tbuckley/cabot-search huggingface dataset:
Clinical audit of the Quebec Sleep Questionnaire in a routine sleep apnoea service
Authors: James Stockley, Theresa McCauley, Liam O'Reilly, Jodie Hunt, Brendan Cooper
Journal: European Respiratory Journal (2012)

Introduction:  We reviewed 2 years of our obstructive sleep apnoea & hypopnoea syndrome (OSAHS) service. The Quebec Sleep Questionnaire (QSQ) was used as a subjective measure of improvement 1  with CPAP. We aimed to see if QSQ reflected symptomatic improvement in treated patients.   Methods:  Referrals undertook history & baseline overnight oximetry (Pulsox 300i, Minolta, Japan). If positive for OSAHS, they undertook an auto-titration and, if beneficial, a trial of CPAP. Of 783 patients, only 155 completed QSQ before & after the CPAP trial. QSQ includes 5 areas; Q1. hypersomnolence, Q2. diurnal symptoms, Q3. nocturnal symptoms, Q4. emotions, Q5. social interactions. An increased score indicated improved symptoms. We compared objective & subjective improvements with CPAP.   Results:  Patients exhibited witnessed apnoeas (68%), snoring (90%), excessive daytime sleepiness (76%) with 56% showing all 3 symptoms. Differences in SpO2 dip rate, Epworth Score (ESS) & QSQ pre- & post-CPAP trial are shown in Table 1. Surprisingly, there was poor correlation between hypersomnolence (Q1) & ESS.   Conclusion:  QSQ correlates with objective improvements in OSAHS & appears to be a reliable subjective measure of symptom improvement. However, there was poor correlation between ESS & hypersomnolence.    1 Lacasse , et al  Thorax  2004; 59: 494-499.
Surfactant Subtype Conversion Is Related to Loss of Surfactant Apoprotein B and Surface Activity in Large Surfactant Aggregates
Authors: ANDREAS GÜNTHER, REINHOLD SCHMIDT, ANDREAS FEUSTEL, UTE MEIER, CAROLINE PUCKER, MONIKA ERMERT, WERNER SEEGER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Conversion of the highly surface-active subtype of pulmonary surfactant known as large surfactant aggregates (LA) to small aggregates (SA) with poor surface activity has recently been shown to occur upon cyclic changes of the air–liquid interface area in vitro. By subjecting pooled rabbit bronchoalveolar lavage fluid (BALF) to this maneuver, we found that conversion of LA to SA was accompanied by a marked decline in the ability of the remaining LA fraction to reduce surface tension by adsorption and during film compression on a pulsating bubble surfactometer. SA obtained by centrifugation of noncycled rabbit BALF had a similar phospholipid (PL) but different neutral lipid (NL) composition than did the LA. Upon cycling, the increased formation of SA obliterated this difference. No substantial difference in the PL, NL, or fatty acid profile of LA was noted before and after cycling. In contrast, the content of surfactant apoprotein-B (SP-B) in the LA decreased dramatically to nearly undetectable levels during the cycling maneuver, and this decline in SP-B content was closely correlated with the decrease in proportional appearance of LA and loss of surface activity of this fraction. Reconstitution of LA with intact SP-B after cycling virtually fully restored the surface activity of this surfactant subtype. When comparing lavage samples from adults with acute respiratory distress syndrome (ARDS; n = 10) with samples from healthy controls (n = 11), we noted a marked reduction of SP-B in the LA fraction. There was a significant correlation between the SP-B content of the LA fraction and the relative percentage of LA in BALF or the lower surface activity of this surfactant subtype. We conclude that an SP-B-related loss of LA integrity and function may substantially contribute to the decline of this surfactant subtype and the loss of its surface activity during cycling in vitro and in clinical ARDS.
Aprepitant/5HT-3 antagonist (EMEND) for the prevention of chemoradiation-induced nausea and vomiting (CRINV) in patients receiving gemcitabine/ 5-FU–based chemoradiation and concurrent upper abdominal radiation for pancreatic cancer
Authors: A. W. Blackstock, M. Aklilu, J. Lovato, L. Degrass, J. Sommer, R. Howerton, G. Mishra, E. Levine, R. McQuellon
Journal: Journal of Clinical Oncology (2009)

e20661 Background: Significant chemoradiation-induced nausea and vomiting (CRINV) occurs in patients (pts) receiving chemoradiation for pancreatic cancer. The aim of this trial was to determine if prophylactic Aprepitant/5HT-3/dexamethasone added to standard chemoradiation resulted in less CRINV when compared to historical controls. Methods: Pts with locally advanced or resected pancreatic cancer received wkly Gemcitabine (200 mg/m2) and continuous infusion 5-fluorouracil (5-FU) or oral capecitabine with concurrent radiation (50.4 Gy). Aprepitant (125 mg p.o.) was given each Monday (day 1) of each week 1 hr before the gemcitabine infusion and on days 2 and 3 (80 mg p.o.) - 1 hour prior to the radiation. A 5HT-3 antagonist was given orally 30–60 minutes prior to the chemotherapy and dexamethasone (12 mg) was given on day 1 and repeated at a dose of 8 mg on days 2 and 3 with the aprepitant. Grade III/IV nausea was assessed using NCI CTC v. 3.0. The Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) questionnaire was completed at baseline prior to the start of all therapy, Time 1 (T#1), repeated at the end of the first week (T#2) and then repeated again at the end of the last full week of chemoradiation (T#3). Results: Of the 17 patients available for analysis, CTC grade III nausea and grade IV vomiting was observed in one patient (6%) during the entire treatment course. Utilizing the MAT at T#1, T#2 and T#3 respectively; 3/15, 4/15 and 2/13 pts reported experiencing any level of nausea. At those same time points; 0/15, 1/15 and 0/13 pts reported vomiting. The range of the average degree of nausea reported on a scale from 1–10 (worst) was 2.5 -3.67 over the study period. During treatment, 54–64% of participants reported no nausea/vomiting (N/V). For those patients who experienced N/V, it was rated as mild to moderate with only 3 of 17 requiring additional anti-emetics. Conclusions: Prophylactic Aprepitant/5HT-3/dexamethasone therapy resulted in minimal CRINV for pts receiving upper abdominal chemoradiation in this feasibility study. This regimen may be soon be integrated in to future CALGB pancreatic chemoradiation trials. [Table: see text]
Effects of low- vs high-dose fluticasone/formoterol combination therapy on AMP challenge in asthmatic patients
Authors: Frank Kanniess, Zuzana Diamant, Mark Lomax, Meena Jain
Journal: European Respiratory Journal (2013)

Background:  The ICS fluticasone propionate (FLUT) and the LABA formoterol fumarate (FORM) have now been combined in a single aerosol inhaler (FLUT/FORM;  flutiform ®). The effect of low- (2 puffs 50/5µg bid) vs high-dose (2 puffs 250/10µg bid) FLUT/FORM on airway responsiveness to AMP was compared in an incomplete block, placebo-controlled, 2-way crossover study.  Post hoc  data analysis from patients who received both FLUT/FORM doses is presented.   Methods:  62 patients (33M, 29F; ≥18yrs; reversible FEV 1  ≥60% pred.) discontinued maintenance ICS medication for 2-3wks; those showing a provocative dose of AMP producing a 20% decline in FEV 1  (AMP PD 20  FEV 1 ) of  20  FEV 1  (day 1 vs day 28) between treatments were compared by an ANCOVA.   Results:  15 patients were randomised to receive both high- and low-dose FLUT/FORM. The change in AMP PD 20  FEV 1  was greater with FLUT/FORM high- compared with low-dose (LS means: high dose = 11mg; 95% CI 4.3, 27.9; low dose = 4.6mg, 95% CI 1.8, 11.8), with a statistically significant 2.4 fold difference in AMP PD 20  FEV 1  (1.2 doubling doses) between doses (LS mean: 2.4; 95% CI 1.3, 4.5; p=0.012). FLUT/FORM was well-tolerated; only few (mild or moderate) AEs occurred.   Conclusions:  A significant dose-response was found between low- and high-dose FLUT/FORM with the higher dose demonstrating a greater reduction in airway responsiveness to AMP.
Five Different Adenomas Derived From the Rat Adenohypophysis: Immunocytochemical and Ultrastructural Study2, 3
Authors: Donna J. McComb, Nancy Ryan, Eva Horvath, Kalman Kovacs, Eva Nagy, Istvan Berczi, Istvan Domokos, Ferenc A. Laszlo
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Five Different Adenomas Derived From the Rat Adenohypophysis: Immunocytochemical and Ultrastructural Study, Get access Donna J. McComb, Donna J. McComb Search for other works by this author on: Oxford Academic PubMed Google Scholar Nancy Ryan, Nancy Ryan Search for other works by this author on: Oxford Academic PubMed Google Scholar Eva Horvath, Eva Horvath Search for other works by this author on: Oxford Academic PubMed Google Scholar Kalman Kovacs, Kalman Kovacs Search for other works by this author on: Oxford Academic PubMed Google Scholar Eva Nagy, Eva Nagy Search for other works by this author on: Oxford Academic PubMed Google Scholar Istvan Berczi, Istvan Berczi Search for other works by this author on: Oxford Academic PubMed Google Scholar Istvan Domokos, Istvan Domokos Search for other works by this author on: Oxford Academic PubMed Google Scholar Ferenc A. Laszlo Ferenc A. Laszlo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 6, June 1981, Pages 1103–1111, https://doi.org/10.1093/jnci/66.6.1103 Published: 01 June 1981 Article history Received: 16 May 1980 Revision received: 22 October 1980 Accepted: 14 November 1980 Published: 01 June 1981
Abstract 16634: p300 is Required for the DNA Damage Response Through Acetylation of Histone H3K56
Authors: Sumit Jain, JianQin Wei, Claudia O Rodrigues, Nanette H Bishopric
Journal: Circulation (2011)

Background: The nuclear acetyltransferase p300 is a chromatin-modifying enzyme that programs gene expression in response to extracellular and intracellular signals. p300 has been implicated in tran...
Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial
Authors: Alan K Burnett, Nigel H Russell, Robert K Hills, David Bowen, Jonathan Kell, Steve Knapper, Yvonne G Morgan, Jennie Lok, Angela Grech, Gail Jones, Asim Khwaja, Lone Friis, Mary Frances McMullin, Ann Hunter, Richard E Clark, David Grimwade
Journal: The Lancet Oncology (2015)
Lesson of the Week: Insulin dependent diabetes in nonagenarians
Authors: N. D C Sturrock, S. R Page, P. Clarke, R. B Tattersall
Journal: BMJ (1995)

prostatic obstruction.Altemative techniques will be developed and may eventually come to supplant transurethral resection of the prostate.However, until adequate information on the effect of new treatments with respect to relief of obstruction, short term and long term morbidity, mortality, cost effectiveness, quality of life, and reoperation rate is available, these techniques should be regarded as experimental.1 Kirby RS, Bishop MC.Are the days of transurethral resection of prostate for benign prostatic hyperplasia numbered?
Systemic lupus erythematosus (SLE): Cyto- and chemokines as possible serum markers for pulmonary involvement?
Authors: Johannes Streitzig, Zsoka Weiszhar, Christine Balogh, Andras Bikov, Krisztina Vincze, Lilla Tamasi, Ildiko Horvath, Veronika Muller
Journal: European Respiratory Journal (2012)

SLE is a systemic autoimmune disease associated with high prevalence of lung involvement. Pulmonary manifestations (PM) in SLE are difficult to diagnose and the ability of its detection with serum markers could be useful for early detection and specific treatment.  Twenty three patients with SLE (age: 45.4±14.6 years; 22 female, 10 smokers) were enrolled in pulmonary examination including physical examination, chest X-ray, lung function test, CO diffusion capacity (DLCO) measurement and blood gas analysis. Plasma of 17 patients was analyzed by protein array system with chemiluminescence imaging, including the cytokines and chemokines: 4-1BB, IP-10, IL-12 p70, IL-17, CCL14a, CCL21, CCL28, MCP-1, MCP-4, I-TAC.  PM was diagnosed in 12 patients (52.2%; age:41.3±14.2 years), including pulmonary fibrosis (3), shrinking lung syndrome (1) and ventilatory disorder (8). Eleven patients had no PM (47.8%; age:50.0±12.1 years). In patients with PM significant decrease of static lung volumes and DLCO were noted (TLC % pred): 81.1± 3.4 vs. 93.7± 3.9 p  In lupus patients PMs are prevalent and are associated with decreased lung volumes and DLCO. Microarray results identified CCL21 and MCP1, IP10 as potential candidates for further analysis of PM in SLE patients.
Abstract 8449: Evaluation of Atrial Remodeling and Fibrillation Vulnerability Using Molecular Imaging of Matrix Metalloproteinases
Authors: Ben A Lin, Joseph G Akar, Rupak Mukherjee, Kailasnath Purushothaman, Shaina R Eckhouse, Chi Liu, Xenophon Papademetris, Donald P Dione, Francis G Spinale, Albert J Sinusas
Journal: Circulation (2011)

INTRODUCTION: Heart failure after myocardial infarction (MI) leads to atrial remodeling and fibrosis, thereby increasing vulnerability to atrial fibrillation (AF). While matrix metalloproteinase (MMP) activity is known to be an important mediator of left ventricular (LV) remodeling after MI, atrial MMP activation in this setting has not been well studied. HYPOTHESIS: We hypothesized that atrial structural remodeling and fibrillation vulnerability occurring early after MI can be noninvasively assessed using targeted molecular imaging of MMP activation. METHODS: In vivo and ex vivo SPECT/CT images were obtained in control pigs (n=7) and in pigs 1 week (n=2) or 4 weeks (n=6) after surgical induction of MI. Hybrid 64-slice SPECT/CT scans were performed at 2 hours after intravenous injection of a Tc99m-labeled radiotracer targeted to activated MMPs (RP805; Lantheus Medical Imaging, North Billerica, MA). Myocardial RP805 retention was quantified by gamma well counting after sacrifice. AF vulnerability was assessed in control pigs (n=3) and in pigs 4 weeks post-MI (n=4) using atrial burst pacing for 10 seconds with cycle lengths ranging from 300 to 180 ms. RESULTS: SPECT/CT images demonstrated increased uptake in the MI region and both atria compared to control pigs. In vivo images at 1 week post-MI are shown. RP805 retention at 1 week post-MI was 762±75% in the MI region compared to normal LV and 339±52% in the left atrium (LA) compared to normal LA (p&lt;0.01 each). At 4 weeks post-MI, these values were 351±51% in the MI region and 174±27% in the LA (p&lt;0.01 each). AF was inducible in 4 of 4 post-MI pigs and 0 of 3 controls (p=0.03). CONCLUSIONS: MMP-targeted SPECT/CT imaging may provide valuable noninvasive assessment of atrial remodeling and allow early identification of arrhythmogenic substrates prior to the onset of irreversible fibrosis. This approach may have significant implications regarding AF risk stratification as well as preventive and interventional AF treatment.
Mutations in AEC syndrome skin reveal a role for p63 in basement membrane adhesion, skin barrier integrity and hair follicle biology
Authors: S.E. Clements, T. Techanukul, J.E. Lai-Cheong, J.B. Mee, A.P. South, C. Pourreyron, N.P. Burrows, J.E. Mellerio, J.A. McGrath
Journal: British Journal of Dermatology (2012)

Background AEC (ankyloblepharon–ectodermal defects–clefting) syndrome is an autosomal dominant ectodermal dysplasia disorder caused by mutations in the transcription factor p63. Clinically, the skin is dry and often fragile; other features can include partial eyelid fusion (ankyloblepharon), hypodontia, orofacial clefting, sparse hair or alopecia, and nail dystrophy. Objectives To investigate how p63 gene mutations affect gene and protein expression in AEC syndrome skin. Methods We performed microarray analysis on samples of intact and eroded AEC syndrome skin compared with control skin. Changes were verified by quantitative real‐time reverse transcription–polymerase chain reaction and, for basal keratinocyte‐associated genes, by immunohistochemistry and analysis of microdissected skin. Results We identified significant upregulation of six genes and downregulation of 69 genes in AEC syndrome skin, with the main changes in genes implicated in epidermal adhesion, skin barrier formation and hair follicle biology. There was reduced expression of genes encoding the basement membrane proteins FRAS1 and collagen VII, as well as the skin barrier‐associated small proline‐rich proteins 1A and 4, late cornified envelope protein 5A, hornerin, and lipid transporters including ALOX15B. Reduced expression of the hair‐associated keratins 25, 27, 31, 33B, 34, 35, 81 and 85 was also noted. We also confirmed similar alterations in gene expression for 26 of the 75 genes in eroded AEC scalp skin. Conclusions This study identifies specific changes in skin structural biology and signalling pathways that result from mutant p63 and provides new molecular insight into the AEC syndrome phenotype.
Abstract 278: Diet-Induced Leukocyte Telomere Shortening Correlates with Extent of Atherosclerosis
Authors: GENESIO KARERE, Shifra Birnbaum, Clint Christensen, Michael Mahaney, John VandeBerg, Laura Cox
Journal: Circulation Research (2014)

Introduction: Cardiovascular disease, the leading cause of death in developed countries, is commonly due to atherosclerosis. Studies have demonstrated association between leukocyte telomere shortening (LTS), extent of atherosclerotic lesions and accelerated cell senescence. Further LTS is associated with dietary intake. However, efforts to link LTS, diet and extent of lesions have been unsuccessful in humans due to difficulties controlling diet in large human population studies. To begin addressing these critical issues, we controlled dietary fat (high-fat, HF) in baboons for 2yrs - a well-developed primate model of human atherosclerosis. This is the first study in primates showing correlation of LTS with both chronic HF diet and atherosclerotic lesions. Hypothesis: We hypothesized that leukocyte telomere length decreased with chronic HF diet in baboons and is correlated with extent of atherosclerotic lesions. Methods and Results: A cohort of pedigreed baboons (n=107; females=46, males=61) was fed a HF diet for 2yrs. Absolute leukocyte telomere lengths (LTL; kb/diploid genome) were quantified by qPCR before and after diet challenge. Total telomere length was calculated by computing the ratio of telomere quantity per single copy gene quantity (baboon LIPG). Mean LTL was significantly shorter after feeding baboons a HF diet for 2 yrs (paired t test, p=0.03). Baboons (n=232) maintained on a low fat diet for 2yrs showed no significant difference in LTL (p=0.47). These findings suggest that a HF diet accelerates LTS. Further we quantified the extent of atherosclerotic lesions in baboons after 2yr HF diet and found that LTL, adjusted for age and sex, were correlated with lesions in descending aorta (Pearson correlation, r=0.19; p=0.03). Interestingly this correlation was significant in females but not in males after adjusting for age (r=0.27, p=0.03). Conclusions: LTS correlates with chronic feeding with a HF diet in baboons, is significantly correlated with arterial lesions and the correlation is sex-specific. These findings suggest that LTS may be a potential biomarker of extent of atherosclerosis.
The Prospective Study of S-1 + Gemcitabine and Concurrent Radiotherapy for Unresectable Locally Advanced Pancreatic Cancer
Authors: Tetsuo Kimura, Takahiro Goji, Jinsei Miyoshi, Yasuteru Fujino, Shinji Kitamura, Momoko Sato, Masako Kimura, Hiroshi Miyamoto, Naoki Muguruma, Tetsuji Takayama
Journal: Annals of Oncology (2014)
Complete Surgical Excision Is Effective Treatment for Children With Immature Teratomas With or Without Malignant Elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study
Authors: Neyssa M. Marina, Barbara Cushing, Roger Giller, Lewis Cohen, Stephen J. Lauer, Arthur Ablin, Robert Weetman, John Cullen, Paul Rogers, Charles Vinocur, Charles Stolar, Fred Rescorla, Edith Hawkins, Stephen Heifetz, Pejaver V. Rao, Mark Krailo, Robert P. Castleberry
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine whether the 3-year event-free survival (EFS) of children with completely resected immature teratomas is greater than 85%. PATIENTS AND METHODS: Patients with immature teratomas treated at Pediatric Oncology Group or Children's Cancer Group institutions were eligible. Pathology was centrally reviewed to confirm diagnosis and tumor grading. Follow-up included physical examination, measurement of tumor markers (alpha fetoprotein and human chorionic gonadotropin), and imaging. All patients were monitored for events, defined as tumor recurrence, second malignancy, or death. RESULTS: Seventy-three children (median age, 7.8 years) with extracranial immature teratomas were enrolled on study. Primary tumor sites included ovarian (n = 44), testicular (n = 7), and extragonadal (n = 22). However, on review, 23 patients had foci of yolk sac tumor (n = 21) or primitive neuroectodermal tumor (n = 2), whereas 50 had pure immature teratomas. Twenty-five patients had increased alpha fetoprotein (n = 18), human chorionic gonadotropin (n = 5), or both (n = 2); nine had foci of yolk sac tumor on review. Pathology review identified 23 patients with grade 1, 29 with grade 2, and 21 with grade 3 immature teratomas. With a median follow-up of 35 months, the overall 3-year EFS was 93% (95% confidence interval, 86% to 98%), with 3-year EFS of 97.8%, 100%, and 80% for patients with ovarian, testicular, and extragonadal tumors, respectively. Only four of 23 patients with immature teratoma and malignant foci developed recurrence, suggesting that surgical resection followed by close observation are effective treatment. Overall, five patients had disease recurrence 4 to 7 months from diagnosis, and four (80%) are disease free after platinum-based therapy. The fifth patient has residual tumor after cisplatin, etoposide, and bleomycin treatment requiring further therapy. CONCLUSION: Surgical excision is safe and effective treatment for 80% to 100% of children with immature teratoma.
Risk factors for obstructive lung function in morbidly obese patients
Authors: Astrid van Huisstede, Jan Willem Elte, Guido Mannaerts, Eric Snoey, Ronald Luitwieler, Erwin Birnie, Pieter Hiemstra, Gert-Jan Braunstahl
Journal: European Respiratory Journal (2011)

Background: Morbidly obese patients are not only at risk for asthma but also for pulmonary complications related to bariatric surgery.

Aim of the study: To calculate a risk score for obstructive lung function in morbidly obese patients as pre-surgical screening tool before bariatric surgery, and relating pulmonary complications to this score.

Methods: 39 of the 342 patients (11.4%) had an obstructive lung function. A history of asthma (adj.OR 3.2; 95%CI:1.4-7.5), >5 pack years (adj.OR 2.8; 95%CI:1.2-6.3) and abdominal circumference >120cm (adj.OR 7.0; 95%CI:1.6-31.0) were associated with an obstructive lung function (multiple logistic regression). The risk of obstructive lung function was calculated (1, 1 and 2 points respectively). At the cut of point of ≥2 sensitivity was 0.968 and specificity 0.315 (ROC analysis, area under the curve 0.764). Inhalation medication after pulmonary screening was prescribed in 35 patients, of whom 34 (97%) had a risk-score of ≥2 (p<0.000). Only 5 pulmonary complications occurred, however all pulmonary complications were in risk-score ≥2 group (p=0.325).

Conclusion: Abdominal circumference is a better predictor than BMI for obstructive lung function in morbidly obese patients undergoing bariatric surgery. Although the incidence of pulmonary complications after bariatric surgery is low, pre-surgical risk factor analysis could identify patients at risk for obstructive lung function and pulmonary complications.