tbuckley/cabot-search huggingface dataset:
Assessment of sleep disturbance during recovery from acute exacerbations of COPD (AECOPD)
Authors: Eui-Sik Suh, Michelle Ramsay, Swapna Mandal, Rachel Harding, John Moxham, Nicholas Hart
Journal: European Respiratory Journal (2014)

Background  Sleep disturbance is a common feature of COPD, yet there are limited data demonstrating the changes in sleep quality following AECOPD. We hypothesised that sleep quality would improve from admission to discharge and up to 28 days after hospital discharge.   Methods  Patients with AECOPD admitted to a UK university hospital were issued with an accelerometer  (Actiwatch Spectrum, Philips Respironics, PN, USA)  during admission and for 4 weeks post - discharge. Total sleep time (TST), wake time after sleep onset (WASO) and sleep efficiency (SE) were analysed on nights 0, 1 and 2 of the inpatient stay, and on the night before discharge, for those who were inpatients for ≥3 nights. FEV 1  and inspiratory capacity (IC) were measured daily in hospital. The mean of 7 night measurements during weeks 1 and 4 post-discharge were compared. Readmissions or emergency department (ED) attendances within 28 days of discharge were prospectively recorded.   Results  28 patients had ≥3 nights of inpatient data (72±10years, 46% male, FEV 1  27±11%). TST, WASO and SE did not improve during the hospital stay, and were not correlated with FEV 1  or IC. 33 patients had 4 weeks of sleep data post-discharge (67±7years, 45% male, FEV 1  26±10%). Sleep measures did not improve between weeks 1 and 4. Sleep quality in week 1 was impaired in 5 patients (15%) who were readmitted or attended the ED within 28 days (SE 56±18%  vs  73±13%, p=0.03; TST 266±87mins  vs  375±92mins, p=0.03).   Discussion  Sleep quality did not improve during hospital admission or within the first month post discharge. In a small sample, sleep quality was impaired in week 1 following discharge in patients who were readmitted or attended the ED within 28 days.
Characteristics of patients with pulmonary hypertension in end stage renal disease
Authors: Matthias Held, Tobias Freund, Josef Zimmermann, Berthold Jany
Journal: European Respiratory Journal (2014)

Introduction and background: In patients with end-stage renal disease (ESRD) and patients on hemodialysis pulmonary hypertention (PH) has been reported. PH is generally mild and the underlying mechanisms remain unclear. Most reports are based on echocardiographic data.  Aims and objectives: To characterize patients with pulmonary hypertension on hemodialysis and identify influencing mechanisms.  Methods: We prospectively studied patients with end stage renal disease on hemodialysis including echocardiography, laboratory tests, ECG, bodyplethysmography, six minute walking test and cardiopulmonary exercise test. If echocardiography showed PH, a right heart catheterization was performed.  Results: In the cohort of 41 patients (63 % male/27% female, BSA 1.8, BMI 26) we found pulmonary hypertension in 17 patients, 24 patients had no signs of PH. Patients with pulmonary hypertension showed significantly more frequently atrial fibrillation (59/13 %, p  p  p  p   Conclusion:The higher incidence of atrial fibrillation in the PH group may either indicate pulmonary venous hypertension or reflect a complication of PH. The lower serum creatinine levels might reflect a more intensive dialysis regimen to manage volume overload or be a consequence of a reduced muscle mass indicating renal cachexia in patients with ESRD and PH. Although NT-pro-BNP-serum levels are affected by impaired renal function itself, levels above 8500 pg/ml may indicate PH. The role of elevated parathormone levels in patients with PH remains unclear.
Cough and expiratory reflex during growth in young rabbits
Authors: Laurianne Coutier, Bruno Demoulin, Claude Bonabel, Cyril Schweitzer, François Marchal, Silvia Varechova
Journal: European Respiratory Journal (2014)

Rationale:  Cough is rarely reported during neonatal period in healthy newborns but it is the most frequent respiratory symptom in the first months of life. Consistently, studies on the maturing newborns of different animal species have shown that cough reflex (CR) from larynx is absent at birth and develops over a span of 2-3 weeks, whereas expiration reflex (ER) is already present at birth. This suggests that CR and ER may undergo a maturational process during childhood.   Objective:  To study the incidence, stimulus threshold and type of defensive response from tracheobronchial region to mechanical stimulation in young rabbits at different ages.   Methods:  Forty three rabbits (7 days n=8, 15 days n=5, 30 days n=17, 90 days n=13) underwent a discrete mechanical challenge of trachea (50 – 2400 ms) during pentobarbital anesthesia.   Results:  Both CR and ER were present by 7 days post natal age. However, the incidence of expiration reflex was significantly higher at 15th day (72%) compared to 30th day (18%) and 90th day (42%) (p   Conclusion:  Our results have shown differences in CR and ER incidence during aging pointing to the maturational process of respiratory defensive responses. In younger animals, most responses are ER and the incidence of CR is low. Based on the assumption that the afferent pathway is similar for ER and CR, the current findings support neuronal plasticity of brainstem cough centre as a mechanism of CR maturation during early development.
Commensal-pathogen interactions in the intestinal tract
Authors: Lisa A Reynolds, Katherine A Smith, Kara J Filbey, Yvonne Harcus, James P Hewitson, Stephen A Redpath, Yanet Valdez, María J Yebra, B Brett Finlay, Rick M Maizels
Journal: Gut Microbes (2014)

The intestinal microbiota are pivotal in determining the developmental, metabolic and immunological status of the mammalian host. However, the intestinal tract may also accommodate pathogenic organisms, including helminth parasites which are highly prevalent in most tropical countries. Both microbes and helminths must evade or manipulate the host immune system to reside in the intestinal environment, yet whether they influence each other’s persistence in the host remains unknown. We now show that abundance of Lactobacillus bacteria correlates positively with infection with the mouse intestinal nematode parasite, Heligmosomoides polygyrus, as well as with heightened regulatory T cell (Treg) and Th17 responses. Moreover, H. polygyrus raises Lactobacillus species abundance in the duodenum of C57BL/6 mice, which are highly susceptible to H. polygyrus infection, but not in BALB/c mice, which are relatively resistant. Sequencing of samples at the bacterial gyrB locus identified the principal Lactobacillus species as L. taiwanensis, a previously characterized rodent commensal. Experimental administration of L. taiwanensis to BALB/c mice elevates regulatory T cell frequencies and results in greater helminth establishment, demonstrating a causal relationship in which commensal bacteria promote infection with an intestinal parasite and implicating a bacterially-induced expansion of Tregs as a mechanism of greater helminth susceptibility. The discovery of this tripartite interaction between host, bacteria and parasite has important implications for both antibiotic and anthelmintic use in endemic human populations.
Radiofrequency Ablation of Atrial Fibrillation in Patients With Mechanical Mitral Valve Prostheses
Authors: Ayman A. Hussein, Oussama M. Wazni, Serge Harb, Lee Joseph, Mohammed Chamsi-Pasha, Mandeep Bhargava, David O. Martin, Thomas Dresing, Thomas Callahan, Mohamed Kanj, Andrea Natale, Bruce D. Lindsay, Walid I. Saliba
Journal: Journal of the American College of Cardiology (2011)
Pharmacokinetic profile of fentanyl sublingual (SL) spray
Authors: E. G. Feigal, N. Parikh, G. Kottayil, D. Fisher
Journal: Journal of Clinical Oncology (2008)

13505 Background: Fentanyl sublingual (SL) spray is formulated to enhance the rate and extent of fentanyl absorption across the sublingual mucosa. This new formulation is being developed for management of breakthrough pain in cancer patients who are already receiving and are tolerant to opioid therapy for their underlying, persistent, cancer-related pain. The formulation is administered under the tongue using an oral spray device. Methods: A single dose, randomized, 5-treatment, 5-period crossover study of fentanyl SL spray was conducted under fasted conditions in healthy subjects. The objectives were to determine the pharmacokinetics of 5 different doses (100 - 800 μg, Part A) and to assess the impact of temperature (cold beverage, hot beverage) and pH (oral bicarbonate solution; oral carbonate beverage) in the oral cavity on relative bioavailability at a fixed dose (Part B). Subjects had to meet pre-specified eligibility criteria. Dosing days were separated by a washout period of ≥ 7 days. Naltrexone 50 mg was given orally pre/post each treatment to attenuate opioid effect. Plasma samples were obtained before and 5, 10, 20, 30, 40 min, 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, 24 and 36 h post-dose and analyzed for fentanyl using a validated LC-MS-MS procedure. LLOQ was 25 pg/ml. Results: 53 subjects enrolled in part A. Cmax and AUC were dose-proportional over the range of doses. Fentanyl Cp increases rapidly following administration, initially detected at 5 min, reaching 61% of Cmax by 10 min and 87% of Cmax by 20 min post dose. Fentanyl Cp showed a long plateau: Cp was ≥ 80% of Cmax for ∼ 2 hours. 14 subjects enrolled in part B. Varying pH and temperature of the oral cavity did not affect AUC or Cmax. No SAEs were noted. In Part A, AEs were observed in 31 subjects; 46 AEs were probably related to study treatment and 29 were possibly related. In Part B, AEs were observed in 9 subjects: 7 AEs were probably related to study treatment and 17 were possibly related. AEs were emesis or nausea. Conclusion: Results of this study support the decision to proceed with development of this product for patients with breakthrough pain. Dose proportionality and lack of effect of pH and temperature indicate that dosing will be predictable, facilitating titration. Phase 3 trials assessing efficacy and safety in patients with breakthrough cancer-related pain are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Insys Therapeutics Insys Therapeutics Insys Therapeutics Insys Therapeutics
Immune Response to a Transplantable Malignant Melanoma in Mice2
Authors: W. N. Bartholomaeus, A. E. Bray, J. M. Papadimitriou, D. Keas
Journal: JNCI Journal of the National Cancer Institute (1974)

Humoral immune response to the B16 melanoma in its syngeneic host, the C57BL/6J mouse, in volved production of complement-fixing, cytotoxic, and reaginic antibodies to B16 antigens. Lymphocytes that were stimulated to DNA synthesis when cultured with B16 antigens were present in the spleen and regional lymph nodes. Lymphocytes capable of inhibiting B16 growth in vitro were in the spleen but not in the regional lymph nodes during tumor growth; in contrast, lymphocytes of the regional nodes stimulated B16 growth in vitro. Serum collected during tumor growth converted from inhibitory to stimulatory the action of immune spleen lymphocytes on 816 growth. Macrophages in the tumor increased in number during tumor growth; histopathologic examination of the growing tumor revealed an early, transient, lymphocyte infiltrate and later macrophage involvement. The blood, spleen, and regional-node lymphocyte response to phytohemagglutinin decreased as the tumor grew. We concluded that absence of cytotoxic lymphocytes in the regional nodes, serum-mediated conversion of the effect of immune lymphocytes from inhibitory to stimulatory action on B16 growth, and anergy ofthymus-derived lymphocytes allowed the B16 tumor success over its host.
Abstract 1176: Exercise Training and Heart Failure: Will Patients Feel Better If They Exercise?
Authors: Lorraine Evangelista, Michele A Hamilton, Gregg C Fonarow, Kathleen Dracup
Journal: Circulation (2009)

BACKGROUND: The beneficial effects of exercise training on mood disorders and quality of life (QOL) in patients with heart failure (HF) remains controversial, with investigators documenting both po...
Phase I Study in Advanced Cancer Patients of a Diversified Prime-and-Boost Vaccination Protocol Using Recombinant Vaccinia Virus and Recombinant Nonreplicating Avipox Virus to Elicit Anti–Carcinoembryonic Antigen Immune Responses
Authors: John L. Marshall, Robert J. Hoyer, Mary Ann Toomey, Kristen Faraguna, Ping Chang, Ellen Richmond, James E. Pedicano, Edmund Gehan, Ronald A. Peck, Philip Arlen, Kwong Y. Tsang, Jeffrey Schlom
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This trial sought to determine, for the first time, the validity in human vaccinations of using two different recombinant vaccines in diversified prime-and-boost regimens to enhance T-cell responses to a tumor antigen. PATIENTS AND METHODS: Eighteen patients with advanced tumors expressing carcinoembryonic antigen (CEA) were randomized to receive either recombinant vaccinia (rV)-CEA followed by three avipox-CEA vaccinations, or avipox-CEA (three times) followed by one rV-CEA vaccination. Subsequent vaccinations in both cohorts were with avipox-CEA. Immunologic monitoring was performed using a CEA peptide and the enzyme-linked immunospot assay for interferon gamma production. RESULTS: rV-CEA followed by avipox-CEA was superior to the reverse order in the generation of CEA-specific T-cell responses. Further increases in CEA-specific T-cell precursors were seen when local granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose interleukin (IL)-2 were given with subsequent vaccinations. The treatment was extremely well tolerated. Limited clinical activity was seen using vaccines alone in this patient population. Antibody production against CEA was also observed in some of the treated patients. CONCLUSION: rV-CEA was more effective in its role as a primer of the immune system; avipox-CEA could be given up to eight times with continued increases in CEA T-cell precursors. Future trials should use rV-CEA first followed by avipox-CEA. Vaccines specific to CEA are able to generate CEA-specific T-cell responses in patients without significant toxicity. T-cell responses using vaccines alone may be inadequate to generate significant anticancer objective responses in patients with advanced disease. Cytokines such as GM-CSF and IL-2 may play a key role in generating such responses.
Statistical Analysis of Cytogenetic Data in Cervical Neoplasia
Authors: K. M. Cellier, J. A. Kirkland, M. A. Stanley
Journal: JNCI Journal of the National Cancer Institute (1970)

Chromosome counts obtained from 156 patients with carcinoma of the cervix in Adelaide, South Australia, were statistically analyzed. Most carcinomas (80%) had counts derived from 2 or more ploidy classes, and a statistical method for classifying the lesions into the number and type of ploidy class was derived by use of a theoretical model for the distribution of chromosome counts. Each carcinoma was described in terms of estimates of the 2 parameters, the mean (x) and the variance (s2). Allocation of carcinomas to particular classes was generally straightforward. Examining the scatter diagram obtained by plotting the variance (y) against the mean (x) for each case revealed a change in the distribution of chromosome counts when the disease progressed from carcinoma in situ to invasive carcinoma. Carcinomas consisting of diploid-triploid-tetraploid counts at the in situ phase apparently changed to one of 3 classes: (a) triploid dominance in the diploid-triploid-tetraploid class, (b) diploid dominance in the diploid-triploid or diploid-tetraploid classes, or (c) triploid dominance in the triploid-tetraploid class. However, carcinomas in situ consisting of triploid-tetraploid-qulntuploid counts (all mixed- or largecelled types) were not represented in the invasive carcinomas. The implications of these results are discussed.
Do changes in body mass index explain temporal trends in prevalence of wheeze and asthma
Authors: Myrofora Goutaki, Parvinder Singh, Spycher Ben, Dogaru Cristian, Pescatore Anina, Baeuml Jennifer, Beardsmore Caroline, Kuehni Claudia
Journal: European Respiratory Journal (2013)

Aims  The reported associations between asthma and obesity, and the increasing prevalence of both conditions over time suggest that changes in body mass index (BMI) might help explaining the increase in prevalence of wheeze in children. We tested this hypothesis in two population-based cohort studies conducted 8 years apart with identical methodology.  Methods  We assessed prevalence of wheeze in two cohorts of 1-4 year old white children in 1990 (N=1153) and 1998 (N=2089) respectively, using identical questionnaires. Height and weight were measured independently by health visitors. We used multivariable logistic regression to calculate odds ratios (OR) for trends in current wheeze (CW) and doctor diagnosed asthma (DDA), controlling for confounders, with and without adjustment for BMI z-scores (WHO child growth standards)  Results  Between 1990 and 1998 BMI z-scores increased slightly (-0.07 to 0.10, p  Conclusions  In our study, trends in BMI did not help to explain the marked increase in prevalence of asthma and wheezing illness.  Funding  SNF PDFMP3-123162; SNF 32003B-144068; Asthma UK 07/048.
Factors associated with clinical and virological response in patients treated with oseltamivir or zanamivir for influenza A during the 2008–2009 winter
Authors: T. Blanchon, F. Mentré, C. Charlois-Ou, Q. Domic, A. Mosnier, M. Bouscambert, F. Carrat, X. Duval, V. Enouf, C. Leport, None Bivir Study Group
Journal: Clinical Microbiology and Infection (2011)
Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development
Authors: D.H. Siegel, J.A. Mann, A.L. Krol, K.A. Rauen
Journal: British Journal of Dermatology (2011)

The RASopathies are a class of human genetic syndromes caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Costello syndrome (CS) is a RASopathy caused by mutations in the HRAS gene, a key regulator of signal transduction.To quantify the specific cutaneous phenotype observed in 46 individuals with Costello syndrome with confirmed HRAS mutations.This was a cross-sectional study. Dermatological surveys were designed by the authors and were completed by parents of mutation-positive individuals with CS at the Costello Syndrome Family Network (CSFN) conferences in 2007 and 2009. Dermatological examinations were performed by the authors at the CSFN conferences.Cutaneous papillomas were reported in 33 of the 46 (72%) participants, with age of onset ranging from infancy to 22years. Individuals with CS are more likely than patients with cardiofaciocutaneous syndrome (CFC) to present with cutaneous papillomas (72% vs. 5%, P<0·001) and palmoplantar keratoderma (76% vs. 36%, P<0·001). Individuals with CS are less likely than individuals with CFC to present with sparse or absent eyebrows (9% vs. 90%, P<0·001) or keratosis pilaris (33% vs. 80%, P=0·001). This study also identified that loose, redundant skin on the hands and feet, 'stippled' dermatoglyphs (pachydermatoglyphia) on the fingertips (eight of 26, 31%) and acanthosis nigricans (17 of 46, 37%) are frequent features of CS.While there is significant phenotypic overlap among syndromes of the Ras/MAPK pathway, individuals with CS are more likely than individuals with CFC syndrome to present with cutaneous papillomas, palmoplantar keratoderma and full eyebrows, and are less likely to present with ulerythema ophryogenes, keratosis pilaris or multiple naevi. The dermatological features of CS, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signalling in cutaneous paraneoplastic syndromes.
Variability in Antibiotic Use Across Nursing Homes and the Risk of Antibiotic-Related Adverse Outcomes for Individual Residents
Authors: Nick Daneman, Susan E. Bronskill, Andrea Gruneir, Alice M. Newman, Hadas D. Fischer, Paula A. Rochon, Geoffrey M. Anderson, Chaim M. Bell
Journal: JAMA Internal Medicine (2015)

Antibiotics are frequently and often inappropriately prescribed to patients in nursing homes. These antibiotics pose direct risks to recipients and indirect risks to others residing in the home.To examine whether living in a nursing home with high antibiotic use is associated with an increased risk of antibiotic-related adverse outcomes for individual residents.In this longitudinal open-cohort study performed from January 1, 2010, through December 31, 2011, we studied 110,656 older adults residing in 607 nursing homes in Ontario, Canada.Nursing home-level antibiotic use was defined as use-days per 1000 resident-days, and facilities were classified as high, medium, and low use according to tertile of use. Multivariable logistic regression modeling was performed to assess the effect of nursing home-level antibiotic use on the individual risk of antibiotic-related adverse outcomes.Antibiotic-related harms included Clostridium difficile, diarrhea or gastroenteritis, antibiotic-resistant organisms (which can directly affect recipients and indirectly affect nonrecipients), allergic reactions, and general medication adverse events (which can affect only recipients).Antibiotics were provided on 2,783,000 of 50,953,000 resident-days in nursing homes (55 antibiotic-days per 1000 resident-days). Antibiotic use was highly variable across homes, ranging from 20.4 to 192.9 antibiotic-days per 1000 resident-days. Antibiotic-related adverse events were more common (13.3%) in residents of high-use homes than among residents of medium-use (12.4%) or low-use homes (11.4%) (P < .001); this trend persisted even among the residents who did not receive antibiotic treatments. The primary analysis indicated that residence in a high-use nursing home was associated with an increased risk of a resident experiencing an antibiotic-related adverse event (adjusted odds ratio, 1.24; 95% CI, 1.07-1.42; P = .003). A sensitivity analysis examining nursing home-level antibiotic use as a continuous variable confirmed an increased risk of resident-level antibiotic-related harms (adjusted odds ratio, 1.004 per additional day of nursing home antibiotic use; 95% CI, 1.001-1.006; P = .01).Antibiotic use is highly variable across nursing homes; residents of high-use homes are exposed to an increased risk of antibiotic-related harms even if they have not directly received these agents. Antibiotic stewardship is needed to improve the safety of all nursing home residents.