tbuckley/cabot-search huggingface dataset:
The pulmonary protein C system: preventive or therapeutic target in acute lung injury?
Authors: M. J Schultz, B. Dixon, M. Levi
Journal: Thorax (2009)

Acute lung injury or its more severe form—acute respiratory distress syndrome (ARDS)—are common and important intensive care syndromes affecting many patients. Acute lung injury is characterised by damage to the alveolar-capillary membrane resulting in alveolar flooding, pulmonary inflammation and alveolar coagulopathy, and changes in surfactant properties with severe impairment of oxygenation and respiratory failure mandating mechanical ventilation. It is rarely present at the time of hospital admission but develops over a period of hours to days in subsets of patients with predisposing conditions such as trauma, shock or sepsis, and accompanying interventions including mechanical ventilation and transfusion.1 Acute lung injury may therefore be viewed as a potentially preventable complication. Indeed, implementation of acute lung injury prevention strategies such as lung-protective mechanical ventilation using normal-sized tidal volumes and restrictive blood transfusion leads to a significant decrease in acute lung injury and mortality of mechanically ventilated patients.2 Pharmacotherapies targeting progression to acute lung injury may also benefit patients at risk of this complication. One such preventive strategy might be attenuation of pulmonary coagulopathy.

Recent studies have shown that prominent changes in alveolar fibrin turnover are intrinsic to acute lung injury.3 The profile and extent of these changes vary with the severity of the injury.4 The mechanisms that contribute to pulmonary coagulopathy in acute lung injury are supposed to be similar to those found in the intravascular spaces in severe systemic inflammation (eg, sepsis or septic shock).5–7 Indeed, in acute lung injury, alveolar thrombin generation seems to be mediated, at least in part, by the tissue factor (TF)–factor VIIa (FVIIa) pathway, as the alveolar epithelium has been found to initiate TF-dependent intra-alveolar coagulation in response to inflammation.8 Patients with ARDS …
Effect of increased vascular pressure on lung fluid balance in unanesthetized sheep.
Authors: A J Erdmann, T R Vaughan, K L Brigham, W C Woolverton, N C Staub
Journal: Circulation Research (1975)

In 20 unanesthetized sheep, we measured lung lymph flow and lymph and plasma protein concentrations during steady-state base-line conditions and during steady-state elevations of pulmonary microvascular hydrostatic pressure (range 3 to 23 cm H2O). In every sheep there was a base-line lung lymph flow (average 5.7 +/- 2.5 (SD) ml/hour), demonstrating that net fluid filtration occurred. The base-line lymph-plasma total protein ratio averaged 0.69 +/- 0.05, indicating a high protein osmotic pressure in the interstitial fluid at the filtration site. Lymph flow increased and lymph protein concentration decreased approximately linearly whenever hydrostatic pressure rose. A new steady-state condition was reached in 1-2 hours. The difference in plasma-to-lymph protein osmotic pressure increased by half the hydrostatic pressure increment (50% negative feedback regulation). Extravascular lung water content, measured post-mortem, did not change significantly until microvascular hydrostatic pressure more than doubled, indicating a large safety factor that protects the lungs against fluid accumulation normally. The major contributions to the safety factor appeared to be a sensitive and efficient lymph pump coupled to a washout of interstitial protein. The fluid filtration coefficient, whose calculation required many assumptions, averaged 1.64 +/- 2.65 ml/(cm H2O times hour) in the base-line condition and did not change significantly over the pressure range studied.
Predictors of Recurrence in Bipolar Disorder: Primary Outcomes From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)
Authors: Roy H. Perlis, Michael J. Ostacher, Jayendra K. Patel, Lauren B. Marangell, Hongwei Zhang, Stephen R. Wisniewski, Terence A. Ketter, David J. Miklowitz, Michael W. Otto, Laszlo Gyulai, Noreen A. Reilly-Harrington, Andrew A. Nierenberg, Gary S. Sachs, Michael E. Thase
Journal: American Journal of Psychiatry (2006)

Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines. The authors looked for the features associated with risk of recurrence.The authors examined prospective data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study for up to 24 months. For those who were symptomatic at study entry but subsequently achieved recovery, time to recurrence of mania, hypomania, mixed state, or a depressive episode was examined with Cox regression.Of 1,469 participants symptomatic at study entry, 858 (58.4%) subsequently achieved recovery. During up to 2 years of follow-up, 416 (48.5%) of these individuals experienced recurrences, with more than twice as many developing depressive episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes (118, 13.8%). The time until 25% of the individuals experienced a depressive episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence. Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic, hypomanic, or mixed episode recurrence.Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery. Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence.
Should doctors own hospitals?
Authors: John A Romley
Journal: BMJ (2015)

Financial incentives for physician owners can work against patients’ best interests

In the United States, nearly four out of five hospitals are private. As of 2010, more than 200 of these private hospitals were owned by doctors. In that same year the US Congress passed and President Obama signed into law the Affordable Care Act, a comprehensive package of healthcare reforms that prohibited (with limited exceptions) further development of “physician owned hospitals” (POHs).

The American Hospital Association supported this prohibition, stating: “When a doctor self-refers a patient to a hospital in which he or she is invested, that is fundamentally the wrong incentive and leads to the wrong behavior.”1

From this critical perspective, the linked paper by Blumenthal and colleagues (doi:10.1136/bmj.h4466) examines the performance of POHs in the US in 2010.2 Specifically, the authors compared the quality of care, cost of care, and patient population at POHs with those at non-POHs located within the same hospital referral regions.

Overall, POHs look largely benign in this study. In terms of quality, POHs were indistinguishable from non-POHs in the same region in a publicly reported patient satisfaction survey, and in the provision of appropriate care for patients with heart attack, heart failure, and …
Thrombin stimulates tissue plasminogen activator release from cultured human endothelial cells.
Authors: E G Levin, U Marzec, J Anderson, L A Harker
Journal: Journal of Clinical Investigation (1984)

The effect of thrombin on the release of tissue plasminogen activator from endothelial cells was studied in primary cultures of human umbilical vein endothelial cells. Tissue plasminogen activator concentration in conditioned medium was measured by a two-site radioimmunometric assay. The addition of increasing concentrations (0.01 to 10 U/ml) of thrombin to confluent cultures produced a saturable, dose-dependent increase in the rate of release of tissue plasminogen activator. A sixfold increase in tissue plasminogen activator concentration (from 2 to 12 ng/ml) occurred after the addition of 1 U/ml thrombin (8 X 10(-9) M) to cultures containing 5 X 10(4) cells/cm2. Enhanced release was not observed until 6 h after thrombin addition, reached a maximum rate of 1.3 ng/ml per h between 8 and 16 h, and then declined to 0.52 ng/ml per h after 16 h. The 6-h lag period before increased tPA release was reproducible and independent of thrombin concentration. Thrombin inactivated with diisopropylfluorophosphate or hirudin did not induce an increase in tissue plasminogen activator levels. A 50-fold excess of diisopropylfluorophosphate-treated thrombin, which inhibits binding of active thrombin to endothelial cell high affinity binding sites, did not inhibit the thrombin-induced increase. It is concluded that proteolitically active thrombin causes an increase in the rate of release of tissue plasminogen activator from cultured human endothelial cells. The 6-h interval between thrombin treatment and enhanced tissue plasminogen activator release may reflect a delaying mechanism that transiently protects hemostatic plugs from the sudden increase in the local concentration of this fibrinolytic enzyme.
Real time high resolution magnetic resonance imaging for the assessment of gastric motility disorders
Authors: W Ajaj
Journal: Gut (2004)

<b>Background:</b> The aim of this study was to evaluate whether patients with increased or decreased gastric motility can be differentiated from healthy volunteers by means of real time magnetic resonance imaging (MRI). <b>Patients and methods:</b> Ten healthy volunteers, 10 patients with gastroparesis, and 10 patients with functional pylorospasm/peptic pyloric stenosis underwent real time MRI. All patients were examined on two separate days; once prior to therapy and once after adequate therapy. Antral motility was quantified by calculating the gastric motility index. <b>Results:</b> Patients with gastroparesis showed a lower motility index compared with the reference volunteer group while the mean motility index of the patient group with pylorospasm was more than three times higher than that of the reference value of the volunteer group. However, the gastric motility index in the patient group with gastroparesis increased, and in the group with functional pylorospasm/peptic pyloric stenosis it decreased significantly after therapy. <b>Conclusion:</b> Real time MRI is a reliable tool for assessment of gastric motion. Furthermore, differences in gastric motility index in patients with increased or decreased gastric motility could be evaluated and quantified. Due to the non-invasive character of MRI, this imaging modality may be an attractive alternative to conventional invasive diagnostic tools for gastric motility disorders and therapeutic monitoring.
Lifestyle perception and physical activity practice
Authors: Luís Raia, Joana André, João Carvalho, João Martins, Adilson Marques, Francisco Carreiro da Costa
Journal: British Journal of Sports Medicine (2011)

The aim of this study was to examine the relationship between perception of lifestyle and the practice of physical activity (PA). A total of 1158 men (44±8 y) and 1560 women (43±8 y), aged 21–90 y participated in this study. The data was assessed by a questionnaire about PA participation with and without supervision. Participants were asked to rate their lifestyle perception and health on a 5-point Likert scale range from 1 (sedentary) to 5 (very active). T-test and Pearson's correlation were used to analyse the data. On average participants reported to practise PA 2.9±3.1 times/week and 183±214 min/week. The high SDs show the wide dispersion of the results in both sexes. No difference was found between men and women regarding the number of times they practiced PA (3.0±3.1 vs 2.9±3.1 times/week, p =0.431). Men reported to practice PA during more time than women (209±235 vs 162±194 min/week) and the difference was significant ( p &lt;0.001). Although women indicated to practice PA for less time than men, they had a significant better perception of their lifestyle (men 3.21±1.04, women 3.37±1.03, p &lt;0.001). In both sexes there was a positive and significant correlation between the number of times they practice PA and the perception of lifestyle (r=0.335, p &lt;0.001; r=0.284, p &lt;0.001). The same was observed for the time they expended practicing PA per week and the perception of lifestyle (r=0.353, p &lt;0.001; r=0.290, p &lt;0.001). Looking at the correlation of perception of lifestyle and perception of health it was also found a positive and significant correlation (r=0.317, p &lt;0.001; r=0.242, p &lt;0.001). Although men and women shown no difference regarding the number of times they practice PA, men tend to practice PA longer than women. Women perceive themselves as more active than they really are. It is clear a relationship between PA and perception of lifestyle, however, for men the correlation was slightly stronger than for the women.
Diversity, Origin, and Distribution of Retrotransposons (gypsy and copia) in Conifers
Authors: Nikolai Friesen, Andrea Brandes, John Seymour (Pat) Heslop-Harrison
Journal: Molecular Biology and Evolution (2001)

We examined the diversity, evolution, and genomic organization of retroelements in a wide range of gymnosperms. In total, 165 fragments of the reverse transcriptase (RT) gene domain were sequenced from PCR products using newly designed primers for gypsy-like retrotransposons and well-known primers for copia-like retrotransposons; representatives of long interspersed nuclear element (LINE) retroposons were also found. Gypsy and copia-like retroelements are a major component of the gymnosperm genome, and in situ hybridization showed that individual element families were widespread across the chromosomes, consistent with dispersion and amplification via an RNA intermediate. Most of the retroelement families were widely distributed among the gymnosperms, including species with wide taxonomic separation from the Northern and Southern Hemispheres. When the gymnosperm sequences were analyzed together with retroelements from other species, the monophyletic origin of plant copia, gypsy, and LINE groups was well supported, with an additional clade including badnaviral and other, probably virus-related, plant sequences as well as animal and fungal gypsy elements. Plant retroelements showed high diversity within the phylogenetic trees of both copia and gypsy RT domains, with, for example, retroelement sequences from Arabidopsis thaliana being present in many supported groupings. No primary branches divided major taxonomic clades such as angiosperms, monocotyledons, gymnosperms, or conifers or (based on smaller samples) ferns, Gnetales, or Sphenopsida (Equisetum), suggesting that much of the existing diversity was present early in plant evolution, or perhaps that horizontal transfer of sequences has occurred. Within the phylogenetic trees for both gypsy and copia, two clearly monophyletic gymnosperm/conifer clades were revealed, providing evidence against recent horizontal transfer. The results put the evolution of the large and relatively conserved genome structure of gymnosperms into the context of the diversity of other groups of plants.
Responsiveness of the VISA-P scale for patellar tendinopathy in athletes
Authors: Sergio Hernandez-Sanchez, Ma Dolores Hidalgo, Antonia Gomez
Journal: British Journal of Sports Medicine (2012)

Background Patient-reported outcome measures are increasingly used in sports medicine to assess results after treatment, but interpretability of change for many instruments remains unclear. Objective To define the minimum clinically important difference (MCID) for the Victorian Institute of Sport Assessment scale (VISA-P) in athletes with patellar tendinopathy (PT) who underwent conservative treatment. Methods Ninety-eight athletes with PT were enrolled in the study. Each participant completed the VISA-P at admission, after 1 week, and at the final visit. Athletes also assessed their clinical change at discharge on a 15-point Likert scale. We equated important change with a score of ≥3 (somewhat better). Receiver-operating characteristic (ROC) curve analysis and mean change score were used to determine MCID. Minimal detectable change was calculated. The effect of baseline scores on MCID and different criteria used to define important change were investigated. A Bayesian analysis was used to establish the posterior probability of reporting clinical changes related to MCID value. Results Athletes with PT who showed an absolute change greater than 13 points in the VISA-P score or 15.4–27% of relative change achieved a minimal important change in their clinical status. This value depended on baseline scores. The probability of a clinical change in a patient was 98% when this threshold was achieved and 45% when MCID was not achieved. Conclusions Definition of the MCID will enhance the interpretability of changes in the VISA-P score in the athletes with PT, but caution is required when these values are used.
Biochemical and Structural Evidence for Pig Myocardium Adherens Junction Disruption by Cardiopulmonary Bypass
Authors: Cesario Bianchi, Eugenio G. Araujo, Kaori Sato, Frank W. Sellke
Journal: Circulation (2001)

Given that cardiopulmonary bypass (CPB) is associated with edema and heart dysfunction and that adherens junctions may regulate vascular permeability barrier integrity and cardiomyocyte function, we investigated adherens junction protein steady-state levels in a pig model of CPB.Pigs were subjected to normothermic CPB for 90 minutes, followed by post-CPB perfusion for 90 minutes. Atrial and ventricular myocardium tissue samples were harvested before institution of bypass (basal levels) and at the end of post-CPB perfusion. Adherens junctions were analyzed by either total lysate or cadherin immunoprecipitates that were immunoblotted for pan-cadherin, VE-cadherin, beta-catenin, and gamma-catenin. Adherens junction solubility was addressed with Triton X-100 extraction. Frozen tissue sections were labeled with the same antibodies, and adherens junctions were visualized by confocal microscopy. Immunoblotting of total lysates revealed an increase in smaller-molecular-weight fragments of VE-cadherin, beta-catenin, and gamma -catenin after post-CPB perfusion, indicating partial protein degradation. Smaller-molecular-weight fragments recognized by VE-cadherin and beta-catenin antibodies were also obtained from VE-cadherin immunoprecipitation, indicating degradation of endothelial cell adherens junctions. A prominent increase in adherens junction complex solubility was observed in post-CPB perfusion samples. Confocal microscopy of hearts obtained before CPB showed a continuous, homogeneous pattern of cell-cell labeling that contrasted with an irregular, discontinuous, punctuate, or zigzag pattern observed in post-CPB perfusion samples, corroborating biochemical data.These results indicate that CPB is associated with signs of degradation of endothelial and cardiomyocytes adherens junctions, pointing to a molecular mechanism leading to increased vascular permeability and cardiomyocyte dysfunction.
Bronchial Inflammation and Colonization in Patients with Clinically Stable Bronchiectasis
Authors: JOAQUIM ANGRILL, CARLES AGUSTÍ, ROSA DE CELIS, XAVIER FILELLA, ANA RAÑÓ, MONTSERRAT ELENA, JORDI PUIG DE LA BELLACASA, ANTONI XAUBET, ANTONI TORRES
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To evaluate the bronchial inflammatory response and its relationship to bacterial colonization in bronchiectasis, we performed a bronchoalveolar lavage (BAL) in 49 patients in stable clinical condition and in nine control subjects. BAL was processed for differential cell count, quantitative bacteriologic cultures, and measurement of inflammatory mediators. An increase was observed in the percentage of neutrophils (37 [0 to 98]) (median[range]) versus 1[0 to 4]%, p = 0.01), in the concentration of elastase (90.5 [8 to 2,930] versus 34 [9 to 44], p = 0.03), myeloperoxidase (9.1 [0 to 376] versus 0.3 [0.1 to 1.4], p = 0.01), and in the levels of TNF- α (4 [0 to 186] versus 0 [0 to 7], p = 0.03), IL-8 (195 [0 to 5,520] versus 3 [0 to 31], p = 0.001), and IL-6 (6 [0 to 115] versus 0 [0 to 3], p = 0.001) in patients with bronchiectasis compared with control subjects. Noncolonized patients showed a more intense bronchial inflammatory reaction than did control subjects. This inflammatory reaction was exaggerated in patients colonized by microorganisms with potential pathogenicity (MPP), with a clear relationship with the bronchial bacterial load. Patients with bronchiectasis showed a slight systemic inflammatory response, with poor correlations between systemic and bronchial inflammatory mediators, suggesting that the inflammatory process was mostly compartmentalized. We conclude that patients with bronchiectasis in a stable clinical condition present an active neutrophilic inflammation in the airways that is exaggerated by the presence of MPP, and the higher the bacterial load the more intense the inflammation.
The Long Road to Patient Safety
Authors: Daniel R. Longo, John E. Hewett, Bin Ge, Shari Schubert
Journal: JAMA (2005)

Since the Institute of Medicine (IOM) reports on medical errors and quality, national attention has focused on improving patient safety through changes in "systems" of care. These reports resulted in a new paradigm that, rather than centering on individual errors, focuses on the "systems" necessary to facilitate and enhance quality and protect patients.To assess the status of hospital patient safety systems since the release of the IOM reports and to identify changes over time in 2 states that collaborated on a patient safety project funded by the Agency for Healthcare Research and Quality.Survey of all acute care hospitals in Missouri and Utah at 2 points in time, in 2002 and 2004, using a 91-item comprehensive questionnaire (n = 126 for survey 1 and n = 128 for survey 2). To assess changes over time, we also studied the cohort of 107 hospitals that responded to both surveys.Responses to the 91-question survey as well as changes in responses to the survey questions over an 18-month period. Seven latent variables were constructed to represent the most important patient safety constructs studied: computerized physician order entry systems, computerized test results, and assessments of adverse events; specific patient safety policies; use of data in patient safety programs; drug storage, administration, and safety procedures; manner of handling adverse event/error reporting; prevention policies; and root cause analysis. For each hospital, the 7 latent variables were summed to give an overall measure of the patient safety status of the hospital.Development and implementation of patient safety systems is at best modest. Self-reported regression in patient safety systems was also found. While 74% of hospitals reported full implementation of a written patient safety plan, nearly 9% reported no plan. The area of surgery appears to have the greatest level of patient safety systems. Other areas, such as medications, with a long history of efforts in patient safety and error prevention, showed improvements, but the percentage of hospitals with various safety systems was already high at baseline for many systems. Some findings are surprising, given the overall trends; for example, while a substantial percentage of hospitals have medication safety systems, only 34.1% [corrected] reported full implementation at survey 2 of computerized physician order entry systems for medications, despite the growth of computer technology in general and in hospital billing systems in particular.The current status of hospital patient safety systems is not close to meeting IOM recommendations. Data are consistent with recent reports that patient safety system progress is slow and is a cause for great concern. Efforts for improvement must be accelerated.