tbuckley/cabot-search huggingface dataset:
A8.12 AAV mediated expression of CD39 and CD73 is effective in reducing inflammation in the air pouch synovial inflammation model
Authors: JD Finn, S Snoek, J van Ittersum, N Broekstra, C Braam, E Kramer, M van Geldorp, PP Tak, MJ Vervoordeldonk
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> The conversion of extracellular ATP (eATP) to adenosine is an important mechanism of immune suppression through the coordinated activity of two enzymes, CD39 and CD73. CD39 is a membrane bound ATPase, and CD73 is a membrane bound ectonucleotidase that converts AMP to adenosine. We have previously presented evidence that the balance between pro-inflammatory eATP and anti-inflammatory adenosine is skewed in the synovial compartment of rheumatoid arthritis patients. Here we investigated the efficacy of Adeno-associated viral type 5 (AAV5) vector mediated expression of CD39 and CD73 on <i>in vitro</i>and <i>in vivo</i>inflammation models. <h3>Materials and methods</h3> Adeno-associated viral (AAV) vectors expressing CD39 or CD73 were generated and used to transduce HEK 293 cells or RA fibroblast-like synoviocytes (FLS) and these transduced cells were co-cultured with LPS-activated human monocytes (THP-1) in the presence of ATP. Pro-inflammatory cytokine/chemokine (IL-6, CCL2) production was measured by ELISA. <i>In vivo</i> efficacy of AAV5-CD39-CD73 was investigated using the air pouch synovial inflammation (APSI) model in Balb/c mice using LPS as inflammatory stimulus. Pro-inflammatory cytokines (CCL2, IL-6) were measured by ELISA. <h3>Results</h3> HEK 293 cells and RA FLS cell lines transduced with CD39-and/or CD73-expressing AAV5 vectors demonstrated high CD39 and CD73 activity. THP-1 cells stimulated with LPS showed lower levels (&gt;80% reduction p = &lt;0.05) of IL-6 and CCL2 secretion when co-cultured with CD39 and CD73 expressing HEK293 cells or FLS cells in the presence of ATP. AAV mediated expression of CD39 and CD73 in the air pouch membrane resulted in significant decreases in pro-inflammatory cytokine levels at 24 h (˜35% reduced CCL2 p &lt; 0.05) and 48 h (25% reduced CCL2 levels p &lt; 0.05, 80% reduced IL-6 levels p &lt; 0.001) post LPS administration. <h3>Conclusion</h3> Together, these data suggest that AAV mediated expression of CD39 and CD73 may be a novel strategy for the treatment of inflammatory disease, including RA.
Diuretics in the elderly: how safe?
Authors: W J MacLennan
Journal: BMJ (1988)

Diuretics in the elderly: how safe?Around one fifth of people over 65 take diuretics.'Not surprisingly, therefore, diuretics are the commonest cause of adverse drug reactions in old age.2One of the most serious side effects is hyponatraemia, which occurs in about one fifth ofold people taking diuretics.In severe cases it causes a range of problems that includes weakness, confusion, postural giddiness, postural hypotension, falls, transient hemiparesis, and fits.3Old people also have a diminished renal reserve so that in them diuretics are more likely to precipitate a prerenal uraemia than in younger people.4The effect of diuretics on potassium balance is more contentious.Around one in 20 elderly patients taking diuretics have hypokalaemia,3 but the effect of diuretics on intracellular potassium concentrations is less dramatic.5Hypokalaemia may increase the risk of cardiac arrhythmias, but in patients with uncomplicated hypertension the risk is minimal.6The problem is more critical for patients taking cardiac glycosides because hypokalaemia greatly accentuates the cardiotoxicity of these agents.7 Claims that a low dietary intake of potassium in the elderly gives rise to muscle weakness have not been substantiated.8Diuretics also have some less immediate metabolic effects.These include hyperuricaemia, which in elderly women and less often in men gives rise to a low grade tophaceous gout.9Serum cholesterol concentrations may also rise, but the effect is transient-and there is no evidence that it increases the risk of cardiovascular disease.'0The effect of diuretics on
Home based cardiac rehabilitation
Authors: A. M Clark
Journal: BMJ (2010)

An effective way of widening access to preventative services

In the linked systematic review (doi:10.1136/bmj.b5631), Dalal and colleagues assess the effect of home based cardiac rehabilitation on mortality and morbidity, health related quality of life, and modifiable cardiac risk factors in patients with coronary heart disease.1 They found that home based cardiac rehabilitation was as effective and efficient as centre based rehabilitation at reducing mortality and cardiac events; improving risk factors such as exercise capacity, systolic blood pressure, and total cholesterol; and increasing health related quality of life. This finding is consistent with another recent meta-analysis,2 which found that home based programmes provided by “telehealth” show promise in reducing mortality and can lead to clinically significant benefits in cholesterol, blood pressure, and prevalence of smoking.2 As with centre based programmes,3 4 a variety of home based programmes can improve health and quality of life outcomes in suitable patients.

Providing programmes in the patient’s home makes sense because of what is needed for risk factor reduction. To improve morbidity and mortality, health behaviours must be sustained for at least two years.4 Home based programmes can provide support for these behaviours longer than …
Toxocaral Visceral Larva Migrans
Authors: Peter M. Schantz, Lawrence T. Glickman
Journal: New England Journal of Medicine (1978)

CERTAIN parasitic helminths of lower animals are capable of infecting a variety of mammalian species that are not their definitive hosts. Under such conditions the invading larvae usually do not develop further but may survive indefinitely in the tissues. If these animals form part of the food chain of the definitive host, the parasite's life cycle is eventually completed. When human beings are accidentally infected with these worms, severe, irreversible or even fatal damage may result. Although several scientists speculated previously that man could be infected by these parasites, it was not until 1952 that larvae of Toxocara canis, . . .
Research and work abroad are discouraged in UK's new training agenda
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

The Federation of the Royal Colleges of Physicians of the UK has warned that there is no guarantee of how many posts will be available in the new specialist training programmes in medicine that are due to start in August 2007.

It is also discouraging trainees wishing to spend some time being trained abroad, because of difficulty trainees have in providing evidence of exactly what type of training they have gained. “Those trainees currently working abroad, e.g. in Australia, should consider returning to posts in the UK by the summer of 2006,” it says in a statement.

The messages come as the federation released what it describes as its “preferred option” for new programmes to …
Relationships Among Intravascular Volume, Total Body Sodium, Arterial Pressure, and Vasomotor Tone
Authors: HIDEO TAKAGI, HARRIET P. DUSTAN, IRVINE H. PAGE
Journal: Circulation Research (1961)

In rats made hyponatremic, hypovolemic, and hypotensive by intraperitoneal injections of 5 per cent glucose solution, arterial pressure was returned to control values by correction of the intravascular-volume deficit with either 5 per cent salt-free albumin or small volumes of hypertonic sodium-chloride solution. In the former, severe hyponatremia persisted; in the latter, it was corrected. Isotonic sodium-chloride solution, given in amounts considered sufficient to repair the extracellular-fluid and electrolyte deficits, was not so effective either in controlling hypotension or in expanding the intravascular volume. Using the height of the norepinephrine pressor response and the duration of the serotonin depressor phase as estimates of sympathetic activity, sympathetic vasomotor tone was found to be enhanced during hyponatremic, hypovolemic hypotension and depressed by administration of 5 per cent albumin, hypertonic and isotonic sodium-chloride solutions. These changes in estimates of sympathetic activity seemed dependent on changes in intravascular volume and not in extracellular sodium concentrations. Experiments performed following pentolinium-induced ganglion blockade showed that the depressor phase of the serotonin response was dependent on sympathetic vasomotor outflow, but that the height of norepinephrine pressor response was dependent not only on sympathetic activity, but also on the intravascular volume. In this study of selective sodium deficit, intravascular volume was found to be an important determinant of arterial pressure and sympathetic vasomotor tone.
Villous Adenoma of the Duodenum: Endoscopic diagnosis and resection
Authors: J. Dupas, R. Marti, J. Capron, J. Delamarre
Journal: Endoscopy (1977)

The authors report a new case of villous adenoma of the duodenum diagnosed by X-ray examination and duodenoscopy. Endoscopic removal allows an accurate histologic diagnosis. This endoscopic resection relieves symptoms and spares the patient a laparotomy. It seems to be an acceptable treatment of benign duodenal tumors.
A Learner-Centered Diabetes Management Curriculum
Authors: Daniel J. DeSalvo, Larrie W. Greenberg, Celia L. Henderson, Fran R. Cogen
Journal: Diabetes Care (2012)

Diabetes errors, particularly insulin administration errors, can lead to complications and death in the pediatric inpatient setting. Despite a lecture-format curriculum on diabetes management at our children's hospital, resident diabetes-related errors persisted. We hypothesized that a multifaceted, learner-centered diabetes curriculum would help reduce pathway errors.The 8-week curricular intervention consisted of 1) an online tutorial addressing residents' baseline diabetes management knowledge, 2) an interactive diabetes pathway discussion, 3) a learner-initiated diabetes question and answer session, and 4) a case presentation featuring embedded pathway errors for residents to recognize, resolve, and prevent. Errors in the 9 months before the intervention, as identified through an incident reporting system, were compared with those in the 10 months afterward, with errors classified as relating to insulin, communication, intravenous fluids, nutrition, and discharge delay.Before the curricular intervention, resident errors occurred in 28 patients (19.4% of 144 diabetes admissions) over 9 months. After the intervention, resident errors occurred in 11 patients (6.6% of 166 diabetes admissions) over 10 months, representing a statistically significant (P = 0.0007) decrease in patients with errors from before intervention to after intervention. Throughout the study, the errors were distributed into the categories as follows: insulin, 43.8%; communication, 39.6%; intravenous fluids, 14.6%; nutrition, 0%; and discharge delay, 2.1%.An interactive learner-centered diabetes curriculum for pediatric residents can be effective in reducing inpatient diabetes errors in a tertiary children's hospital. This educational model promoting proactive learning has implications for decreasing errors across other medical disciplines.
Factors Associated With the Disposition of Severely Injured Patients Initially Seen at Non–Trauma Center Emergency Departments
Authors: M. Kit Delgado, Michael A. Yokell, Kristan L. Staudenmayer, David A. Spain, Tina Hernandez-Boussard, N. Ewen Wang
Journal: JAMA Surgery (2014)

Trauma is the leading cause of potential years of life lost before age 65 years in the United States. Timely care in a designated trauma center has been shown to reduce mortality by 25%. However, many severely injured patients are not transferred to trauma centers after initially being seen at non–trauma center emergency departments (EDs).To determine patient-level and hospital-level factors associated with the decision to admit rather than transfer severely injured patients who are initially seen at non–trauma center EDs and to ascertain whether insured patients are more likely to be admitted than transferred compared with uninsured patients.Retrospective analysis of the 2009 Nationwide Emergency Department Sample. We included all ED encounters for major trauma (Injury Severity Score, >15) seen at non–trauma centers in patients aged 18 to 64 years. We excluded ED discharges and ED deaths. We quantified the absolute risk difference between admission vs transfer by insurance status, while adjusting for age, sex, mechanism of injury, Injury Severity Score, weekend admission and month of visit, and urban vs rural status and median household income of the home zip code, as well as annual ED visit volume and teaching status and US region.Inpatient admission vs transfer to another acute care facility.In 2009, a total of 4513 observations from 636 non–trauma center EDs were available for analysis, representing a nationally weighted population of 19,312 non–trauma center ED encounters for major trauma. Overall, 54.5% in 2009 were admitted to the non–trauma center. Compared with patients without insurance, the adjusted absolute risk of admission vs transfer was 14.3% (95% CI, 9.2%-19.4%) higher for patients with Medicaid and 11.2% (95% CI, 6.9%-15.4%) higher for patients with private insurance. Other factors associated with admission vs transfer included severe abdominal injuries (risk difference, 15.9%; 95% CI, 9.4%-22.3%), urban teaching hospital vs non–teaching hospital (risk difference, 26.2%; 95% CI, 15.2%-37.2%), and annual ED visit volume (risk difference, 3.4%; 95% CI, 1.6%-5.3% higher for every additional 10,000 annual ED visits).Patients with severe injuries initially evaluated at non–trauma center EDs were less likely to be transferred if insured and were at risk of receiving suboptimal trauma care. Efforts in monitoring and optimizing trauma interhospital transfers and outcomes at the population level are warranted.
Psychophysiological Correlates of Relaxation Induced by Standard Autogenic Training
Authors: Norio Mishima, Shinya Kubota, Shoji Nagata
Journal: Psychotherapy and Psychosomatics (1999)

&lt;i&gt;Background:&lt;/i&gt; The present study aimed to determine the psychophysiological changes induced in subjects by standard autogenic training (AT). Physiological measurements were taken under strict experimental conditions. &lt;i&gt;Methods:&lt;/i&gt; Thirty-one healthy students were divided randomly into two groups: the AT group and the control group. In the first session, the physiological variables were measured for all students before and after all were asked to relax in their own way. The AT group were then taught AT for 3 months, after which time the measurements were repeated. In the second session, the AT group practised the standard AT exercise, while the control group repeated their own form of simple relaxation. Electrocardiogram, plethysmogram (PTG) and blood pressure (BP) were measured while the students carried out a breathing rate of 15 cycles/min. The R-R intervals and BP were analysed by an autoregressive model for spectral analysis, and the data were compared by repeated-measures ANOVA. &lt;i&gt;Results:&lt;/i&gt; The AT group had a significant increase in the mean R-R interval and a significant decrease in the baseline deflection of the PTG in the second session. There were no significant changes in sympathetic activity except for the change in the PTG, although low frequency amplitude of systolic BP decreased slightly. &lt;i&gt;Conclusions:&lt;/i&gt; AT was found to induce significant changes that were independent of respiration in healthy students, although paced breathing might have operated as a mental stress. The increase in mean R-R interval and the decrease in baseline deflection of the PTG were the most robust correlates of AT.
Early Bactericidal Activity and Sterilizing Activity of Ciprofloxacin in Pulmonary Tuberculosis: To the Editor
Authors: Denis A. Mitchison
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

"Early Bactericidal Activity and Sterilizing Activity of Ciprofloxacin in Pulmonary Tuberculosis: To the Editor." American Journal of Respiratory and Critical Care Medicine, 151(3_pt_1), p. 921
Physical Training Increases Endothelial Progenitor Cells, Inhibits Neointima Formation, and Enhances Angiogenesis
Authors: Ulrich Laufs, Nikos Werner, Andreas Link, Matthias Endres, Sven Wassmann, Kristina Jürgens, Eckart Miche, Michael Böhm, Georg Nickenig
Journal: Circulation (2003)

Background— The molecular mechanisms by which physical training improves peripheral and coronary artery disease are poorly understood. Bone marrow–derived endothelial progenitor cells (EPCs) are thought to exert beneficial effects on atherosclerosis, angiogenesis, and vascular repair. Methods and Results— To study the effect of physical activity on the bone marrow, EPCs were quantified by fluorescence-activated cell sorter analysis in mice randomized to running wheels (5.1±0.8 km/d, n=12 to 16 per group) or no running wheel. Numbers of EPCs circulating in the peripheral blood of trained mice were enhanced to 267±19%, 289±22%, and 280±25% of control levels after 7, 14, and 28 days, respectively, accompanied by a similar increase of EPCs in the bone marrow and EPCs expanded from spleen-derived mononuclear cells. eNOS −/− mice and wild-type mice treated with N G -nitro- l -arginine methyl ester showed lower EPC numbers at baseline and a significantly attenuated increase of EPC in response to physical activity. Exercise NO dependently increased serum levels of vascular endothelial growth factor and reduced the rate of apoptosis in spleen-derived EPCs. Running inhibited neointima formation after carotid artery injury by 22±2%. Neoangiogenesis, as assessed in a subcutaneous disc model, was increased by 41±16% compared with controls. In patients with stable coronary artery disease (n=19), moderate exercise training for 28 days led to a significant increase in circulating EPCs and reduced EPC apoptosis. Conclusions— Physical activity increases the production and circulating numbers of EPCs via a partially NO-dependent, antiapoptotic effect that could potentially underlie exercise-related beneficial effects on cardiovascular diseases.
Bepotastine Besilate Ophthalmic Solution 1.5% Reduces Nonocular Composite Symptom (NOCS) Scores 16 Hours Following Dosing in the Conjunctival Allergen Challenge (CAC) Model of Allergic Conjunctivitis
Authors: J.A. Gow, T.T. Macejko, M.T. Bergmann, E. Meier, M.B. Abelson, J.I. Williams, T.R. McNamara
Journal: Journal of Allergy and Clinical Immunology (2011)
Survivin-3B Potentiates Immune Escape in Cancer but Also Inhibits the Toxicity of Cancer Chemotherapy
Authors: Frédérique Végran, Romain Mary, Anne Gibeaud, Céline Mirjolet, Bertrand Collin, Alexandra Oudot, Céline Charon-Barra, Laurent Arnould, Sarab Lizard-Nacol, Romain Boidot
Journal: Cancer Research (2013)

Dysregulation in patterns of alternative RNA splicing in cancer cells is emerging as a significant factor in cancer pathophysiology. In this study, we investigated the little known alternative splice isoform survivin-3B (S-3B) that is overexpressed in a tumor-specific manner. Ectopic overexpression of S-3B drove tumorigenesis by facilitating immune escape in a manner associated with resistance to immune cell toxicity. This resistance was mediated by interaction of S-3B with procaspase-8, inhibiting death-inducing signaling complex formation in response to Fas/Fas ligand interaction. We found that S-3B overexpression also mediated resistance to cancer chemotherapy, in this case through interactions with procaspase-6. S-3B binding to procaspase-6 inhibited its activation despite mitochondrial depolarization and caspase-3 activation. When combined with chemotherapy, S-3B targeting in vivo elicited a nearly eradication of tumors. Mechanistic investigations identified a previously unrecognized 7-amino acid region as responsible for the procancerous properties of survivin proteins. Taken together, our results defined S-3B as an important functional actor in tumor formation and treatment resistance.
FIBROLIPOMA OF LEFT LABIUM MAJUS
Authors: WILLIAM R. LOVELACE
Journal: JAMA (1923)

Lipoma of the vulva is of sufficiently rare occurrence to make the report of a case worth while.  REPORT OF CASE  A widow, aged 40, who had given birth to two children, both normal deliveries, was a native of New Mexico. There was nothing in the family or personal history which had any bearing on the condition under discussion. Except for the  Examination.  —The patient was well nourished, 5 feet, 6 inches tall, and weighed 200 pounds. The blood pressure was systolic, 130; diastolic, 85. The abdomen was flat and without rigidity. No tumor masses could be felt anywhere. All the organs were normal and appeared to be functioning properly. The appetite was good, and the patient suffered no pain before or after eating. She said that she slept well. The knee jerks were slightly increased; all other reflexes were normal.  Suspended from the left labium majus was a pedunculated
REMOVAL OF THE OSSICLES, WITH REPORT OF SIX CASES.
Authors: NORVAL H. PIERCE
Journal: JAMA (1898)

<h3>Case 1.—Chronic sclerosing inflammation of the middle ear.</h3> J. B., a negro, age 25, employed as a waiter. His general condition is good, but there is a rheumatic diathesis. His previous history is of but little value. Has had little or no treatment. Has steadily increasing deafness which became apparent in the left ear first, about three years previously. This has become so great that it seriously interferes with the proper peformance of his vocation. There is arterial tinnitus but he complained of it only when questioned. There has been no pain; no discharge. The deafness has become decidedly worse during the preceding four months. Auricles and external canals normal, except for the absence of cerumen in the latter. Tympanic membranes pale; mobility slightly decreased; not depressed. Light reflexes quite normal. Handles of mallei were defined through their entire lengths. The Eustachian tube only slightly occluded; that on the right
Rebuttal from Authors re: Urs E. Studer, Laurence Collette. Morbidity from Pelvic Lymphadenectomy in Men Undergoing Radical Prostatectomy. Eur Urol 2006;50:887–9.
Authors: Alberto Briganti, Pierre I. Karakiewicz, Felix K.-H. Chun, Francesco Montorsi
Journal: European Urology (2006)
Unilateral Breast Enlargement
Authors: Guenter Topf
Journal: JAMA (1977)

SINCE hemodialysis has become a routine treatment for patients with end-stage renal disease, the surgically created arteriovenous (AV) fistula, first described by Brescia and Cimino in 1966, has become the vascular access of choice in most patients. In general, it is relatively simple and safe; but with an increasing number of these procedures being performed, one might anticipate an increasing prevalence of complications. We report ipsilateral breast enlargement developing with the maturation of such a fistula and finally necessitating surgical closure of the fistula. <h3>Report of a Case</h3> A 71-year-old woman was found to have chronic renal failure in 1970 thought to be secondary to chronic pyelonephritis. An AV fistula (end of cephalic vein to side of radial artery) was created in her left forearm in March 1975, when her creatinine clearance was 8 ml/min; serum creatinine level, 5.1 mg/100 ml; and blood urea nitrogen level, 45 mg/100 ml. In