tbuckley/cabot-search huggingface dataset:
Continuous Tracheal Gas Insufflation in Preterm Infants with Hyaline Membrane Disease
Authors: GILLES DASSIEU, LAURENT BROCHARD, MOHAMED BENANI, SANDRINE AVENEL, CLAUDE DANAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In mechanically ventilated neonates, the instrumental dead space is a major determinant of total minute ventilation. By flushing this dead space, continuous tracheal gas insufflation (CTGI) may allow reduction of the risk of overinflation. We conducted a randomized trial to evaluate the efficacy of CTGI in reducing airway pressure over the entire period of mechanical ventilation while maintaining oxygenation. A total of 34 preterm newborns, ventilated in conventional pressure-limited mode, were enrolled in two study arms, to receive or not receive CTGI. Transcutaneous Pa(CO(2)) (tcPa(CO(2))) was maintained at 40 to 46 mm Hg in both groups to ensure comparable alveolar ventilation. Respiratory data were collected several times during the first day and daily until Day 28. Both groups were similar at the time of inclusion. During the first 4 d of the study, the difference between peak pressure and positive end-expiratory pressure was significantly lower in the CTGI group by 18% to 35%, with the same tcPa(CO(2)) level and with no difference in the ratio of tcPa(O(2)) to fraction of inspired oxygen (245 +/- 29 versus 261 +/- 46 mm Hg [mean +/- SD] over the first 4 d). Extubation occurred sooner in the CTGI group (p < 0.05), and the duration of mechanical ventilation was shorter (median: 3.6 d; 25th to 75th quartiles: 1.5 to 12.0 d; versus median: 15.6 d; 25th to 75th quartiles: 7.9 to 22.2; p < 0.05) than in the non-CTGI group. CTGI allows the use of low-volume ventilation over a prolonged period and reduces the duration of mechanical ventilation.
Prognostic Value of Nocturnal Cheyne-Stokes Respiration in Chronic Heart Failure
Authors: Paola A. Lanfranchi, Alberto Braghiroli, Enzo Bosimini, Giorgio Mazzuero, Roberto Colombo, Claudio F. Donner, Pantaleo Giannuzzi
Journal: Circulation (1999)

Background —Nocturnal Cheyne-Stokes respiration (CSR) occurs frequently in patients with chronic heart failure (CHF), and it may be associated with sympathetic activation. The aim of the present study was to evaluate whether CSR could affect prognosis in patients with CHF. Methods and Results —Sixty-two CHF patients with left ventricular ejection fraction ≤35%, in NYHA class II to III, underwent clinical evaluation, Doppler echocardiography, ergospirometry, phenylephrine test, Holter recording, and a sleep study to evaluate the occurrence of CSR, expressed as percentage of periodic breathing, and apnea/hypopnea index (AHI) (ie, the number of apneas and hypopneas per hour of recording). During a mean follow-up of 28±13 months, 15 patients died of cardiac causes. Nonsurvivors were in a higher NYHA functional class than survivors ( P &lt;0.001) and had a more depressed left ventricular ejection fraction ( P &lt;0.03), a shorter deceleration time of early filling ( P &lt;0.05), larger left and right atria ( P &lt;0.05 and P &lt;0.02, respectively) and a lower peak V̇ o 2 ( P &lt;0.05). Nonsurvivors also spent a greater percentage of the night in periodic breathing ( P &lt;0.01) with a greater AHI ( P &lt;0.03) and showed lower values of diurnal baroreflex sensitivity ( P &lt;0.05) and of heart rate variability (sdNN: P &lt;0.01). Multivariate analysis revealed the AHI (χ 2 , 10.4; P &lt;0.01), followed by left atrial area (χ 2 , 5.7; P &lt;0.01), as the only independent and additional predictors of subsequent cardiac death. Patients at very high risk for fatal outcome could be identified by an AHI ≥30/h and left atria ≥25 cm 2 . Conclusions —The AHI is a powerful independent predictor of poor prognosis in clinically stable patients with CHF. The presence of an AHI ≥30/h adds prognostic information compared with other clinical, echocardiographic, and autonomic data and identifies patients at very high risk for subsequent cardiac death.
Remission of Nephrotic-Range Albuminuria in Type 1 Diabetic Patients
Authors: Peter Hovind, Peter Rossing, Lise Tarnow, Henrik Toft, Jeppe Parving, Hans-Henrik Parving
Journal: Diabetes Care (2001)

OBJECTIVE—To evaluate the cumulative incidence of nephrotic-range albuminuria (NRA), the frequency of remission, and the impact on progression, we analyzed data from a prospective cohort study of type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS—All of the albuminuric type 1 diabetic patients (n = 321, 121 women), who had at least yearly measurements of glomerular filtration rate (GFR) with a 51Cr-EDTA plasma clearance technique and were followed for at least 3 years, were evaluated. NRA, defined as persistent albuminuria &amp;gt;2,500 mg/24 h, occurred in 126 patients (35 women) aged (mean ± SD) 34 ± 8 years, with duration of diabetes 22 ± 8 years and follow-up time from onset of NRA (median [range]) 8.7 (3.0–20.9) years. Remission of NRA was defined as sustained albuminuria &amp;lt;600 mg/24 h for at least 1 year. RESULTS—The cumulative incidence of NRA was 39%. Remission was induced in 28 of 126 (22%) patients; 21 were predominantly treated with ACE inhibitors, 7 with non–ACE inhibitor medications. Remission lasted 3.6 (1.0–18.1) years. More women (37%) than men (16%) obtained remission (P = 0.01). In the remission group compared with the no-remission group, mean arterial blood pressure (mean ± SEM) was reduced (102 ± 1 vs. 106 ± 1 mmHg, P &amp;lt; 0.01), the rate of decline in GFR was diminished (3.8 ± 0.6 vs. 7.5 ± 0.5 ml · min–1 · year–1, P &amp;lt; 0.001), and serum cholesterol was lower (5.3 ± 0.2 vs. 6.1 ± 0.1 mmol/l, P &amp;lt; 0.01) during the whole follow-up period. No difference in glycemic control was found between groups (HbA1c 9.2 vs. 9.4%, NS). CONCLUSIONS—In contrast to observations made before the use of antihypertensive treatment, our prospective observational study suggests that aggressive antihypertensive treatment with and without ACE inhibitors can induce long-lasting remission in a sizeable fraction of type 1 diabetic patients with NRA. The group of patients obtaining remission is characterized by slow progression of diabetic nephropathy and improved cardiovascular risk profile.
Radial probe EBUS<i>versus</i>CT-guided needle biopsy for evaluation of peripheral pulmonary lesions: an economic analysis
Authors: Daniel P. Steinfort, Danny Liew, Louis B. Irving
Journal: European Respiratory Journal (2012)

Selection of the optimal procedure for minimally invasive diagnosis of peripheral pulmonary lesions (PPLs) may be based on clinical factors; however, selection of diagnostic strategy may also be influenced by cost. Economic analysis of minimally invasive diagnosis of PPL has not been performed previously. Decision-tree analysis was applied to compare downstream costs of endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) with computed tomography-guided percutaneous needle biopsy (CT-PNB). Calculations were based on real costs derived from patient data. Sensitivity analyses and probabilistic sensitivity analysis were undertaken to identify the more cost-beneficial approach for varying input parameter values. Cost-effectiveness calculations were based on estimated disutility, according to the wait-trade-off technique. For base-case analysis, initial evaluation with CT-PNB was cost-beneficial (AU$2,724 versus EBUS-TBLB AU$2,748). The variable which exerted the most influence on cost-benefit outcomes was the cost of managing complications. CT-PNB remained the more cost-effective procedure at base-case parameters, although thresholds were identified during sensitivity analysis where EBUS-TBLB became more cost-effective. The costs of EBUS-TBLB and CT-PNB to evaluate PPL appear to be equivalent, but specific clinical-radiologic factors known to influence procedural outcomes will influence cost-benefit outcomes. Further evaluation of patient preferences and their influence on cost-effectiveness are required.
Two Nuclear Life Cycle-Regulated Genes Encode Interchangeable Subunits c of Mitochondrial ATP Synthase in Podospora anserina
Authors: M. Dequard-Chablat, C. H. Sellem, P. Golik, F. Bidard, A. Martos, M. Bietenhader, J.-P. di Rago, A. Sainsard-Chanet, S. Hermann-Le Denmat, V. Contamine
Journal: Molecular Biology and Evolution (2011)

An F1FO ATP synthase in the inner mitochondrial membrane catalyzes the late steps of ATP production via the process of oxidative phosphorylation. A small protein subunit (subunit c or ATP9) of this enzyme shows a substantial genetic diversity, and its gene can be found in both the mitochondrion and/or nucleus. In a representative set of 26 species of fungi for which the genomes have been entirely sequenced, we found five Atp9 gene repartitions. The phylogenetic distribution of nuclear and mitochondrial Atp9 genes suggests that their evolution has included two independent transfers to the nucleus followed by several independent episodes of the loss of the mitochondrial and/or nuclear gene. Interestingly, we found that in Podospora anserina, subunit c is exclusively produced from two nuclear genes (PaAtp9-5 and PaAtp9-7), which display different expression profiles through the life cycle of the fungus. The PaAtp9-5 gene is specifically and strongly expressed in germinating ascospores, whereas PaAtp9-7 is mostly transcribed during sexual reproduction. Consistent with these observations, deletion of PaAtp9-5 is lethal, whereas PaAtp9-7 deletion strongly impairs ascospore production. The P. anserina PaAtp9-5 and PaAtp9-7 genes are therefore nonredundant. By swapping the 5' and 3' flanking regions between genes we demonstrated, however, that the PaAtp9 coding sequences are functionally interchangeable. These findings show that after transfer to the nucleus, the subunit c gene in Podospora became a key target for the modulation of cellular energy metabolism according to the requirements of the life cycle.
ATM gene inactivation in mantle cell lymphoma mainly occurs by truncating mutations and missense mutations involving the phosphatidylinositol-3 kinase domain and is associated with increasing numbers of chromosomal imbalances
Authors: Emma Camacho, Luis Hernández, Silvia Hernández, Frederic Tort, Beatriz Bellosillo, Silvia Beà, Francesc Bosch, Emili Montserrat, Antonio Cardesa, Pedro L. Fernández, Elias Campo
Journal: Blood (2002)
Guidelines for enteral feeding in adult hospital patients
Authors: M Stroud
Journal: Gut (2003)

Patients with undernutrition to a degree that may impair immunity, wound healing, muscle strength, and psychological drive are common in UK hospital populations.1 These individuals cope poorly with modern medical and surgical interventions and, on average, stay in hospital for approximately five days longer than the normally nourished, incurring approximately 50% greater costs.2,3 Hospitals should therefore aim to provide at least adequate nutrition to all patients. In the majority, this can be achieved by the catering services if they offer good food and care is taken to avoid missed meals and to provide physical help with eating, as necessary. However, even if these ideals are met, many hospital patients do not or cannot eat adequately. Some of these will benefit from oral supplements but others will need active nutritional support. This can usually be provided by enteral tube feeding (ETF). This document contains guidelines covering the indications, benefits, administration, and problems of ETF in adult hospital practice. The guidelines were commissioned by the British Society of Gastroenterology (BSG) as part of an initiative in several areas of clinical practice. They are not rigid protocols and should be used alongside clinical judgement, taking local service provision into account. These guidelines were compiled from the relevant literature by the authors in discussion with dietitians and specialist nutrition nurses. They were subsequently reviewed by the BSG small bowel/nutrition committee and dietetic, nursing, pharmacy, and medical representatives of the British Association of Parenteral and Enteral Nutrition (BAPEN). The strength of evidence used is as recommended by the North of England evidence based guidelines development project.4
Differential Evolution of Cognitive Impairment in Nondemented Older Persons: Results From the Kungsholmen Project
Authors: Katie Palmer, Hui-Xin Wang, Lars Bäckman, Bengt Winblad, Laura Fratiglioni
Journal: American Journal of Psychiatry (2002)

This study was a prospective, population-based examination of the evolution of cognitive impairment, no dementia (CIND).Subjects 75 years old or older living in Stockholm were assessed at baseline and 3 and 6 years later. The severity of CIND was based on age- and education-specific norms on the Mini-Mental State Examination and was classified as mild (N=212), moderate (N=96), or severe (N=57). Mortality, progression to dementia (DSM-III-R), cognitive stability, and cognitive improvement were studied as main outcomes.Of the individuals with mild CIND, 63 (34%) died, 65 (35%) progressed to dementia, 21 (11%) remained stable, and 46 (25%) improved between baseline and first follow-up. The relative risks of progressing to dementia by first follow-up in the subjects with mild, moderate, and severe CIND were 3.6, 5.4, and 7.0, respectively. The relative risk of death decreased with increasing severity of impairment. Individuals who improved at first follow-up did not have a significantly higher risk of later progressing to dementia than subjects who had never been impaired (relative risk=1.4). The absence of a subjective memory complaint predicted improvement (odds ratio=5.4).CIND is a heterogeneous condition: similar proportions of subjects progress to dementia, death, and cognitive improvement over 3 years. There is no increased future risk of progressing to dementia in CIND subjects who improve during that period.
Psychiatrist-patient sexual contact: results of a national survey. I: Prevalence
Authors: Nanette Gartrell, Judith Herman, Silvia Olarte, Michael Feldstein, Russell Localio
Journal: American Journal of Psychiatry (1986)

In a nationwide survey of U.S. psychiatrists, 7.1% (N = 1,057) of the male and 3.1% (N = 257) of the female respondents acknowledged sexual contact with their own patients. Eighty-eight percent of the sexual contacts occurred between male psychiatrists and female patients. All offenders who had been involved with more than one patient were male. Forty-one percent of the offending psychiatrists sought consultation because of their sexual involvement with patients. The authors compare these results with those of previous surveys of psychiatrists and psychologists and discuss the need for addressing this problem within the psychiatric profession.
Inhibition of insulin-like growth factor signaling in ovarian carcinoma cells significantly potentiates paclitaxel cytotoxicity
Authors: Gloria Huang, Marissa Ramirez, Gary Goldberg, Susan Horwitz
Journal: Cancer Research (2007)

4748   Objective: To evaluate the ability of a small molecule inhibitor of the insulin-like growth factor receptor 1 (IGF1R) tyrosine kinase, NVP-AEW541, to block insulin-like growth factor signaling in ovarian cancer cells and to enhance Taxol cytotoxicity.  Methods: Immunoprecipitation and western blot analyses were used to evaluate the ability of NVP-AEW541 to inhibit IGF1R autophosphorylation and downstream signaling in ovarian carcinoma cells (A2780, OVCAR8, HEY). To evaluate the interaction of NVP-AEW541 and Taxol, cells were treated with NVP-AEW541, Taxol, and combinations of both drugs. Taxol and NVP-AEW541 were combined in a variety of ways, utilizing fixed and non-fixed molar ratios; cytotoxicity experiments were performed in complete growth medium containing 10% serum. The fraction of viable cells, compared with untreated cells, was determined by protein staining using the sulforhodamine B (SRB) assay and by colorimetric measurement of cellular reductive capacity (Promega MTS Assay). Calcusyn software was used to generate dose-response curves and calculate the IC50 (dose which results in 50% inhibition of proliferation). The combination index (CI) method of Chou and Talalay was used for the determination of synergy, wherein CI values less than 1 indicate synergy.  Results: Western blot analyses demonstrate that NVP-AEW541 suppresses IGF1R autophosphorylation and downstream AKT phosphorylation resulting from IGF1 or IGF2 stimulation in ovarian carcinoma cells. The presence of NVP-AEW541 significantly potentiates suppression of proliferation by Taxol. In A2780 cells, 1 μM NVP-AEW541 is sufficient to decrease the Taxol IC50 to 0.48 ±0.06 nM, which is significantly lower than the IC50 of Taxol alone, 1.5 ±0.07 nM (p  Conclusions: NVP-AEW541 effectively blocks IGF signaling in ovarian cancer cells. Blockade of IGF signaling with NVP-AEW541 synergistically potentiates Taxol cytotoxicity in ovarian carcinoma cells.
Shortening the Timeline of Pediatric Phase I Trials: The Rolling Six Design
Authors: Jeffrey M. Skolnik, Jeffrey S. Barrett, Bhuvana Jayaraman, Dimple Patel, Peter C. Adamson
Journal: Journal of Clinical Oncology (2008)

To shorten the study conduct timeline of pediatric phase I oncology trials by employing a novel trial design.A comparison of the traditional 3 + 3 patients per cohort, phase I trial design with a novel, rolling six design was performed by using discrete event simulation. The rolling six design allows for accrual of two to six patients concurrently onto a dose level based on the number of patients currently enrolled and evaluable, the number experiencing dose-limiting toxicity (DLT), and the number still at risk of developing a DLT. Clinical trial simulations (n = 1,000) were based on historical data and were performed using SAS 9.1.3 (SAS Institute, Cary, NC). Study timelines and patient numbers were determined for each design, and safety was assessed as a function of the number of DLTs observed.In twelve completed historical studies, the median time to study completion was 452 days (range, 220 to 606 days); number of evaluable participants enrolled was 22 (range, 11 to 33), and DLTs occurring per study was three (range, 0 to 5). In 1,000 study simulations, in which the average time to new patient accrual was 10 days, the average +/- standard deviation (SD) time to study completion was 294 +/- 75 days for the rolling six design versus 350 +/- 84 days for the 3 + 3 design, whereas the number of DLTs per study was the same (average +/- SD, 3.3 +/- 1.1 v 3.2 +/- 1.1 for the rolling six and 3 + 3 designs, respectively).The rolling six design may significantly decrease the duration of pediatric phase I studies without increasing the risk of toxicity. The design will be tested prospectively in upcoming Children's Oncology Group phase I trials.
Association of mitogen-activated protein kinases with microtubules in mouse macrophages.
Authors: A Ding, B Chen, M Fuortes, E Blum
Journal: The Journal of Experimental Medicine (1996)

Taxol, a microtubule-binding diterpene, mimics many effects of lipopolysaccharide (LPS) on mouse macrophages. The LPS-mimetic effects of taxol appear to be under the same genetic control as responses to LPS itself. Thus we have postulated a role for microtubule-associated proteins (MAP) in the response of macrophages to LPS. Stimulation of macrophages by LPS quickly induces the activation of mitogen-activated protein kinases (MAPK). MAPK are generally considered cytosolic enzymes. Herein we report that much of the LPS-activatable pool of MAPK in primary mouse peritoneal macrophages is microtubule associated. By immunofluorescence, MAPK were localized to colchicine- and nocodazole-disruptible filaments. From both mouse brain and RAW 264.7 macrophages, MAPK could be coisolated with polymerized tubulin. Fractionation of primary macrophages into cytosol-, microfilament-, microtubule-, and intermediated filament-rich extracts revealed that approximately 10% of MAPK but none of MAPK kinase (MEK1A and MEK2) was microtubule bound. Exposure of macrophages to LPS did not change the proportion of MAPK bound to microtubules, but preferentially activated the microtubule-associated pool. These findings confirm the prediction that LPS activates a kinase bound to microtubules. Together with LPS-mimetic actions of taxol and the shared genetic control of responses to LPS and taxol, these results support the hypothesis that a major LPS-signaling pathway in mouse macrophages may involve activation of one or more microtubule-associated kinases.
Five-Year Outcomes After Coronary Stenting Versus Bypass Surgery for the Treatment of Multivessel Disease
Authors: Patrick W. Serruys, Andrew T.L. Ong, Lex A. van Herwerden, J. Eduardo Sousa, Adib Jatene, Johannes J.R.M. Bonnier, Jacques P.M.A. Schönberger, Nigel Buller, Robert Bonser, Clemens Disco, Bianca Backx, Paul G. Hugenholtz, Brian G. Firth, Felix Unger
Journal: Journal of the American College of Cardiology (2005)
Thyrotropin-releasing hormone given intrathecally to the rat increases arterial pressure and heart rate.
Authors: K Yashpal, S Gauthier, J L Henry
Journal: Circulation Research (1989)

In view of evidence implicating thyrotropin-releasing hormone (TRH) as a chemical mediator of synaptic transmission onto spinal sympathetic neurons, this peptide was administered intrathecally, in a dose of 6.5 nmol, at the T9 and T2 spinal levels in the anesthetized rat. At the lower thoracic level TRH increased arterial pressure and heart rate; these effects peaked at 4-7 minutes and decayed over the next 15-20 minutes. At the upper thoracic level the pressor and cardioacceleratory responses were roughly similar in time course but were smaller in magnitude. Hexamethonium (10 mg/kg i.v.) was tested on the responses from the lower thoracic level; both pressor and cardioacceleratory responses persisted after hexamethonium pretreatment. In addition, intravenous administration of 6.5 nmol of TRH failed to alter arterial pressure or heart rate, suggesting that the effects produced by the intrathecal administration of TRH were due to an action of the peptide in the spinal cord. The results also indicate that the pressor effect and the increase in heart rate may be mediated in the sympathetic ganglia at least partly via nonnicotinic transmission. Our results provide physiological support for the possibility that TRH is a chemical mediator of synaptic transmission onto sympathetic preganglionic neurons. This study indicates that the functional sympathetic pathways utilizing TRH as a chemical mediator include those regulating arterial pressure and heart rate.