: continuous infusion versus intermittent injection
Authors: Hassan Elkhaïli, Jean-Daniel Peter, Davide Pompei, Dominique Levěque, Laurence Linger, Yves Salmon, Julie Salmon, Henri Monteil, François Jehl
Journal: Clinical Microbiology and Infection (1998)
RSV hospitalization in infants with neuromuscular disease in the Canadian registry of palivizumab after prophylaxis (2005-2012)
Authors: Ian Mitchell, Bosco Paes, Abby Li, Krista Lanctôt
Journal: European Respiratory Journal (2013)

OBJECTIVES: Infants with neuromuscular impairment (NMI) at high risk of severe respiratory syncytial virus (RSV) infection;may receive palivizumab.We compared respiratory illness (RIH) and RSV positive hospitalization (RSVH) rates in NMI infants with prophylaxis versus those prophylaxed for standard indications (SD), and other underlying medical disorders (MD) through the Canadian Registry of Synagis®.(CARESS) METHODS: CARESS is a prospective, observational study in 32 sites across Canada for infants with >1 dose of palivizumab prophylaxis in 2005-2012 seasons. Compliance, RI data collected monthly. RESULTS: 13,310 infants in database. 153 had NMI (1.1%), 11239 SD (84.4%), 1918 MD (14.4%). Enrolment age, gestational age, birth weight, proportions of Caucasians, daycare attendance, smoking exposure, siblings, multiple birth, >5 individuals in the household, history of atopy, significantly different (p<0.05) across the three groups. The NMI group received a smaller proportion of expected number of injections than SD or MD (58.8% versus 65.8% and 67.9%, p=0.032).RIH and RSVH prevalence higher in NMI than SD or MD (RIH; 18.3% versus 9.6% and 5.9%, p<0.0005) (RSVH; 5.23% versus 1.56% and 1.21%, p[<0.0005). Cox proportional hazard analysis showed increased risk of RSVH in NMI patients compared to SD (hazard ratio=4.33, 95%CI 1.9-9.7, p<0.0005), after adjusting for covariates (injection compliance, daycare attendance, having siblings, exposure to smoking and crowding). CONCLUSIONS: Infants with NMI were at higher risk of RIH and RSVH compared to SD or MD. These data support palivizumab prophylaxis in NMI, as recommended by international pediatric bodies.
Identification of restriction-fragment-length polymorphisms in genomic DNA of the lesser snow goose (Anser caerulescens caerulescens).
Authors: T W Quinn, B N White
Journal: Molecular Biology and Evolution (1987)

A genomic library of partially EcoRI-digested DNA from the lesser snow goose, Anser caerulescens caerulescens, was constructed in the phage vector Charon 4. Phage containing only unique sequences were identified by screening plaques with 32P-labeled genomic DNA. Restriction-fragment-length polymorphisms (RFLPs) were identified by probing DNA from 11-13 male birds from the breeding colony at La Perouse Bay. Of the 17 probes examined, all detected RFLPs with at least one of EcoRi, HindIII, Msp1, and Taq1. Several of them identified highly variable regions with multiple alleles. These RFLPs are valuable DNA markers that can be used for (1) the examination of DNA variation, relatedness, and genetic distance and (2) assessing paternity and maternity. These data suggest that there are higher levels of variation of DNA sequence in birds than had previously been thought to exist.
Placebo-controlled trial of sucralfate for inhibiting radiation-induced esophagitis.
Authors: W L McGinnis, C L Loprinzi, S J Buskirk, J A Sloan, R G Drummond, A R Frank, T G Shanahan, S P Kahanic, R L Moore, S E Schild, S L Humphrey
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine whether a sucralfate oral solution can prevent/alleviate radiation-induced esophagitis. PATIENTS AND METHODS Patients included on this clinical trial were beginning thoracic radiation therapy to the mediastinum. Following stratification, they were randomized, in a double-blind manner, to receive a sucralfate solution or an identical-appearing placebo solution. Esophagitis was measured by physicians who used standard criteria and also by patients who used short questionnaires completed weekly during the course of the trial. RESULTS A total of 97 assessable patients were entered onto this clinical trial. During the first 2 weeks of the study, two placebo patients (4%) stopped their study medication, compared with 20 sucralfate patients (40%). This was related to substantially increased incidences of gastrointestinal toxicity (58% of sucralfate patients v 14% of placebo patients; P &gt; .0001). There was no substantial benefit from the sucralfate in terms of esophagitis scores. CONCLUSION This oral sucralfate solution does not appear to inhibit radiation-induced esophagitis and is associated with disagreeable gastrointestinal side effects in this patient population.
Biomarkers of asthma severity in the gene environment interaction in respiratory disease (GEIRD) study
Authors: Lucia Calciano, Simone Accordini, Marcello Ferrari, Mario Olivieri, Paolo Degan, Andrea Pasini, Anna Maria Fratta Pasini, Maria Elisabetta Zanolin, Roberto de Marco
Journal: European Respiratory Journal (2014)

Background. There is a need for non invasive and easily measurable biomarkers able to predict the severity of asthma.

Aim . We sought to assess the association between indicators of asthma severity with peripheral blood eosinophils (B-EOS), fractional exaled nitric oxide level (FeNO) and urinary biomarkers of oxidative stress.

Methods . All asthmatic subjects (375) recruited in the GEIRD study were considered. Each subject underwent an accurate clinical interview, lung function test (LF), and measurement of: FeNO (50, 100, 150, and 200 ml/s), B-EOS, and urinary concentrations (creatinine-standardized) of 8-OHdg and 8-isoprostane (ELISA assay).

An asthma severity score (SS) was computed by a multiple correspondence analysis on the basis of self-reported asthma-like symptoms, hospitalization and number of asthma attacks reported in the past year. Spirometric FEV1% predicted and pre-brochodilator FEV1/FVC were used as indicators of lung function.

To study the association of SS and LF indicators with the biomarkers, gamma regression and linear regression models were used respectively, stratifying by corticosteroids treatment.

Results . The preliminary analysis showed that B-EOS was associated with SS and pre-brochodilator FEV1/FVC. Neutrophils were associated only with FEV1% predicted. FeNO200/250 was associated with SS and FEV1/FVC but not with FEV1% predicted. 8-isoprostane was associated with LF indicators.

![Figure][1]  [1]: pending:yes
Inflammatory markers and community acquired pneumonia (CAP): Prognosis analisis and predictive capacity in the short term
Authors: Ana Pando, Belén Prieto, Miguel Ariza, Marta Clemente, Claudia Madrid, Sebastian Gagatek, Herminia Buchelli, Luis Molinos, Pere Casan
Journal: European Respiratory Journal (2013)

Evaluate the correlation between the levels of biomarkers;C-reactive protein (CRP),procalcitonin (PCT), pro-adrenomedullin (MR-proADM);and its short-term change in time with the severity of the CAP and its bad evolution.Methods:Prospective study,we included patients admitted with the diagnosis of CAP in 1 year.2 extractions of peripheral blood were taken from each patient:1 at the time of diagnosis and the other one at 72 hours after admission.Results:65 patients (66.2%male), mean age:72.5±12.Charlson Index:0.88(0-3).2 patients were admitted to the ICU,4 died and 13 had complications in the income.PCT levels were significantly higher in the S.pneumoniae etiology (p=0.013).  The relationship between MR-proADM the day of diagnosis and the prognostic scales in Figure 2.  We find correlation between the levels of pro-ADM and PSI score (R=0.521,p=0.000),and CURB65 grades (R=0.491,p=0.000).Conclusions: MR-ProADM behaves as the best marker of severity.PCT is a useful marker for predicting bacterial etiology.It would be necessary to analyze a larger number of cases to search for a cut-off point of MR-proADM that can determine the bad evolution.
Screening and monitoring of tuberculosis in patients on tumor necrosis factor antagonist therapy
Authors: Serge Borisov, Galina Lukina, Lidia Guntupova, Lydmila Slogotskaya, Yakov Kochetkov
Journal: European Respiratory Journal (2011)

Background: The tumor necrosis factor antagonists (TNF-ant) are high effective agents, but their essential effect is to increase the risk of tuberculosis (TB) development (Solovic I. et al., Eur Respir J 2010; 36:1185-1206).

Aims: To develop the procedure of TB infection screening and monitoring in patients on TNF-ant, adapted to Russian TB situation and feasible.

Methods: 208 adult pts (rheumatoid arthritis - 69, ankylosing spondylitis - 114, psoriatic arthritis – 18, Behcet's disease - 7) before and on TNF-ant were examined. Clinical exam, X-ray (additional CT in any abnormalities), tuberculin skin test (TST) and interferon-g release assays (IGRA) were performed.

Results: In all cases by primary screening active TB was rejected. In 18 pts residual TB changes were obtained, latent TB infection (by TST) was detected in 82 pts. These 100 pts received preventive TB treatment (PT) - isoniasid 0,3 daily for 12 weeks. During the TNF-ant treatment (exam every 6 months) the active TB was excluded by clinical and X-ray exam, apart from 2 pts with passive-detected active pulmonary TB. In both cases active or latent TB was rejected after screening, PT was not administrated and TB look like primary infection. Another problem was to monitor latent TB, when positive TST (in 51 pts) can not be strong argument for re-PT. Positive IGRA were obtained in 12 of these pts (23,5%) and reduced the number of PT quarter.

Conclusion: In countries with high and medium prevalence of TB not only screening before TNF-ant administration is essential. It is necessary to follow up all pts with regular (every 6 months) IGRA, which only can show the initial exacerbation of latent TB infection or new exogenous infection.
Renal Clearance of B-Type Natriuretic Peptide and Amino Terminal Pro-B-Type Natriuretic Peptide
Authors: Roland R.J. van Kimmenade, James L. Januzzi, Jaap A. Bakker, Alphonse J. Houben, Roger Rennenberg, Abraham A. Kroon, Harry J.G.M. Crijns, Marja P. van Dieijen-Visser, Peter W. de Leeuw, Yigal M. Pinto
Journal: Journal of the American College of Cardiology (2009)