tbuckley/cabot-search huggingface dataset:
Physical and Chemical Strategies for Therapeutic Delivery by Using Polymeric Nanoparticles
Authors: José M. Morachis, Enas A. Mahmoud, Adah Almutairi
Journal: Pharmacological Reviews (2012)

A significant challenge that most therapeutic agents face is their inability to be delivered effectively. Nanotechnology offers a solution to allow for safe, high-dose, specific delivery of pharmaceuticals to the target tissue. Nanoparticles composed of biodegradable polymers can be designed and engineered with various layers of complexity to achieve drug targeting that was unimaginable years ago by offering multiple mechanisms to encapsulate and strategically deliver drugs, proteins, nucleic acids, or vaccines while improving their therapeutic index. Targeting of nanoparticles to diseased tissue and cells assumes two strategies: physical and chemical targeting. Physical targeting is a strategy enabled by nanoparticle fabrication techniques. It includes using size, shape, charge, and stiffness among other parameters to influence tissue accumulation, adhesion, and cell uptake. New methods to measure size, shape, and polydispersity will enable this field to grow and more thorough comparisons to be made. Physical targeting can be more economically viable when certain fabrication techniques are used. Chemical targeting can employ molecular recognition units to decorate the surface of particles or molecular units responsive to diseased environments or remote stimuli. In this review, we describe sophisticated nanoparticles designed for tissue-specific chemical targeting that use conjugation chemistry to attach targeting moieties. Furthermore, we describe chemical targeting using stimuli responsive nanoparticles that can respond to changes in pH, heat, and light.
CONCERNING THE RELATION OF THE COAGULATION TIME OF THE BLOOD TO THROMBOSIS IN PHLEBITIS
Authors: Harlow Brooks, B. S. Crowell
Journal: The Journal of Experimental Medicine (1908)

Positive results have been obtained in but a single set of experiments, namely those in which turpentine was employed. In so far as the results of this preliminary study go, one is led to the conclusion that thrombosis is most readily induced when active inflammatory lesions exist in the blood vessels, associated, probably in most instances, with secondary degenerative changes. Purely mechanical lesions are much less apt to be productive of conditions favorable to thrombosis as a sequence of phlebitis. Marked artificial increase or decrease in the coagulation time of the blood by the use of calcium lactate or citric acid, does not render animals abnormally prone to thrombosis incited by changes other than inflammatory. When true phlebitis exists, thrombosis is apt to be more extensive and less readily resolved, when the coagulation point of the blood has been shortened by the use of calcium lactate, and it is less extensive and more quickly absorbed when the coagulation time has been increased by the administration of citric acid. Experiments as yet incomplete appear to suggest that the increasing in rapidity or slowing of the general circulatory stream has but little bearing on the production of thrombosis in phlebitis, much less, indeed, than clinical and anatomical observations have generally led us to think. We have also been led to suspect that the presence or absence of anastomoses of abundant degree is largely concerned as a factor in determining the location and extent of thrombosis in phlebitis.
Relation Between Activated Clotting Time During Angioplasty and Abrupt Closure
Authors: Craig R. Narins, William B. Hillegass, Charlotte L. Nelson, James E. Tcheng, Robert A. Harrington, Harry R. Phillips, Richard S. Stack, Robert M. Califf
Journal: Circulation (1996)

The purpose of this study was to determine whether the degree of heparin anticoagulation during coronary angioplasty, as measured by the activated clotting time, is related to the risk of abrupt vessel closure.Sixty-two cases of in- and out-of-laboratory abrupt closure in patients in whom intraprocedure activated clotting times were measured were identified from a population of 1290 consecutive patients who underwent non-emergency coronary angioplasty. This group was compared with a matched control population of 124 patients who did not experience abrupt closure. Relative to the control population, patients who experienced abrupt closure had significantly lower initial (median, 350 seconds [25th to 75th percentile, 309 to 401 seconds] versus 380 seconds [335 to 423 seconds], P = .004) and minimum (345 seconds [287 to 387 seconds] versus 370 seconds [321 to 417 seconds], P = .014) activated clotting times. Higher activated clotting times were not associated with an increased likelihood of major bleeding complications. Within this population, a strong inverse linear relation existed between the activated clotting time and the probability of abrupt closure.This study demonstrates a significant inverse relation between the degree of anticoagulation during angioplasty and the risk of abrupt closure. A minimum target activated clotting time could not be identified; rather, the higher the intensity of anticoagulation, the lower the risk of abrupt closure.
In search of childhood asthma: questionnaire, tests of bronchial hyperresponsiveness, and clinical evaluation
Authors: S T Remes
Journal: Thorax (2002)

Background: The definition or diagnosis of asthma is a challenge for both clinicians and epidemiologists. Symptom history is usually supplemented with tests of bronchial hyperresponsiveness (BHR) in spite of their uncertainty in improving diagnostic accuracy. Methods: To assess the interrelationship between respiratory symptoms, BHR, and clinical diagnosis of asthma, the respiratory symptoms of 1633 schoolchildren were screened using a questionnaire (response rate 81.2%) and a clinical study was conducted in a subsample of 247 children. Data from a free running test and a methacholine inhalation challenge test were available in 218 children. The diagnosis of asthma was confirmed by a paediatric allergist. Results: Despite their high specificity (&gt;0.97), BHR tests did not significantly improve the diagnostic accuracy after the symptom history: area under the receiver operator characteristic (ROC) curve was 0.90 for a logistic regression model with four symptoms and 0.94 for the symptoms with free running test and methacholine inhalation challenge results. On the other hand, BHR tests had low sensitivity (0.35–0.47), whereas several symptoms had both high specificity (&gt;0.97) and sensitivity (&gt;0.7) in relation to clinical asthma, which makes them a better tool for asthma epidemiology than BHR. Conclusions: Symptom history still forms the basis for defining asthma in both clinical and epidemiological settings. BHR tests only marginally increased the diagnostic accuracy after symptom history had been taken into account. The diagnosis of childhood asthma should not therefore be overlooked in symptomatic cases with no objective evidence of BHR. Moreover, BHR should not be required for defining asthma in epidemiological studies.
MANAGED CARE DATA AND PUBLIC HEALTH: The Experience of Group Health Cooperative of Puget Sound
Authors: Paul A. Fishman, Edward H. Wagner
Journal: Annual Review of Public Health (1998)

▪ Abstract Traditional group and staff model HMOs have contributed to public health investigations for decades. HMOs offer several advantages for this type of research because of their defined population and provider groups and the integrated nature of care delivery in these organizations. Traditional HMOs have also made investments in sophisticated data systems to support evidence-based care that is supported by high-quality clinical data available in automated information systems. This paper reviews why traditional HMOs are ideal places to conduct public health research and analyzes how recent market trends may threaten this role for managed care.
P29 Securing an intercostal chest drain without sutures
Authors: S. Kesavan, G. D. Angelini
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Securing an intercostal chest drain with sutures after insertion is an important step. Purse string sutures should not be used as it converts a linear incision to a circular, unsightly scar, during the healing process. Two mattress sutures are used—the first suture is to assist the latter closure of the wound after drain removal and the second a stay suture, to secure the drain. In an emergency situation and in the paediatric population, the technique is cumbersome. A novel chest drain is described where the chest drain is secured without sutures. <h3>Method</h3> The novel idea involves securing a chest drain without sutures, with the help of two inflatable balloons (cuffs). An inner (I) and an outer (O) inflatable cuff, with a one way valve to inject air, prevents the chest drain from dislodgement. The risk of infection will be lower as the two inflatable cuffs and the intercostal muscles around the chest drain will provide a perfect fit. The chest drain is removed after deflating the balloons (cuffs) at the end of inspiration. Small gauge chest drains do not require a suture and the linear incision can be closed by suture strips, after removal of the chest drain. The novel chest drain is especially useful in patients with pneumothorax and in the paediatric population, providing a snug, secure and a stable position of the chest drain. <h3>Conclusion</h3> The above chest drain provides a suture less method to secure an intercostal chest drain. It is especially useful in an emergency situation (tension pneumothorax) and in the paediatric population.
Importance of preexcited QRS morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways.
Authors: L Fananapazir, L D German, J J Gallagher, J E Lowe, E N Prystowsky
Journal: Circulation (1990)

The present investigation evaluates the ability of several electrocardiographic (ECG) and electrophysiologic methods to identify multiple accessory pathways in 47 patients in whom the presence and sites of multiple accessory pathways were confirmed intraoperatively. To establish ECG features that suggested the presence of multiple accessory pathways in these patients, we initially studied the 12-lead ECG during maximal preexcitation in 101 patients with single accessory pathways. Distinctive 12-lead ECG patterns were noted for six defined anatomic areas around the right and left atrioventricular groove. Multiple preexcited QRS morphologies, each typical for a separate accessory pathway, and atypical preexcited QRS morphologies were recorded during atrial fibrillation in 31 of 47 (66%) patients with multiple accessory pathways. By comparison, the ECG during sinus rhythm and rapid atrial pacing identified 14 (32%) and 26 (55%) of the patients, respectively. In 12 (26%) patients in whom evidence for multiple accessory pathways was absent from endocardial mapping data, atrial fibrillation provided the diagnosis. In five (11%) patients, atrial fibrillation was the only method that demonstrated the presence of multiple accessory pathways. A combination of ECG findings during atrial fibrillation and rapid atrial pacing plus endocardial mapping data identified 43 (91%) of the patients with multiple accessory pathways. There were two unique fusion patterns on the 12-lead ECG that were characteristic of specific multiple accessory pathway combinations.(ABSTRACT TRUNCATED AT 250 WORDS)
Systolic and Diastolic Heart Failure in the Community
Authors: Francesca Bursi, Susan A. Weston, Margaret M. Redfield, Steven J. Jacobsen, Serguei Pakhomov, Vuyisile T. Nkomo, Ryan A. Meverden, Véronique L. Roger
Journal: JAMA (2006)

The heart failure (HF) syndrome is heterogeneous. While it can be defined by ejection fraction (EF) and diastolic function, data on the characteristics of HF in the community are scarce, as most studies are retrospective, hospital-based, and rely on clinically indicated tests. Further, diastolic function is seldom systematically assessed based on standardized techniques.To prospectively measure EF, diastolic function, and brain natriuretic peptide (BNP) in community residents with HF.Echocardiographic measures of EF and diastolic function, measurement of blood levels of BNP, and 6-month mortality.Olmsted County residents with incident or prevalent HF (inpatients or outpatients) between September 10, 2003, and October 27, 2005, were prospectively recruited to undergo assessment of EF and diastolic function by echocardiography and measurement of BNP.A total of 556 study participants underwent echocardiography at HF diagnosis. Preserved EF (> or =50%) was present in 308 (55%) and was associated with older age, female sex, and no history of myocardial infarction (all P<.001). Isolated diastolic dysfunction (diastolic dysfunction with preserved EF) was present in 242 (44%) patients. For patients with reduced EF, moderate or severe diastolic dysfunction was more common than when EF was preserved (odds ratio, 1.67; 95% confidence interval [CI], 1.11-2.51; P = .01). Both low EF and diastolic dysfunction were independently related to higher levels of BNP. At 6 months, mortality was 16% for both preserved and reduced EF (age- and sex-adjusted hazard ratio, 0.85; 95% CI, 0.61-1.19; P = .33 for preserved vs reduced EF).In the community, more than half of patients with HF have preserved EF, and isolated diastolic dysfunction is present in more than 40% of cases. Ejection fraction and diastolic dysfunction are independently related to higher levels of BNP. Heart failure with preserved EF is associated with a high mortality rate, comparable to that of patients with reduced EF.
Cystic fibrosis papers of the year 2009
Authors: Ian M Balfour-Lynn
Journal: Journal of the Royal Society of Medicine (2010)

The literature search was conducted using PubMed (www.ncbi.nlm.nih.gov/sites/entrez ), entering the search term ‘cystic fibrosis’, for the period 1 November 2008 to 15 October 2009. There were 1525 papers identified, and when limits were set for ‘clinical trial’ and ‘randomized controlled trial’ this left 40 papers. The papers selected for this review are a personal choice of studies with important or interesting clinical messages.
Physiological and biomechanical adaptations to the cycle to run transition in Olympic triathlon: review and practical recommendations for training
Authors: Gregoire P Millet, Veronica E Vleck
Journal: British Journal of Sports Medicine (2000)

Current knowledge of the physiological, biomechanical, and sensory effects of the cycle to run transition in the Olympic triathlon (1.5 km, 10 km, 40 km) is reviewed and implications for the training of junior and elite triathletes are discussed. Triathlon running elicits hyperventilation, increased heart rate, decreased pulmonary compliance, and exercise induced hypoxaemia. This may be due to exercise intensity, ventilatory muscle fatigue, dehydration, muscle fibre damage, a shift in metabolism towards fat oxidation, and depleted glycogen stores after a 40 km cycle. The energy cost (C R ) of running during the cycle to run transition is also increased over that of control running. The increase in C R varies from 1.6% to 11.6% and is a reflection of triathlete ability level. This increase may be partly related to kinematic alterations, but research suggests that most biomechanical parameters are unchanged. A more forward leaning trunk inclination is the most significant observation reported. Running pattern, and thus running economy, could also be influenced by sensorimotor perturbations related to the change in posture. Technical skill in the transition area is obviously very important. The conditions under which the preceding cycling section is performed—that is, steady state or stochastic power output, drafting or non-drafting—are likely to influence the speed of adjustment to transition. The extent to which a decrease in the average 10 km running speed occurs during competition must be investigated further. It is clear that the higher the athlete is placed in the field at the end of the bike section, the greater the importance to their finishing position of both a quick transition area time and optimal adjustment to the physiological demands of the cycle to run transition. The need for, and current methods of, training to prepare junior and elite triathletes for a better transition are critically reviewed in light of the effects of sequential cycle to run exercise.
Cyclooxygenase inhibition abrogates aeroallergen-induced immune tolerance by suppressing prostaglandin I2 receptor signaling
Authors: Weisong Zhou, Kasia Goleniewska, Jian Zhang, Daniel E. Dulek, Shinji Toki, Matthew T. Lotz, Dawn C. Newcomb, Madison G. Boswell, Vasiliy V. Polosukhin, Ginger L. Milne, Pingsheng Wu, Martin L. Moore, Garret A. FitzGerald, R. Stokes Peebles
Journal: Journal of Allergy and Clinical Immunology (2014)
Chemotherapeutic Options in Chronic Lymphocytic Leukemia: a Meta-analysis of the Randomized Trials
Authors: Cll Trialists' CollaborativeGroup
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: The randomized trials that evaluate the timing and intensity of initial chemotherapy for chronic lymphocytic leukemia (CLL) have, in general, been too small to provide separately reliable results. We compared the effects on survival of the following: a) immediate versus deferred chemotherapy for early-stage CLL and b) combination chemotherapy (e.g., cyclophosphamide and vincristine plus prednisone/prednisolone [ COP] or COP plus doxorubicin [CHOP]) versus single-agent chlorambucil as first-line treatment for more advanced disease. METHODS: All relevant randomized trials, whether published or not, were sought for a collaborative meta-analysis involving centralized review of the data for each patient. RESULTS: There were 2048 patients with early disease in six trials of immediate versus deferred chemotherapy (chlorambucil or chlorambucil plus prednisone/prednisolone). The 10-year survival was slightly worse (but not statistically significantly so) with immediate chemotherapy (44% versus 47% survival; difference = −3%; 95% confidence interval [ CI] = −10% to 4%). There were another 2022 patients in 10 trials of combination chemotherapy versus chlorambucil, with or without prednisone/prednisolone. The 5-year survival was 48% in both cases (difference = 0%; 95% CI = −6% to 5%). A subgroup of six of these 10 trials involved an anthracycline-containing regimen but again overall survival appeared no better than with chlorambucil (anthracycline-based regimen: 325 deaths among 627 patients; chlorambucil: 306 deaths among 636 patients; death rate ratio = 1.07; 95% CI = 0.91-1.25; not statistically significant). CONCLUSIONS: In terms of survival, these trials support a conservative treatment strategy for CLL, i.e., no chemotherapy for most patients with early-stage disease, and single-agent chlorambucil as the first line of treatment for most patients with advanced disease, with no evidence of benefit from early inclusion of an anthracycline. This strategy will, however, need to be reconsidered as mature results become available from trials of other agents.
The immediate effects of foot orthoses on functional performance in individuals with patellofemoral pain syndrome
Authors: C J Barton, H B Menz, K M Crossley
Journal: British Journal of Sports Medicine (2010)

Patellofemoral pain syndrome (PFPS) often results in reduced functional performance. There is growing evidence for the use of foot orthoses to treat this multifactorial condition. In this study, the immediate effects of foot orthoses on functional performance and the association of foot posture and footwear with improvements in function were evaluated.Fifty-two individuals with PFPS (18-35 years) were prescribed prefabricated foot orthoses (Vasyli Pro; Vasyli International, Labrador, Australia). Functional outcome measures evaluated included the change in (1) pain and (2) ease of a single-leg squat on a five-point Likert scale, and change in the number of (3) pain-free step downs and (4) single-leg rises from sitting. The association of foot posture using the Foot Posture Index, navicular drop and calcaneal angle relative to subtalar joint neutral; and the footwear motion control properties scale score with improved function were evaluated using Spearman's ρ statistics.Prefabricated foot orthoses produced significant improvements (p<0.05) for all functional outcome measures. A more pronated foot type and poorer footwear motion control properties were found to be associated with reduced pain during the single-leg squat and improvements in the number of pain-free single-leg rises from sitting when wearing foot orthoses. In addition, a more pronated foot type was also found to be associated with improved ease of completing a single-leg squat when wearing foot orthoses.Prefabricated foot orthoses provide immediate improvements in functional performance, and these improvements are associated with a more pronated foot type and poorer footwear motion control properties.
Critical Closing Pressure of Vessels Supplying the Capillary Loops of the Nailfold
Authors: PETER GASKELL, ASHLEY M. KRISMAN
Journal: Circulation Research (1958)

The critical closing pressure (CCP) of vessels supplying the capillary loops of the nailfold was estimated as the digital systolic pressure minus the air pressure required on the finger to just prevent flow of blood in the capillary loops. The digital blood pressure was estimated by an auscultatory method and the presence or absence of flow in the loops was detected by direct microscopic examination. It was shown that the method is valid and does not simply measure a local intravascular pressure or some rheological factor. The CCP was lower after body heating than after body cooling and was markedly reduced by anesthetization of the digital nerves. In hypertensive patients the CCP was higher than in normal subjects.
Visualization of Endogenous p53-Mediated Transcription <i>In vivo</i> Using Sodium Iodide Symporter
Authors: Kwang Il Kim, June-Key Chung, Joo Hyun Kang, Yong Jin Lee, Jae Hoon Shin, Hyun Jeong Oh, Jae Min Jeong, Dong Soo Lee, Myung Chul Lee
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To develop a gamma camera imaging method for the determination of endogenous gene expression, we evaluated the expression of endogenous p53 gene using human sodium iodide symporter (hNIS) gene as reporter. Experimental Design: We constructed cis-p53RE-hNIS reporter vector placed under control of an artificial enhancer (p53RE). Moreover, we transfected it into human hepatoma cell line SK-Hep1 by liposome. Geneticin was used for the selection of stable transfectant (SK-Hep1p53NIS). To evaluate the function of hNIS, the inhibition study was examined with 1 mmol/L potassium perchlorate. After treatment of Adriamycin with serial dose for 24 hours, we measured the uptake of 125I and did Western blot analysis to evaluate expression of p53 protein. Tumor xenografts were produced in nude mice by s.c. injection of SK-Hep1p53NIS cells. After 7 days, scintigraphic images of nude mice before and after Adriamycin treatment were obtained using [99mTc]-pertechnetate. Results: In the SK-Hep1p53NIS cells, Adriamycin-treated cells accumulated up to three times higher than did nontreated cells. Potassium perchlorate inhibited completely the uptake of 125I. As Adriamycin dose increased, radioiodide uptake was significantly correlated with activated p53 as well as total p53 protein level. When Adriamycin (2 mg/kg) was treated in the same mice, a significantly higher uptake of [99mTc]-pertechnetate was observed in SK-Hep1p53NIS xenografts compared with nontreated xenografts (P &amp;lt; 0.05, unpaired t test). Conclusions: These results suggest that p53 expression level can be monitored by NIS gene expression using cis-p53RE-hNIS system in vitro and in vivo.