tbuckley/cabot-search huggingface dataset:
Skin fibroblasts are potent suppressors of inflammation in experimental arthritis
Authors: C. Bouffi, C. Bony, C. Jorgensen, D. Noel
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Mesenchymal stromal cells (MSC) are characterised by their capacity to suppress immune reactions. This function was reported to be shared in vitro by fibroblasts but their role has been poorly investigated in vivo. This study explored whether fibroblasts isolated from skin may suppress the host immune response in a model of autoimmune disorder. <h3>Methods and Results</h3> It was first confirmed that skin fibroblasts lack the capacity to differentiate into osteoblasts or chondrocytes but possess the capacity to inhibit in vitro the proliferation of T lymphocytes. Fibroblasts also secrete modulatory molecules, in particular prostaglandin E2 and nitric oxide, similar to MSC. To assess their role in vivo, the collagen-induced arthritis model was used, and showed that similar to MSC the intravenous injection of fibroblasts efficiently suppress clinical signs of arthritis and delay disease onset. This effect was associated with reduced inflammation as reflected by biological parameters and increased levels of IL-5, IL-10 and IL-13 in the spleens of treated mice. To characterise the mechanism of immunosuppression further, phenotypic analyses were performed and could not detect any induction of CD4 CD25 Foxp3<sup>+</sup> regulatory T (Treg) cells. A population of CD4 IL-10<sup>+</sup> T cells was, however, detected that was slightly increased after fibroblast injection and significantly upregulated after MSC administration. <h3>Conclusions</h3> This study gives the first evidence for an immunosuppressive role of fibroblasts in vivo, and strongly suggests that fibroblasts induce a T-helper type 2 immune profile, although the possibility that IL-10-secreting Treg cells may be generated cannot be excluded.
Quality assurance in endobronchial ultrasound
Authors: M. G. Slade, G. C. Slade
Journal: Thorax (2010)

In their study of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), Kemp and colleagues report variation in the learning curves for five operators, studied by using the cumulative sum (cusum) technique,1 with which we have some experience.2 The authors speculate on whether variations in lymph node size, prevalence of underlying diagnoses or rate of accrual of cases may explain these differences. We believe there may be other important influences. Successful …
Improvements in PM<sub>10</sub> Exposure and Reduced Rates of Respiratory Symptoms in a Cohort of Swiss Adults (SAPALDIA)
Authors: Christian Schindler, Dirk Keidel, Margaret W. Gerbase, Elisabeth Zemp, Robert Bettschart, Otto Brändli, Martin H. Brutsche, Luc Burdet, Werner Karrer, Bruno Knöpfli, Marco Pons, Regula Rapp, Lucy Bayer-Oglesby, Nino Künzli, Joel Schwartz, Lee-Jane S. Liu, Ursula Ackermann-Liebrich, Thierry Rochat
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Reductions in mortality following improvements in air quality were documented by several studies, and our group found, in an earlier analysis, that decreasing particulate levels attenuate lung function decline in adults.We investigated whether decreases in particulates with an aerodynamic diameter of less than 10 microm (PM10) were associated with lower rates of reporting respiratory symptoms (i.e., decreased morbidity) on follow-up.The present analysis includes 7,019 subjects who underwent detailed baseline examinations in 1991 and a follow-up interview in 2002. Each subject was assigned model-based estimates of average PM10 during the 12 months preceding each health assessment and the difference was used as the exposure variable of interest (DeltaPM10). Analyses were stratified by symptom status at baseline and associations between DeltaPM10 and change in symptom status during follow-up were adjusted for important baseline characteristics, smoking status at follow-up, and season. We then estimated adjusted odds ratios for symptoms at follow-up and numbers of symptomatic cases prevented due to the observed reductions in PM10.Residential exposure to PM10 was lower in 2002 than in 1991 (mean decline 6.2 microg/m3; SD = 3.9 microg/m3). Estimated benefits (per 10,000 persons) attributable to the observed changes in PM10-levels were: 259 (95% confidence interval [CI]: 102-416) fewer subjects with regular cough, 179 (95% CI, 30-328) fewer subjects with chronic cough or phlegm and 137 (95% CI, 9-266) fewer subjects with wheezing and breathlessness.Reductions in particle levels in Switzerland over the 11-year follow-up period had a beneficial effect on respiratory symptoms among adults.
Diuresis or urinary alkalinisation for salicylate poisoning?
Authors: L F Prescott, M Balali-Mood, J A Critchley, A F Johnstone, A T Proudfoot
Journal: BMJ (1982)

Forty-four adults with aspirin poisoning were treated with oral fluids only, standard forced alkaline diuresis, forced diuresis alone, or sodium bicarbonate (alkali) alone. Alkali alone was at least as effective and possibly more effective than forced alkaline diuresis in enhancing salicylate removal. Unlike the diuresis regimens it did not cause fluid retention or biochemical disturbances. The renal excretion of salicylate depends much more on urine pH than flow rate, and forced diuresis alone had little useful effect. In overdosage aspirin causes sodium and fluid retention and may impair renal function. Attempts to force a diuresis are potentially hazardous and the spurious fall in plasma salicylate concentration caused by haemodilution gives a false impression of efficacy. Further studies are required to determine the optimum treatment for salicylate poisoning.
Cardiac Performance in Experimental Adrenal Insufficiency in Cats
Authors: ALLAN M. LEFER, RICHARD L. VERRIER, WALTER W. CARSON
Journal: Circulation Research (1968)

Cardiac function was evaluated by ventricular function curves during the cardiovascular collapse observed in acute and chronic adrenal insufficiency. A progressive decline in peak cardiac work was observed in the acutely adrenalectomized cat (30% decrease at 1.8 hours and 50% at 3.5 hours after adrenalectomy). This impairment in cardiac work paralleled the decrease in mean arterial blood pressure which reached 50 mm Hg 3.5 hours after adrenalectomy. Cortisol and d -aldosterone, and the volume-expander, dextran, prevented a significant fall in mean arterial blood pressure and in peak cardiac work. When the mean arterial blood pressure of nonadrenalectomized cats was adjusted to follow the changes seen in adrenalectomized cats, a 49% depression in cardiac work resulted 3.5 hours after the initial decline in arterial blood pressure. The data suggest that the time course of the hypotension and presumed reduction in coronary perfusion pressure is sufficient to account for the large impairment in peak cardiac work observed. Cardiac work was reduced 56% in chronically adrenalectomized cats 8 to 10 days after adrenalectomy. Dexamethasone and deoxycorticosterone acetate, administered separately, prevented significant myocardial impairment. Since the mean arterial blood pressure of conscious, chronically adrenalectomized cats was normal, the myocardial depression was not secondary to inadequate coronary perfusion in chronic adrenal insufficiency and thus represents direct impairment of myocardial performance.
Acute Blood Pressure Effects and Chronic Hypotensive Action of Calcimimetics in Uremic Rats
Authors: Tobias Odenwald, Kumiko Nakagawa, Charlotte Hadtstein, Frank Roesch, Peter Gohlke, Eberhard Ritz, Franz Schaefer, Claus Peter Schmitt
Journal: Journal of the American Society of Nephrology (2006)

A previous study in subtotally nephrectomized (SNX) rats suggested beneficial effects of the calcimimetic R-568 beyond the control of mineral metabolism. This study analyzed potential blood pressure (BP)-lowering effects of R-568. Male Sprague-Dawley rats received two-stage subtotal nephrectomy or sham operation. Telemetry devices were inserted into the abdominal aorta, and BP was measured every 5 min. R-568 (20 mg/kg per d) or solvent was infused for 4 wk followed by once-daily subcutaneous injections for 2 wk. Total body sodium was measured by neutron activation analysis. The uremia-induced increase of mean arterial pressure from baseline to day 42 in SNX solvent rats (103+/-5 to 128+/-14 mmHg, P=0.006) was attenuated by R-568 (104+/-5 to 111+/-8 mmHg; P<0.0001 for difference of slopes). The circadian rhythm was abrogated in SNX rats and not restored by R-568. In sham-operated rats, R-568 had only a minor transient antihypertensive effect. R-568 injection induced a transient rise of mean arterial pressure by 23+/-4 and 26+/-10 mmHg in sham and SNX rats but only by 9+/-3 and 10+/-5 mmHg in solvent-treated rats (P<0.01 versus baseline and solvent versus R-568). Plasma angiotensin-converting enzyme activity and aldosterone levels were similar; food intake and physical activity did not differ throughout the study. In healthy rats, total body sodium was higher after 14 d of R-568 compared with solvent infusion (37.1+/-4 versus 32.5+/-1.4 mmol/kg; P=0.01). The calcimimetic R-568 causes an initial BP increase in sham-operated and uremic rats, which in uremic rats is followed by a marked and sustained antihypertensive effect.
The Impact of Salsalate Treatment on Serum Levels of Advanced Glycation End Products in Type 2 Diabetes
Authors: Joshua I. Barzilay, Kathleen A. Jablonski, Vivian Fonseca, Steven E. Shoelson, Allison B. Goldfine, Christopher Strauch, Vincent M. Monnier
Journal: Diabetes Care (2013)

OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine [measured as furosine]) and AGE levels (glyoxal and methylglyoxal hydroimidazolones [G-(1)H, MG-(1)H], carboxymethyllysine [CML], carboxyethyllysine [CEL], pentosidine) were measured in patient serum samples. RESULTS Forty-eight weeks of salsalate treatment lowered levels of HbA1c and serum furosine (P < 0.001) and CML compared with placebo. The AGEs CEL and G-(1)H and MG-(1)H levels were unchanged, whereas pentosidine levels increased more than twofold (P < 0.001). Among salsalate users, increases in adiponectin levels were associated with lower HbA1c levels during follow-up (P < 0.001). Changes in renal and inflammation factor levels were not associated with changes in levels of early or late glycation factors. Pentosidine level changes were unrelated to changes in levels of renal function, inflammation, or cytokines. CONCLUSIONS Salsalate therapy was associated with a reduction in early but not late glycation end products. There was a paradoxical increase in serum pentosidine levels suggestive of an increase in oxidative stress or decreased clearance of pentosidine precursor.
Major NHS survey finds care standards are improving but medication information is poor
Authors: A. O'Dowd
Journal: BMJ (2010)

The NHS is showing marked improvements in cleanliness and in reducing mixed sex accommodation, a survey published this week has found.

Patients gave a mixed but overwhelmingly positive review of the health service in the Survey of adult inpatients 2009 , published by NHS regulator the Care Quality Commission. However, a few problems persisted.

The survey of NHS hospital inpatients in 162 hospital trusts in England was carried out between September 2009 and January 2010. Views were gathered from 69 000 patients who were discharged from hospital before the end of August 2009.

Results indicated that improvements have been made in cleanliness and mixed sex accommodation is in decline, but more action is needed …
Spatiotemporal Transition to Conduction Block in Canine Ventricle
Authors: Jeffrey J. Fox, Mark L. Riccio, Fei Hua, Eberhard Bodenschatz, Robert F. Gilmour
Journal: Circulation Research (2002)

Interruption of periodic wave propagation by the nucleation and subsequent disintegration of spiral waves is thought to mediate the transition from normal sinus rhythm to ventricular fibrillation. This sequence of events may be precipitated by a period doubling bifurcation, manifest as a beat-to-beat alternation, or alternans, of cardiac action potential duration and conduction velocity. How alternans causes the local conduction block required for initiation of spiral wave reentry remains unclear, however. In the present study, a mechanism for conduction block was derived from experimental studies in linear strands of cardiac tissue and from computer simulations in ionic and coupled maps models of homogeneous one-dimensional fibers. In both the experiments and the computer models, rapid periodic pacing induced marked spatiotemporal heterogeneity of cellular electrical properties, culminating in paroxysmal conduction block. These behaviors resulted from a nonuniform distribution of action potential duration alternans, secondary to alternans of conduction velocity. This link between period doubling bifurcations of cellular electrical properties and conduction block may provide a generic mechanism for the onset of tachycardia and fibrillation.
Emergency Medical Services and Highway Safety
Authors: William Haddon
Journal: JAMA (1980)

To the Editor.—  The MEDICAL NEWS article, A Capsule History of US Emergency Medical Care (1980;243:1019), contains major errors of omission and commission. First, the National Highway Safety Act of 1966, signed by President Johnson in September of that year, did not just authorize funding of emergency medical services and projects; it also directed the agency, which became the present National Highway Traffic Safety Administration, to issue standards for state highway safety programs that were specifically to include one for emergency services. The National Academy of Sciences study, Accidental Death and Disability: The Neglected Disease of Modern Society , was actually published many weeks after the act was passed, by which time initial discussions were already being held between the then National Highway Safety Bureau and representatives of the governors of all 50 states. These discussions resulted in the appointment by mid-1967 by each governor of a coordinator, whose job
Obtaining tissue from the mediastinum: endoscopic ultrasound guided transoesophageal biopsy
Authors: Roberts Sa
Journal: Thorax (2000)

Endoluminal or endoscopic ultrasound (EUS) was first attempted in 1957 by Wild and Reid who placed a mechanical ultrasound transducer in the rectum.1 It was not until 1975 that the upper gastrointestinal tract was examined when Rasmussen et al 2 measured the stomach wall thickness with a 6 MHz transducer passed through the biopsy channel of a gastroscope. In the 1980s, with the development of a dedicated endoscope incorporating a mechanical ultrasound transducer, EUS became important in clinical practice. Accurate local and nodal staging of oesophageal, gastric, and pancreatic tumours3-6 and assessment of stone disease in the biliary tract7 established EUS in the investigation of gastrointestinal disease. The accurate detection of mediastinal lymph nodes in oesophageal cancer had obvious implications for patients with lung cancer, and the role of EUS in lung cancer was first described in Japan in 1988.8 Further work confirmed the superior accuracy of EUS in the nodal staging of lung cancer compared with computed tomographic (CT) scanning,9 although EUS is not yet used routinely in the preoperative staging of lung cancer in the UK.

Further technical advancement led to the development of the linear EUS probe. This allows passage of a needle down the biopsy channel of the endoscope, through the wall of the gastrointestinal tract, and into adjacent structures such as lymph nodes. The orientation of the ultrasound beam, parallel rather than perpendicular to the long axis of the endoscope, allows continuous ultrasound monitoring of the …
Lifetime Prevalence of Mental Disorders in Lebanon: First Onset, Treatment, and Exposure to War
Authors: Elie G Karam, Zeina N Mneimneh, Hani Dimassi, John A Fayyad, Aimee N Karam, Soumana C Nasser, Somnath Chatterji, Ronald C Kessler
Journal: PLoS Medicine (2008)

There are no published data on national lifetime prevalence and treatment of mental disorders in the Arab region. Furthermore, the effect of war on first onset of disorders has not been addressed previously on a national level, especially in the Arab region. Thus, the current study aims at investigating the lifetime prevalence, treatment, age of onset of mental disorders, and their relationship to war in Lebanon.The Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation study was carried out on a nationally representative sample of the Lebanese population (n = 2,857 adults). Respondents were interviewed using the fully structured WHO Composite International Diagnostic Interview 3.0. Lifetime prevalence of any Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder was 25.8%. Anxiety (16.7%) and mood (12.6%) were more common than impulse control (4.4%) and substance (2.2%) disorders. Only a minority of people with any mental disorder ever received professional treatment, with substantial delays (6 to 28 y) between the onset of disorders and onset of treatment. War exposure increased the risk of first onset of anxiety (odds ratio [OR] 5.92, 95% confidence interval [CI] 2.5-14.1), mood (OR 3.32, 95% CI 2.0-5.6), and impulse control disorders (OR 12.72, 95% CI 4.5-35.7).About one-fourth of the sample (25.8%) met criteria for at least one of the DSM-IV disorders at some point in their lives. There is a substantial unmet need for early identification and treatment. Exposure to war events increases the odds of first onset of mental disorders.
The Appropriateness of Hysterectomy
Authors: Steven J. Bernstein
Journal: JAMA (1993)

<h3>Objective.</h3> —To develop and test a method for comparing the appropriateness of hysterectomy use in different health plans. <h3>Design.</h3> —Retrospective cohort study. <h3>Setting.</h3> —Seven managed care organizations. <h3>Patients.</h3> —Random sample of all nonemergency, nononcological hysterectomies performed in the seven managed care organizations over a 1-year period. Patients who were not continuously enrolled in a plan for 2 years prior to their hysterectomy were excluded. <h3>Main Outcome Measures.</h3> —Proportion of women undergoing hysterectomy in each plan for inappropriate clinical reasons according to ratings derived from a panel of managed care physicians. <h3>Results.</h3> —Overall, about 16% of women underwent hysterectomy for reasons judged to be clinically inappropriate. Only one plan had significantly more hysterectomies rated inappropriate compared with the group mean (27%, unadjusted). Adjusting for age and race did not affect the rankings of the plans and had little effect on the numeric results. <h3>Conclusion.</h3> —The rates of inappropriate use of hysterectomies are similar to those for other procedures and vary to a small degree among health plans. This information may be useful to purchasers when they consider which health plans to offer their employees. (<i>JAMA</i>. 1993;269:2398-2402)
IL-17A Stimulates the Progression of Giant Cell Tumors of Bone
Authors: Meng Xu, Zhi-Gang Song, Cheng-Xiong Xu, Guang-Hua Rong, Ke-Xing Fan, Ji-Ying Chen, Wei Zhang, Jin-Peng Jia, Gang Han, Wei Wang, Wei Chai, Wen-Tao Liang, Wen-Zhi Bi, Yan Wang
Journal: Clinical Cancer Research (2013)

Giant cell tumors of bone (GCTB) exhibit aggressive bone lytic behavior. Studies have shown that interleukin 17A (IL-17A) is involved pathologic bone resorption in various skeletal disorders. Thus, we have investigated the role of IL-17A in GCTBs.We evaluated the progression of GCTBs using Campanacci grading and Enneking staging systems in 74 patients with GCTB. The expression of IL-17A and the IL-17A receptor A (IL-17RA) was assessed in GCTB tissues and in both multinucleated giant cells (MNGC) and stromal cells cultured in vitro using immunostaining and reverse transcription PCR (RT-PCR). The effects of IL-17A on the osteolytic activity of the MNGCs and the proliferation of the stromal cells were investigated using the "pit" formation and MTT assays, respectively. The effects of IL-17A on the expression of proosteolytic factors were examined in primary cultured MNGCs and stromal cells using RT-PCR, Western blotting, and gene expression microarrays.In GCTBs, we detected abundant levels of IL-17A, which were associated with tumor extension and grade. IL-17A is predominantly produced by MNGCs, whereas IL-17RA is expressed by both MNGCs and stromal cells in GCTBs. In the MNGCs, the IL-17A increased the mRNA expression of IL-17A and proosteolytic enzymes, and also enhanced osteolytic ability. In the stromal cells, the IL-17A stimulated cellular proliferation and the expression of proosteolytic factors, including RANKL through myc and STAT3, respectively. In addition, IL-17A stimulated in vivo tumor growth and the extent of angiogenesis in GCTBs.IL-17A stimulates the progression of GCTBs and might represent a useful candidate marker for progression and as a therapeutic target for GCTBs.
Linkage between IgE receptor–mediated histamine releasability from basophils and gene marker of chromosome 11q13
Authors: Yoon-Keun Kim, Sang-Heon Cho, Young-Yull Koh, Jee-Woong Son, Byung-Jae Lee, Kyung-Up Min, You-Young Kim
Journal: Journal of Allergy and Clinical Immunology (1999)
Matrix metalloproteinase genes on chromosome 11q22 and the risk of anterior cruciate ligament (ACL) rupture
Authors: M Posthumus, M Collins, L Van Der Merwe, D O'Cuinneagain, W Van Der Merwe, W J Ribbans, M P Schwellnus, S M Raleigh
Journal: British Journal of Sports Medicine (2011)

Background Anterior cruciate ligament (ACL) rupture is a complex disorder for which several risk factors, including genetic factors, have been established. Objective As matrix metalloproteinases (MMPs) are critical to ligament homeostasis and integrity, the primary aim of this study was to investigate if four selected polymorphisms within four MMP genes, which cluster on chromosome 11q22, associate with risk of ACL ruptures. Methods 343 (138 individuals with ACL ruptures (ACL group) and 215 asymptomatic controls (CON group)) unrelated Caucasians were recruited for this case-control genetic association study. The ACL group included 54 participants with a non-contact mechanism of ACL rupture (NON- subgroup). All participants were genotyped using fluorescence-based assays, for the four selected functional polymorphisms; namely the MMP10 C/T rs486055, MMP1 1G/2G rs1799750, MMP3 G/A rs679620 and MMP12 A/G rs2276109 variants. Results When adjusted for sex, age and weight, the AG and GG genotypes of the MMP12 rs2276109 variant were significantly (p=0.030) under-represented among the NON-subgroups (14%), when compared to the CON group (26%). No other variants were significantly different between groups. In addition, when adjusted for the same confounders, the four variant haplotypes T-1G-A-A (CON 14%, ACL 9%, p=0.033) and C-2G-G-G (CON 14%, NON 5%, p=0.021) were significantly different between the CON group and the ACL group, as well as the CON and NON sub-group, respectively. Conclusion This study reports for the first time that the chromosomal region 11q22 is associated with risk of ACL rupture. The genetic risk profile reported in this study, together with genetic risk factors previously associated, and those yet to be identified, should in the future be included in multifactorial models designed to reduce the incidence of ACL rupture within ‘at-risk’ populations. Further research is required to replicate these findings in an independent population.