tbuckley/cabot-search huggingface dataset:
LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis
Authors: Takahiro Nakamura, Junji Hamuro, Mikiro Takaishi, Szandor Simmons, Kazuichi Maruyama, Andrea Zaffalon, Adam J. Bentley, Satoshi Kawasaki, Maho Nagata-Takaoka, Nigel J. Fullwood, Satoshi Itami, Shigetoshi Sano, Masaru Ishii, Yann Barrandon, Shigeru Kinoshita
Journal: Journal of Clinical Investigation (2013)

Corneal integrity and transparency are indispensable for good vision. Cornea homeostasis is entirely dependent upon corneal stem cells, which are required for complex wound-healing processes that restore corneal integrity following epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal epithelial stem cell population and sporadically expressed in the basal cells of ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell recruitment following injury and promoted a cell-fate switch from transparent epithelium to keratinized skin-like epidermis, which led to corneal blindness. In addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1–/– mice rescued pathological phenotypes and prevented corneal opacity. Additionally, transgenic mice that expressed a constitutively active form of STAT3 in the corneal epithelium had abnormal features, including corneal plaques and neovascularization similar to that found in Lrig1–/– mice. Bone marrow chimera experiments indicated that LRIG1 also coordinates the function of bone marrow–derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis.
The use of patients for learning and maintaining practical skills
Authors: S M Yentis
Journal: Journal of the Royal Society of Medicine (2005)

Throughout their careers, doctors have an ethical obligation to consider the benefits and harms of treatment, and choose the most appropriate for each patient, resources allowing. There is also a legal requirement to practise to acceptable standards together with a professional requirement to participate in continuous medical education/professional development. The General Medical Council (GMC) states 'Doctors are responsible for maintaining their professional competence and standard of performance...'1 and 'You must keep your knowledge and skills up to date... '2. There is a corresponding duty to educate others: 'You should be willing to contribute to the education of students or colleagues.'2

A doctor's prime duty, however, is to 'Make the care of your patient your first concern'2—a duty that sits awkwardly with the other duty to learn and maintain less familiar skills that might be required for other patients. This conflict has implications for respecting patients' autonomy, gaining consent for treatments and upholding standards of practice. For example, fear of complaint or legal action motivates many anaesthetists specifically interested in airway management to stop teaching others on procedures or maintaining their own skills (debate and discussion, Difficult Airway Society Annual Meetings, Edinburgh 1999 and London 2002), despite recognized deficiencies in these skills.3 Most of their concerns relate to informed consent for specific procedures or parts thereof—even though many consider them 'routine'. Such concerns may not be unwarranted: there are discrepancies between what patients would wish to be informed about and what anaesthetists feel they should be informed about.4

The published work tends to neglect this dilemma, instead focusing on junior trainees, medical students, or practice on the recently dead,5-7 but it merits wide debate especially at a time when specialist training is being curtailed and new consultants will be short of practical experience.8,9

Here I discuss the following questions. What is a 'procedure' and how can one decide whether its components can or should be considered separately—for example, regarding consent and choice? How can doctors balance their obligations to the present patient with those to future patients and society? Do patients themselves have obligations to other patients such that they ought to participate in doctors' learning or maintenance of skills? And how can the practitioner reconcile these conflicts while respecting patients' autonomy? Finally, I offer a stepwise, practical approach based on consideration of these questions.
Effect of right ventricular pressure on the end-diastolic left ventricular pressure-volume relationship before and after chronic right ventricular pressure overload in dogs without pericardia.
Authors: W C Little, F R Badke, R A O'Rourke
Journal: Circulation Research (1984)

We studied the effect of chronic right ventricular pressure overload on diastolic ventricular interdependence in dogs without pericardia, instrumented to measure left ventricular pressure, right ventricular pressure, and 3 left ventricular dimensions. We studied 12 dogs before (control) and nine dogs after 6 weeks of pulmonary artery constriction producing systolic right ventricular pressure greater than or equal to 70 mm Hg. Compared to control, following pulmonary artery band there was greater (P less than 0.01) interventricular septal mass (53 +/- 15 vs. 35 +/- 7 mg, mean +/- SD), thickness (15 +/- 2 vs. 10 +/- 1 mm), and ratio of the surface area of the interventricular septal to total left ventricular surface area (0.38 +/- 0.03 vs. 0.33 +/- 0.02), but unchanged left ventricular free wall mass (81 +/- 12 vs. 84 +/- 14 mg) and thickness (11 +/- 2 vs. 11 +/- 2 mm). End-diastolic right and left ventricular pressures and left ventricular volume were varied by vena cava and pulmonary artery occlusions and releases. Volume was calculated as an ellipsoid and the data in each dog fit to: left ventricular pressure = a0 + a1V + a2V2 + a3V3 + a4V4 + bPRV, r greater than or equal to 0.91 in each dog. During control, b was similar, whether calculated from both pulmonary artery and vena cava occlusions (0.47 +/- 0.09) or from vena cava occlusions alone (0.43 +/- 0.11), and was greater than the ratio of the interventricular septal surface area to left ventricular surface area (0.33 +/- 0.02, P less than 0.05). Following the pulmonary artery band, b decreased to 0.21 +/- 0.10 (P less than 0.05) and was less than the ratio of interventricular septal surface area to the left ventricular surface area which increased to 0.38 +/- 0.03 (P less than 0.05). We conclude that the effect of alterations in right ventricular pressure on the end-diastolic left ventricular pressure volume relationship, independent of the pericardium, is reduced following the pulmonary artery band that produces interventricular septal hypertrophy. These results are consistent with the hypothesis that the effect of alterations of right ventricular pressure on the diastolic left ventricular pressure-volume relationship depends on the relative elastance of the interventricular septum and left ventricular free wall, and not simply on the ratio of the interventricular septal surface area to the left ventricular surface area.
Plasma Pharmacokinetics, Oral Bioavailability, and Interspecies Scaling of the DNA Methyltransferase Inhibitor, Zebularine
Authors: Julianne L. Holleran, Robert A. Parise, Erin Joseph, Julie L. Eiseman, Joseph M. Covey, Elizabeth R. Glaze, Alexander V. Lyubimov, Ya-Fei Chen, David Z. D'Argenio, Merrill J. Egorin
Journal: Clinical Cancer Research (2005)

Zebularine is a DNA methyltransferase inhibitor proposed for clinical evaluation.We developed a liquid chromatography/mass spectrometry assay and did i.v. and oral studies in mice, rats, and rhesus monkeys.In mice, plasma zebularine concentrations declined with terminal half-lives (t(1/2)) of 40 and 91 minutes after 100 mg/kg i.v. and 1,000 mg/kg given orally, respectively. Zebularine plasma concentration versus time curves (area under the curve) after 100 mg/kg i.v. and 1,000 mg/kg given orally were 7,323 and 4,935 mug/mL min, respectively, corresponding to a total body clearance (CL(tb)) of 13.65 mL/min/kg, apparent total body clearance (CL(app)) of 203 mL/min/kg, and oral bioavailability of 6.7%. In rats, plasma zebularine concentrations declined with t(1/2) of 363, 110, and 126 minutes after 50 mg/kg i.v., 250 mg/kg given orally, and 500 mg/kg given orally, respectively. Zebularine areas under the curve after 50 mg/kg i.v., 250 mg/kg given orally, and 500 mg/kg given orally were 12,526, 1,969, and 7,612 mug/mL min, respectively, corresponding to a CL(tb) of 3.99 mL/min/kg for 50 mg/kg i.v. and CL(app) of 127 and 66 mL/min/kg for 250 and 500 mg/kg given orally, respectively. Bioavailabilities of 3.1% and 6.1% were calculated for the 250 and 500 mg/kg oral doses, respectively. In monkeys, zebularine t(1/2) was 70 and 150 minutes, CL(tb) was 3.55 and 10.85 mL/min/kg after i.v. administration, and CL(app) was 886 and 39,572 mL/min/kg after oral administration of 500 and 1,000 mg/kg, respectively. Zebularine oral bioavailability was <1% in monkeys. Interspecies scaling produced the following relationship: CL(tb) = 6.46(weight(0.9)).Zebularine has limited oral bioavailability. Interspecies scaling projects a CL(tb) of 296 mL/min in humans.
Psychiatric home treatment
Authors: T. Burns
Journal: BMJ (2000)

Editor—Smyth and Hoult ask why the implementation of home treatment has been “delayed” in the United Kingdom and call for more “sophisticated evaluations” while continuing the same tired (and tiresome) polemic masquerading as science that holds up such progress.1 They present a categorical view of home treatment versus “the rest,” where only one of “the 12 features of an effective home treatment team” (several visits daily) is not available in some form in routine British mental health practice. How do Smyth and Hoult know that each of these 12 features is necessary or makes a difference? They do not. The series of studies they quote are all “black box” trials of complex and often poorly defined experimental services against even more poorly defined control services (often simply called standard care). To prove effectiveness, carefully controlled trials that vary only one component are needed. Smyth and Hoult did not quote our study (of which they were aware), which is one of the first community care studies to do this.2
History and Developmental Aspects of The Indicator-Dilution Technic
Authors: I. J. Fox
Journal: Circulation Research (1962)

Origin of Indicator-Dilution Technics• The earliest injections of indicators into the vascular system were made for the purpose of determining circulation times between various points in the circulation.Haller 1 in 1761 reported the injection of a colored liquid into the vena cava of a freshly killed animal to compare pulmonary circulation times through the inflated and collapsed lungs.In 1827 ITering-determined the circulation time in a horse by injecting a solution of potassium ferrocyanide into one jugular vein and sampling from the opposite jugular, the time of arrival of: the indicator being determined by testing successive blood samples for Prussian blue (ferric ferrocyanide).In a modification of the latter method which clearly anticipates presently used technics for discontinuous sampling of the dye-blood mixture at a particular site in the circulation following injection of an indicator dye at another site, Vierordt 3 attached a number of sampling cups to a disk which was rotated at a uniform rate so as to permit sampling at known time intervals (of 1 second).To Stewart 4 " 7 goes the credit for extending the application of indicator-dilution technics to the determination of the cardiac output and of the "central blood volume" as well as for devising the first method permitting the continuous detection of indicator concentration at the sampling site.Hypertonic saline (1.5 per cent) was the indicator that he used.The ingenious detecting instrument devised by him consisted of a pair of nonpolarizable electrodes forming one arm of a Wheatstone bridge which in turn was connected to a telephone.This enabled Stewart to detect continuously the changes in concentration of the
Are Hemoglobin Levels Elevated in Type 1 Diabetes?
Authors: Baqiyyah N. Conway, Rachel G. Miller, Trevor J. Orchard
Journal: Diabetes Care (2009)

While lower hemoglobin is generally associated with adverse events in diabetes, we have recently observed in type 1 diabetes that those with overt nephropathy had hemoglobin levels as high as 18.8 g/dl. We thus explored whether hemoglobin concentrations are generally higher in type 1 diabetes.Baseline (1986-1988) hemoglobin levels from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of type 1 diabetes were compared with general population data from the National Health and Nutrition Examination Survey (NHANES) III in the same age range as the EDC population (aged 8-48 years).Both male and female EDC study participants had significantly higher hemoglobin levels than their NHANES III counterparts (men: 16.0 vs. 15.1 g/dl, P < 0.0001; women: 14.1 vs. 13.3 g/dl, P < 0.0001). The difference between the two populations was greatest in adolescent female subjects.Hemoglobin levels may be higher in type 1 diabetes than in the general population, which may have important clinical implications.
The Painful Prescription: Rationing Hospital Care.
Journal: Annals of Internal Medicine (1984)

Britain are achieved by a simple rationing, with long queues, poor quality, and bureaucratic rigidity. Aaron and Schwartz seek to show how the practice of medicine really differs in the two countries, with a special emphasis on the use of various types of medical technology. The most valuable part of the book is a discussion of specific technologies, including dialysis and kidney transplantation, hemophilia, cancer therapies, bone marrow transplantation, total parenteral nutrition, hip replacement, coronary artery surgery, computed tomographic scanners, and diagnostic roentgenograms. In some instances, such as bone marrow transplantation and radiotherapy, the British provide services at levels comparable to those in the United States. In other instances, such as coronary artery surgery and hemodialysis, the British provide services to far fewer patients. The authors did not choose their case studies randomly. They had cer¬ tain hypotheses that they wanted to explore and therefore chose technolo¬ gies that would provide illuminating contrasts. For example, the British come close to the US model in the performance of total hip replacement surgery yet are much more conserva¬ tive in their provision of coronary artery surgery. Both are major surgi¬ cal procedures, primarily affecting the quality of life of elderly patients. Aaron and Schwartz argue that the different patterns of provision may be attributable to the more obvious disability of hip disease, its impact on other social services if untreated, and the alternative of medical therapy for those with angina. One of the most important aspects of the book is its discussion of ration¬ ing, especially for services such as hemodialysis among the elderly. Even though treatment is rarely provided to patients over the age of 65 years, there are no explicit rationing crite¬ ria, and nephrologists rarely have to turn away patients. Instead, general practitioners use implicit criteria, such as comorbidities, to provide the rationalization for their reluctance to refer patients who they know are unlikely to be treated. This incorpora¬ tion into  judgment of the availability of services has clear implications for the discussion of var¬ iations in clinical practice patterns in the United States. The current emphasis on health
THE REQUIREMENT OF SERINE ESTERASE FUNCTION IN COMPLEMENT-DEPENDENT ERYTHROPHAGOCYTOSIS
Authors: David S. Pearlman, Peter A. Ward, Elmer L. Becker
Journal: The Journal of Experimental Medicine (1969)

The p-nitrophenyl ethyl phosphonate esters have been shown to inhibit complement-dependent erythrophagocytosis when exposed to guinea pig polymorphonuclear leukocytes prior to the initiation of phagocytosis. Inhibition of phagocytosis occurred in a manner characteristic of the well-defined capacity of phosphonate esters to inactivate serine esterases: inhibition was irreversible, dependent upon the temperature of reaction and pH of the reaction medium, and proportional to the concentration of inhibitor used and the duration of exposure between leukocytes and inhibitor. Phosphonate inhibition was further shown to be independent of any general cell damaging effects of the compounds used. The phagocytic enzyme inhibited by phosphonate esters apparently exists in or on leukocytes in an already activated state prior to the initiation of the phagocytic process. The inhibitory profile of the activated phagocytic esterase was found to be essentially identical to the profile of inhibition previously obtained for the activated chemotactic esterase of rabbit polymorphonuclear leukocytes, suggesting that the same enzyme may function in both chemotaxis and phagocytosis. Various substrates including acetate esters reported to protect the activated chemotactic esterase from inhibition by phosphonate esters did not exhibit a clear protective effect in the phagocytic system and attempts to define the relationship between the two enzymes were unsuccessful. Suggestive evidence was also obtained for the requirement of the function of a second, activatable esterase in the phagocytic process.
Neurocognitive function in same-sex twins following focal radiation for medulloblastoma
Authors: Donald J. Mabbott, Marcia Barnes, Normand Laperriere, Susan H. Landry, Eric Bouffet
Journal: Neuro-Oncology (2007)

Increased neurotoxicity and poor long-term neurocognitive outcome of preschool children treated for brain tumors have led to innovative therapeutic strategies in order to delay or avoid the use of craniospinal radiation and to improve survival. Because these protocols are relatively new, few data exist regarding cognitive outcome. We conducted a twin case-control study to investigate neurocognitive and behavioral outcome in a preschool patient who was 16 months old at diagnosis of medulloblastoma and was treated with surgery, chemotherapy, stem cell transplant, and focal radiation to the tumor bed. Stability and change over two assessments were compared for the patient and her nonaffected twin for standardized measures of cognitive function and experimental measures of parent-child interaction, social competence, and goal-directed play. A striking finding was improvement in intelligence, receptive language, and visual-motor functioning in the affected twin from 12 months to 24 months after treatment. Improvement in ratings of parent-child interaction and social competence for the affected twin was also evident. These findings are notable compared with the potentially devastating impact of craniospinal tumor, and this study is among the first to document the relative benefit of focal radiation in sparing cognitive function, albeit in a single case study.
Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus
Authors: Manal M. Hassan, Lu-Yu Hwang, Chiq J. Hatten, Mark Swaim, Donghui Li, James L. Abbruzzese, Palmer Beasley, Yehuda Z. Patt
Journal: Hepatology (2002)

Risk factors associated with hepatocellular carcinoma (HCC) are well documented, but the synergisms between these risk factors are not well examined. We conducted a hospital-based, case-control study among 115 HCC patients and 230 non-liver cancer controls. Cases and controls were pathologically diagnosed at The University of Texas M. D. Anderson Cancer Center and were matched by 5-year age groups, sex, and year of diagnosis. Information on risk factors was collected by personal interview and medical records review. Blood samples were tested for the presence of antibodies to hepatitis C virus antigen (anti-HCV), hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (anti-HBc). Conditional logistic regression was used to determine odds ratios (ORs) by the maximum likelihood method. Multivariate ORs and 95% confidence intervals (CIs) were 15.3 (4.3-54.4), 12.6 (2.5-63.1), 4.5 (1.4-14.8), and 4.3 (1.9-9.9) for anti-HCV, HBsAg, heavy alcohol consumption (≥80 mL ethanol/d), and diabetes mellitus, respectively. Synergistic interactions on the additive model were observed between heavy alcohol consumption and chronic hepatitis virus infection (OR, 53.9; 95% CI, 7.0-415.7) and diabetes mellitus (OR, 9.9; 95% CI, 2.5-39.3). Independent of the effect of HCV, HBV, and diabetes mellitus, heavy alcohol consumption contributes to the majority of HCC cases (32%), whereas 22%, 16%, and 20% were explained by HCV, HBV, and diabetes mellitus, respectively. In conclusion, the significant synergy between heavy alcohol consumption, hepatitis virus infection, and diabetes mellitus may suggest a common pathway for hepatocarcinogenesis. Exploring the underlying mechanisms for such synergisms may indicate new HCC prevention strategies in high-risk individuals.
Continuous Recordings of Mixed Venous Oxygen Saturation during Weaning from Mechanical Ventilation and the Ramifications Thereof
Authors: AMAL JUBRAN, MALI MATHRU, DAVID DRIES, MARTIN J. TOBIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To define the importance of hemodynamic performance and global tissue oxygenation in determining weaning outcome, we recorded mixed venous oxygen saturation (SvO2 ) continuously in eight ventilator-supported patients who failed a trial of spontaneous breathing and 11 patients who tolerated a trial and were successfully extubated. Immediately before the weaning trial, SvO2 was not statistically different in the two groups (p = 0.28). On discontinuation of the ventilator, SvO2 fell progressively in the failure group (p < 0.01), whereas it did not change in the success group. During the trial of spontaneous breathing, O2 demand was similar in the two groups, but it differed in the manner with which it was met. The success group demonstrated an increase in cardiac index (p < 0.05) and O2 transport (p < 0.02). The failure group did not increase O2 transport, partly because of elevations in right- and left-ventricular afterload, but, instead, increased O2 extraction ratio (p < 0.02) with a consequent fall in SvO2 . In turn, the low SvO2 combined with greater venous admixture (p < 0.0006) led to rapid arterial desaturation (p < 0.006) and a relative decrease in O2 being supplied to the tissues. In conclusion, ventilator-supported patients who failed a trial of spontaneous breathing developed a progressive decrease in SvO2 caused by the combination of a relative decrease in convective O2 transport and an increase in O2 extraction by the tissues.
CILOSTAZOL INCREASES PATENCY AND DECREASES ADVERSE OUTCOMES IN PATIENTS SUBMITTED TO PERCUTANEOUS FEMOROPOPLITEAL STENT REVASCULARIZATION: A RANDOMIZED CONTROLLED TRIALS META-ANALYSIS
Authors: Alexandre M. Benjo, Daniel Garcia, James Jenkins, Rhanderson Cardoso, Taina Molina, Emad Aziz, Tyrone Collins
Journal: Journal of the American College of Cardiology (2014)