tbuckley/cabot-search huggingface dataset:
Disturbances of Rhythm in the Cold-Blooded Heart Under Aconitine
Authors: S. M. TENNEY, A. M. WEDD
Journal: Circulation Research (1954)

The cold-blooded auricle under aconitine shows an early profound depression in rhythmicity but recovers in from 5 to 10 minutes to develop a high rate of spontaneous beating which may be considered a tachycardia for this preparation. Although arrhythmias do not appear spontaneously, a single, properly-timed stimulus to the auricle under aconitine initiates a multiple response which appears like ordinary fibrillation or flutter. The alterations in fundamental properties of the auricle which are required to elicit multiple responses favor a re-entrant rather than a focal mechanism of the induced arrhythmia.
Ultrasound Imaging of Apoptosis in Tumor Response: Novel Preclinical Monitoring of Photodynamic Therapy Effects
Authors: Behzad Banihashemi, Roxana Vlad, Branislav Debeljevic, Anoja Giles, Michael C. Kolios, Gregory J. Czarnota
Journal: Cancer Research (2008)

Abstract High-frequency ultrasound is a novel method to detect apoptotic cell death based on changes in cell morphology that cause alterations in the viscoelastic and, consequently, the acoustic properties of cell ensembles and tissues. In this study, we evaluated the first preclinical tumor-based use of high-frequency ultrasound spectroscopy to noninvasively monitor tumor treatment by following xenograft malignant melanoma tumor responses to photodynamic therapy (PDT) in vivo. We observed a time-dependant increase in ultrasound backscatter variables after treatment. The observed increases in spectroscopic variables correlated with morphologic findings, indicating increases in apoptotic cell death, which peaked at 24 hours after PDT. We analyzed the changes in spectral slope and backscatter in relation to apoptosis and histologic variations in cell nuclear size. Changes in spectral slope strongly correlated with the changes in mean nuclear size over time, associated with apoptosis, after PDT (P &amp;lt; 0.05). At 48 hours, a decrease in ultrasound backscatter was observed, which could be explained by an increase in cell nuclear degradation. In summary, we show that high-frequency ultrasound spectroscopic variables can be used noninvasively to monitor response after treatment in a preclinical tumor cancer model. These findings provide a foundation for future investigations regarding the use of ultrasound to monitor and aid the customization of treatments noninvasively based on responses to specific interventions. [Cancer Res 2008;68(20):8590–6]
Effect of Bar-Code Technology on the Safety of Medication Administration
Authors: Eric G. Poon, Carol A. Keohane, Catherine S. Yoon, Matthew Ditmore, Anne Bane, Osnat Levtzion-Korach, Thomas Moniz, Jeffrey M. Rothschild, Allen B. Kachalia, Judy Hayes, William W. Churchill, Stuart Lipsitz, Anthony D. Whittemore, David W. Bates, Tejal K. Gandhi
Journal: New England Journal of Medicine (2010)

Serious medication errors are common in hospitals and often occur during order transcription or administration of medication. To help prevent such errors, technology has been developed to verify medications by incorporating bar-code verification technology within an electronic medication-administration system (bar-code eMAR).We conducted a before-and-after, quasi-experimental study in an academic medical center that was implementing the bar-code eMAR. We assessed rates of errors in order transcription and medication administration on units before and after implementation of the bar-code eMAR. Errors that involved early or late administration of medications were classified as timing errors and all others as nontiming errors. Two clinicians reviewed the errors to determine their potential to harm patients and classified those that could be harmful as potential adverse drug events.We observed 14,041 medication administrations and reviewed 3082 order transcriptions. Observers noted 776 nontiming errors in medication administration on units that did not use the bar-code eMAR (an 11.5% error rate) versus 495 such errors on units that did use it (a 6.8% error rate)--a 41.4% relative reduction in errors (P<0.001). The rate of potential adverse drug events (other than those associated with timing errors) fell from 3.1% without the use of the bar-code eMAR to 1.6% with its use, representing a 50.8% relative reduction (P<0.001). The rate of timing errors in medication administration fell by 27.3% (P<0.001), but the rate of potential adverse drug events associated with timing errors did not change significantly. Transcription errors occurred at a rate of 6.1% on units that did not use the bar-code eMAR but were completely eliminated on units that did use it.Use of the bar-code eMAR substantially reduced the rate of errors in order transcription and in medication administration as well as potential adverse drug events, although it did not eliminate such errors. Our data show that the bar-code eMAR is an important intervention to improve medication safety. (ClinicalTrials.gov number, NCT00243373.)
The p53 Pathway and Outcome among Patients with T1G3 Bladder Tumors
Authors: Elena López-Knowles, Silvia Hernández, Manolis Kogevinas, Josep Lloreta, Alex Amorós, Adonina Tardón, Alfredo Carrato, Sirish Kishore, Consol Serra, Núria Malats, Francisco X. Real
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The aim was to analyze Tp53 and HDM2 in T1G3 bladder tumors and to determine the prognostic value of their alterations. Experimental Design: Tumors (n = 119) were extracted from a prospective study of 1,356 bladder cancers. Tp53 mutations (exons 4-9) were assessed by sequencing of PCR products. HDM2 dose was assessed by quantitative PCR. p53, HDM2, and the products of p53 target genes were analyzed by immunohistochemistry. Cases were distributed in three categories. The association with prognosis was determined using Kaplan-Meier and Cox analyses. Results: Eighty-five percent of tumors harbored alterations in Tp53 or HDM2. In group 1 (n = 77), 69 tumors had inactivating Tp53 mutations (58%), and 8 had HDM2 gains (7%). Group 2 (n = 24) comprised tumors overexpressing p53 in the absence of mutations (20%). Group 3 tumors (n = 18) had no alterations. HDM2 gains were associated to HDM2 overexpression and to wild-type Tp53. Expression of type 1 insulin-like growth factor receptor, 14-3-3 σ, and cyclooxygenase-2 was similar in groups 1 and 2 and significantly different from group 3. Survivin was expressed in the majority of tumors regardless of p53 pathway status. Taking group 3 as reference, the hazard ratios (HR) for recurrence, progression, and death were not significantly different in the other patient groups. HRs for recurrence were 1.13 for group 1 [95% confidence interval (95% CI), 0.25-5.03] and 1.40 for group 2 (95% CI, 0.27-7.20). HRs for progression were 0.50 for group 1 (95% CI, 0.18-1.40) and 0.25 for group 2 (95% CI, 0.05-1.29). Conclusions: The p53 pathway is inactivated in most T1G3 bladder tumors. These genetic alterations do not independently predict patient's prognosis.
Lack of Population Diversity in Commonly Used Human Embryonic Stem-Cell Lines
Authors: Jack T. Mosher, Trevor J. Pemberton, Kristina Harter, Chaolong Wang, Erkan O. Buzbas, Petr Dvorak, Carlos Simón, Sean J. Morrison, Noah A. Rosenberg
Journal: New England Journal of Medicine (2009)

To the Editor: Human embryonic stem-cell research may lead to new methods of drug discovery, insights into mechanisms of disease, and eventually, cellular therapies. The potential benefit to patient populations may depend partially on the diversity of the stem-cell lines that are available for research and clinical use. However, investigators have been unable to target their research to diverse subgroups of existing lines or to ensure the inclusion of lines from the human populations most relevant to their diseases of interest, because almost no information has been available on the human population origin of existing stem-cell lines. Therefore, with the . . .
Analysis of deaths occurring within the Nottingham trial of faecal occult blood screening for colorectal cancer
Authors: D. K. Whynes, C. M. Mangham, T. W. Balfour, J. H. Scholefield
Journal: Gut (2010)

<h3>Objective</h3> To report the causes of, and ages at, death of subjects in an English colorectal cancer screening trial. <h3>Design and setting</h3> Analysis of 78 708 deaths occurring between 1981 and 2008, within the Nottingham randomised controlled trial of biennial faecal occult blood testing. <h3>Main outcome measures</h3> Cause of death, age at death by sex and by cause. <h3>Results</h3> Significantly more subjects died from verified colorectal cancer in the trial9s control group than in the intervention group (3.2% vs 2.9%). For no other major cause of death was the difference in proportion across the two groups statistically significant. Age at death was lower for cancer than for other principal causes, except for ischaemic heart disease among women. However, mean age at death was higher for colorectal cancer than for other cancers, except for prostate cancer among men. Increasing levels of material deprivation significantly lowered the expected ages at death, independently of cause. For both men and women, the mean age at death from all causes for screening participants was higher than that of controls and non-participants. Mean deprivation was lowest among participants. Of those participating in screening, and dying from colorectal cancer, subjects receiving negative test results lived significantly longer than those who received positive test results. However, if dying from other causes, they died at an earlier age. <h3>Conclusions</h3> The age at death from colorectal cancer is higher than that of most other cancers. Those accepting a screening invitation live longer than non-participants. In part, this difference is explained by relative deprivation. Among screening participants, the receipt of a positive, as opposed to a negative, test result is associated with a later age at death.
Management of children with brain tumors in Paraguay
Authors: Jacquelyn L. Baskin, Eva Lezcano, Bo Sung Kim, Diego Figueredo, Alvaro Lassaletta, Antonio Perez-Martinez, Luis Madero, Miguela A. Caniza, Scott C. Howard, Angelica Samudio, Jonathan L. Finlay
Journal: Neuro-Oncology (2012)

Cure rates among children with brain tumors differ between low-income and high-income countries. To evaluate causes of these differences, we analyzed aspects of care provided to pediatric neuro-oncology patients in a low middle-income South American country. Three methods were used to evaluate treatment of children with brain tumors in Paraguay: (1) a quantitative needs assessment questionnaire for local treating physicians, (2) site visits to assess 3 tertiary care centers in Asunción and a satellite clinic in an underdeveloped area, and (3) interviews with health care workers from relevant disciplines to determine their perceptions of available resources. Treatment failure was defined as abandonment of therapy, relapse, or death. All 3 tertiary care facilities have access to chemotherapy and pediatric oncologists but lack training and tools for neuropathology and optimal neurosurgery. The 2 public hospitals also lack access to appropriate radiological tests and timely radiotherapy. These results demonstrate disparities in Paraguay, with rates of treatment failure ranging from 37% to 83% among the 3 facilities. National and center-specific deficiencies in resources to manage pediatric brain tumors contribute to poor outcomes in Paraguay and suggest that both national and center-specific interventions are warranted to improve care. Disparities in Paraguay reflect different levels of governmental and philanthropic support, program development, and socio-economic status of patients and families, which must be considered when developing targeted strategies to improve management. Effective targeted interventions can serve as a model to develop pediatric brain tumor programs in other low- and middle-income countries.
Epigenetic Modifications in Double-Strand Break DNA Damage Signaling and Repair
Authors: Dorine Rossetto, Andrew W. Truman, Stephen J. Kron, Jacques Côté
Journal: Clinical Cancer Research (2010)

Abstract Factors involved in the cellular response to double-strand break (DSB) DNA damage have been identified as potential therapeutic targets that would greatly sensitize cancer cells to radiotherapy and genotoxic chemotherapy. These targets could disable the repair machinery and/or reinstate normal cell-cycle checkpoint leading to growth arrest, senescence, and apoptosis. It is now clear that a major aspect of the DNA damage response occurs through specific interactions with chromatin structure and its modulation. It implicates highly dynamic posttranslational modifications of histones that are critical for DNA damage recognition and/or signaling, repair of the lesion, and release of cell-cycle arrest. Therefore, drugs that target the enzymes responsible for these modifications, or the protein modules reading them, have very high therapeutic potential. This review presents the current state of knowledge on the different chromatin modifications and their roles in each step of eukaryotic DSB DNA damage response. Clin Cancer Res; 16(18); 4543–52. ©2010 AACR.
Dinucleotide relative abundance extremes: a genomic signature
Authors: Samuel Kariin, Chris Burge
Journal: Trends in Genetics (1995)

Early biochemical experiments established that the set of dinucleotide odds ratios or 'general design' is a remarkably stable property of the DNA of an organism, which is essentially the same in protein-coding DNA, bulk genomic DNA, and in different renaturation rale and density gradient fractions of genomic DNA in many organisms. Analysis of currently available genomic sequence data has extended these earlier results, showing that the general designs of disjoint samples of a genome are substantially more similar to each other than to those of sequences from other organisms and that closely related organisms have similar general designs. From this perspective, the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome, which can discriminate between sequences from different organisms. Dinucleotide-odds ratio values appear to reflect not only the chemistry of dinucleotide stacking energies and base-step conformational preferences, but also the species-specific properties of DNA modification, replication and repair mechanisms.
Descriptive epidemiology of CNS tumors in France: results from the Gironde Registry for the period 2000-2007
Authors: I. Baldi, A. Gruber, A. Alioum, E. Berteaud, P. Lebailly, A. Huchet, T. Tourdias, G. Kantor, J. P. Maire, A. Vital, H. Loiseau, K. Champeaux, M. Dhauteribes, S. Eimer, E. Gimbert, D. Liguoro, P. Monteil, G. Penchet, F. San-Galli, J. Vignes
Journal: Neuro-Oncology (2011)

An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry provides here the first data on CNS tumor incidence and trends in France for all histological types, including benign and malignant tumors, for the period 2000–2007. Incidence rates were calculated globally and for each histological subtype. For trends, a piecewise log-linear model was used. The overall annual incidence rate was found to be 17.6/100 000. Of this rate, 7.9/100 000 were neuroepithelial tumors and 6.0/100 000 were meningiomas. An overall increase in CNS tumor incidence was observed from 2000 to 2007, with an annual percent change (APC) of +2.33%, which was explained mainly by an increase in the incidence of meningiomas over the 8-year period (APC = +5.4%), and also more recently by an increase in neuroepithelial tumors (APC = +7.45% from 2003). The overall increase was more pronounced in women and in the elderly, with an APC peaking at +24.65% in subjects 85 and over. The increase in the incidence rates we observed may have several explanations: not only improvements in registration, diagnosis, and clinical practice, but also changes in potential risk factors.
Increased Expression of NAD(P)H Oxidase Subunit p67phox in the Renal Medulla Contributes to Excess Oxidative Stress and Salt-Sensitive Hypertension
Authors: Di Feng, Chun Yang, Aron M. Geurts, Terry Kurth, Mingyu Liang, Jozef Lazar, David L. Mattson, Paul M. O'Connor, Allen W. Cowley
Journal: Cell Metabolism (2012)
Effect of salmeterol on Haemophilus influenzae infection of respiratory mucosa in vitro
Authors: RB Dowling, M Johnson, PJ Cole, R Wilson
Journal: European Respiratory Journal (1998)

Haemophilus influenzae is a common bacterial pathogen causing human respiratory tract infections. We have previously shown that the beta2-agonist salmeterol reduces damage to the respiratory mucosa caused by Pseudomonas aeruginosa in vitro. We have now investigated the effect of salmeterol on H. influenzae infection of adenoid tissue in an organ culture by scanning electron microscopy. Tissue was preincubated with or without salmeterol (4x10(-7)M), prior to infection with H. influenzae and incubated for 12 or 24 h. Infected organ cultures had increased epithelial damage and decreased numbers of both ciliated and unciliated cells at 12h, which were significantly different (p < or = 0.01) from the controls at 24 h. Salmeterol (4x10(-7)M) significantly (p < or = 0.03) reduced damage and loss of ciliated cells in infected organ cultures at both 12 and 24, and significantly (p < or = 0.03) reduced loss of unciliated cells at 24 h. Salmeterol had no effect on the density of bacteria adhering to each individual mucosal feature or the total number of bacteria adhering to the organ culture. These results suggest that salmeterol protects the respiratory epithelium against Haemophilus influenzae-induced damage. The mechanism of salmeterol cytoprotection and its potential clinical relevance remain to be investigated.
Ursodeoxycholic Acid: A Safe and Effective Agent for Dissolving Cholesterol Gallstones
Authors: G. STEPHEN TINT
Journal: Annals of Internal Medicine (1982)

Ursodeoxycholic acid, 250 to 300, 500 to 600, or 900 to 1000 mg/d, was given orally for 6 to 38 months to 53 patients with cholesterol gallstones and functioning gallbladders. Forty-two patients had greater than 50% reduction in gallstone volume, number, or both, without apparent dose dependence and 27 of these patients had complete gallstone dissolution. Results of laboratory studies including liver function tests were not affected adversely and biliary lithocholic acid concentration did not increase during therapy. Most biliary symptoms seemed to disappear within 3 months and no patient developed diarrhea. Large diameter and increased number of gallstones were found to hinder dissolution. The percentage of biliary ursodeoxycholic acid increased with increasing dose and reached a maximum of 50% to 60% of total bile acids at a dose of about 10 to 12 mg/kg body weight d. Biliary lithogenic index was reduced significantly during treatment with ursodeoxycholic acid, 500 to 600 and 900 to 1000 mg/d. Thus, ursodeoxycholic acid appears to be a safe and effective alternative to surgery in selected patients with gallstones.
Anti-citrullinated protein antibodies have a low avidity compared with antibodies against recall antigens
Authors: P. Suwannalai, H. U. Scherer, D. van der Woude, A. Ioan-Facsinay, C. M. Jol-van der Zijde, M. J. D. van Tol, J. W. Drijfhout, T. W. J. Huizinga, R. E. M. Toes, L. A. Trouw
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. Recent ongoing evidence indicates that the ACPA response broadens before precipitation of full-blown RA, as indicated by a more extensive isotype usage and an increased citrullinated epitope recognition profile. Nonetheless, the evolution of the ACPA response is still poorly understood and might intrinsically differ from the protective responses against pathogens. <h3>Methods</h3> The avidity and the avidity maturation of ACPA in relation to the avidity of antibodies against recall antigens were analysed. <h3>Results</h3> The avidity of ACPA was significantly lower than the avidity of antibodies to the recall antigens tetanus toxoid and diptheria toxoid. Moreover, ACPA did not show avidity maturation during longitudinal follow-up and ACPA avidity was also relatively low in patients who displayed extensive isotype switching. <h3>Conclusions</h3> These observations indicate that the natural evolution of ACPA differs from the development of antibodies against recall antigens. These data also indicate that ACPA avidity maturation and isotype switching are disconnected, whereby extensive isotype switching occurs in the setting of restricted avidity maturation. Intrinsic differences between the RA-specific autoantibody system and protective antibody responses against pathogens could be of relevance for designing novel B cell-targeted therapies for RA.
Review of decannulation experience and duration of tracheostomy within the Newcastle upon Tyne Hospitals NHS Foundation Trust
Authors: Josephine Nicholas, Christopher O'Brien
Journal: European Respiratory Journal (2011)

Background:  Tracheostomy is increasingly used to manage airway difficulties in paediatric respiratory management. It is important that parents are informed of the likely duration of tracheostomy in different conditions and the prognosis for decannulation.   Aims:  The aim of this project was to review the experience of paediatric tracheostomy decannulation in the Newcastle upon Tyne Hospital NHS Foundation (NUTH) Trust over the last 6 years.   Methods:  This retrospective review looked at all decannulation episodes in children within the NUTH Trust from January 2005 to December 2010. The notes of the patients identified were reviewed to collect data.   Results:  56 patient episodes were identified, of those, 48 patients were included. The median duration of tracheostomy was 14 months and the median age at decannulation was 26 months. The indications for tracheostomy were: subglottic stenosis (31%), airway malacia (21%), airway mass (13%), airway obstruction (10%) and other (25%). The median duration for these indications were 35, 17.5, 8, 12 and 11.5 months respectively. 81.25% (39) of planned decannulations were successful. Surprisingly 61.54% (24) of successful decannulations had trachy-cutaneous fistulas requiring surgical closure. It appeared that fistulas were associated with patients who were of a younger age at tracheostomy (4.5 vs. 8 months) or who have had a longer duration of tracheostomy (20 vs. 12 months).   Conclusions:  This review has highlighted likely duration of tracheostomy for the common conditions and prognosis for decannulation. It has also revealed a surprisingly high rate of trachy-cutaneous fistula.