tbuckley/cabot-search huggingface dataset:
Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study
Authors: A. Guermazi, F. W. Roemer, D. Hayashi, M. D. Crema, J. Niu, Y. Zhang, M. D. Marra, A. Katur, J. A. Lynch, G. Y. El-Khoury, K. Baker, L. B. Hughes, M. C. Nevitt, D. T. Felson
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI. <h3>Methods</h3> Multicenter Osteoarthritis Study (MOST) is a cohort study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (&lt;2 mm), grade 1 (2–4 mm) and grade 2 (&gt;4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter- and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed. <h3>Results</h3> 400 subjects were included (mean age 58.8±7.0 years, body mass index 29.5±4.9 kg/m<sup>2</sup>, 46% women). For individual sites, intrareader reliability (weighted κ) was 0.67–1.00 for reader 1 and 0.60–1.00 for reader 2. Inter-reader agreement (κ) was 0.67–0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient ( ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively). <h3>Conclusions</h3> A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.
Peroxisome Proliferator–activated Receptor γ–induced T Cell Apoptosis Reduces Survival during Polymicrobial Sepsis
Authors: Martina Victoria Schmidt, Patrick Paulus, Anne-Marie Kuhn, Andreas Weigert, Virginie Morbitzer, Kai Zacharowski, Volkhard A. J. Kempf, Bernhard Brüne, Andreas von Knethen
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Despite intensive research, sepsis displays the most prevalent cause of death on intensive care units. The hallmark of sepsis is an overshooting T-cell death that reduces host defense mechanisms and that is associated with poor patient survival. Previous in vitro studies revealed that the expression of the transcription factor peroxisome proliferator-activated receptor (PPAR) γ was increased in isolated T cells of patients with sepsis.We determined the importance of targeting PPARγ for sepsis treatment and underlying molecular mechanisms for T-cell apoptosis in vivo.To mimic human systemic inflammation and septic conditions, we used a nonlethal endotoxemia and a lethal cecum ligation and puncture polymicrobial sepsis model.PPARγ inhibition in T cells with either the PPARγ antagonist GW9662 or a newly generated T cell-specific PPARγ knockout (Tc-PPARγ(-/-)) mice provided a survival advantage during polymicrobial sepsis in mice, which correlated with abrogated T-cell depletion in both in vivo models. Pathway analysis revealed increased antiapoptotic IL-2 and Bcl-2 expression, and activated prosurvival PI3K/Akt signaling under PPARγ-deficient conditions. In line, neutralizing IL-2 in Tc-PPARγ(-/-) mice resulted in T-cell apoptosis and increased mortality.Our results provide evidence for a pivotal involvement of PPARγ in T-cell depletion by activating two important apoptosis pathways, and subsequently provoking the breakdown of defense mechanisms during systemic inflammation and sepsis.
Prognostic value of serum alpha-fetoprotein in fulminant hepatic failure including patients treated by charcoal haemoperfusion.
Authors: I M Murray-Lyon, A H Orr, B Gazzard, J Kohn, R Williams
Journal: Gut (1976)

Serum alpha-fetoprotein (AFP) levels have been measured sequentially by a radio-immunoassay method in 64 patients with fulminant hepatic failure. In 15 of the 64 patients (23%) AFP levels were raised but in only two did they exceed 500 ng/ml. Of the 23 survivors 11 (48%) had raised AFP levels compared with four of the 41 (9-8%) fatal cases (P less than 0-005). This rise in AFP levels was found early after the development of grade IV coma and constitutes an encouraging prognostic sign at a time when the liver function tests and EEG are unhelpful. A radioimmunoassay must be used if these small but significant rises in plasma concentration are to be detected. Twelve patients survived without showing a rise in plasma AFP at anytime during the illness. The four fatal cases who had raised AFP levels all had serious complications of fulminant hepatic failure. Charcoal haemoperfusion did not seem to increase the survival of AFP negative patients.
AXR is the most useful initial screening tool in determining position of 'retained' patency capsule
Authors: R. Perowne, C. Parker, C. Davison, O. Schulte, S. Athey, R. Cooper, S. Panter
Journal: Gut (2011)

<h3>Introduction</h3> Capsule endoscopy carries a risk of capsule retention. In patients with risk factors for this, patency capsule (PC) is recommended. Patients are screened at 30 h with radiofrequency scanner, if scan positive (PC present) further imaging is required. This practice is to use AXR to determine PC position, then CT if any uncertainty. The use of scout CT has been advocated to identify the presence of PC in scan positive patients, then limited CT if PC is present. Limitations of this are access to and increased demand for CT. The authors propose that AXR remain the most appropriate screening tool to determine PC position and reduce the requirement for CT. <h3>Aims</h3> To determine the frequency with which position of PC could be confidently identified on AXR by 3 consultant radiologists and requirements for CT scan. <h3>Methods</h3> Of 181 PC9s performed, 74 patients scanned positive. 3 consultant radiologists were asked to retrospectively review the 74 AXR9s performed in these patients and grade the position of the PC. Degree of certainty was assessed by the following scoring system: 1=certain in colon, 2=probably in colon, need CT, 3=position uncertain, need CT, 4=probably not in colon, need CT, 5=definitely not in colon. <h3>Results</h3> In an average of 55% of cases, the radiologist could report with certainty that the PC was in the colon, negating the need for CT. Of these, all but two patients went on to successful video capsule endoscopy (VCE); one patient retained VCE (no CT done), two patient VCE was not done (other reasons). In one patient PC was confidently located in the small bowel; and the patient had successful VCE. In 45% of cases the radiologist was not confident of PC position and recommended CT. This was a retrospective study, therefore discrepancies exist between study recommendations and actual events. <h3>Conclusion</h3> A radiologist can confidently locate the PC on AXR in 55% cases. This data suggests that only 45% of scan positive patients will require CT to identify the location of PC after AXR. This has a beneficial impact in reduction of demand for CT and less radiation exposure for patients. The authors believe an AXR remains a useful and reliable initial screening tool in determining the position of PC in scan positive patients and would recommend its use over scout CT.
IDENTIFICATION OF BIOMARKERS FOR EARLY TENDON DEGENERATION USING AN IN-VIVO RABBIT MODEL
Authors: E Huisman, G Thornton, C Roberts, A Scott
Journal: British Journal of Sports Medicine (2013)

Introduction Tendinopathy is a common and costly diagnosis in workers with Activity-related Soft Tissue Disorder (ASTD), and in recreational and professional athletes. The associated pain results in reduced physical activity, reduced productivity, missed work days, and substantial costs to the government. Workers whose tendons are exposed to prolonged repetitive activity (eg, manual workers like fish processors) and/or high mechanical loads (eg, construction workers) are at high risk for the development of ASTD-associated tendinopathy. Pain is usually one of the first symptoms of tendinopathy; however imaging studies have demonstrated that significant degenerative tendon alterations can develop in response to mechanical loading, months before there are any overt symptoms. Goal: To identify circulation markers of early tendon degeneration. Research questions: (1) Will fatigue damage in tendons, caused by different loading regimes, correlate with changes in expression of genes involved in tendon degeneration? (2) Can we track the development of early phase tendon degeneration in vivo using ultrasound and measure indicators of tendon degradative activity in the circulation? It is hypothesised that different loading regimes will lead to characteristic, degradative differences in gene expression. Ultrasound will be able to visualise and follow early onset, degradative changes in the strained tendons. Methods Rabbit Achilles tendons will be subjected to varying loading regimens using the in-vivo Backman model. After set periods of exercise, microdialysis and blood samples will be taken and analysed for genes involved in degradation of tendons. At the same intervals, ultrasound images will be taken to track changes in the cross sectional area of the tendon. After the end of the full exercise period, the tendon tissue will be examined for characteristic degradative changes using microscopy. Results It is expected that the exercise regimen will lead to significant changes in gene expression in the tendon.1 Blood and microdialysis samples are expected to show significant changes in for example, collagen type I and III, matrix metalloproteinases (MMPs), tissue inhibitors for MMPs (TIMPs), and other genes involved.2 It is expected that the tissue will exhibit characteristic morphological changes seen in degradative tendon tissue, for example, rounded nuclei of tenocytes and a looser, kinked pattern of the collagen fibrils.3 Discussion Treatment for tendinopathies in workers can be a long and costly process which is not always successful, due to the degenerative nature of chronic tendinopathy. Detecting the early stages of tendinopathy could allow for the possibility of interventions to decrease or prevent tendon pain and/or rupture, and reduce healthcare and insurance costs.
Vascular Permeability Factor/Vascular Endothelial Growth Factor Induces Lymphangiogenesis as well as Angiogenesis
Authors: Janice A. Nagy, Eliza Vasile, Dian Feng, Christian Sundberg, Lawrence F. Brown, Michael J. Detmar, Joel A. Lawitts, Laura Benjamin, Xiaolian Tan, Eleanor J. Manseau, Ann M. Dvorak, Harold F. Dvorak
Journal: The Journal of Experimental Medicine (2002)

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A(164), we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A-expressing tumors. We now report that, in addition to inducing angiogenesis, VEGF-A(164) also induces a strong lymphangiogenic response. This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D. The new "giant" lymphatics generated by VEGF-A(164) were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas/lymphatic malformations, perhaps implicating VEGF-A in the pathogenesis of these lesions. Whereas the angiogenic response was maintained only as long as VEGF-A was expressed, giant lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation.
Influence of Small-Group Education Sessions on Glucose Homeostasis in NIDDM
Authors: Itamar Raz, Varda Soskolne, Pnina Stein
Journal: Diabetes Care (1988)

In patients with non-insulin-dependent diabetes mellitus (NIDDM), the influence of knowledge about their disease on the treatment and control of the disease is not clear. We evaluated the efficacy of educational group meetings with NIDDM patients on improving their knowledge of the disease and on disease management. Fifty-one NIDDM patients were randomly assigned to either intervention or control groups. The intervention group participated in courses of three weekly lessons presented by a physician, nurse, and dietitian once every 4 mo. The intervention and control groups were also followed once every 2 mo in the clinic by the same staff. Medical treatment remained unchanged during the study. After a 12-mo follow-up of the intervention group, no significant improvement in their knowledge of diabetes could be demonstrated. However, mean fasting and postprandial blood glucose levels and HbA1c improved significantly in comparison with the control goup. The same tendency was evident with the weight and lipoprotein profile. We conclude that educational group therapy can improve diabetes control in patients with NIDDM.
Heat shock proteins: the missing link between hormonal and reproductive factors and rheumatoid arthritis?
Authors: J A da Silva
Journal: Annals of the Rheumatic Diseases (1991)

Epidemiologic data suggest a strong link between hormonal and reproductive factors and the incidence of rheumatoid arthritis. Of interest is a possible protective effect of oral contraceptives or estrogen replacement therapy against the development of rheumatoid arthritis. At least 1 pregnancy also appears to reduce the risk of this disease. It has been hypothesized that hormonal contraceptive use and pregnancy elicit the production of higher amounts of endogenous heat shock proteins, which, in turn, induce immunotolerance to subsequent exposure to the actual triggering agent of rheumatoid arthritis. A related possibility is that pregnant women are exposed to specific types of heat shock proteins produced by the fetus in high concentrations. Heat shock proteins are known to be the predominant antigens related to the induction of reactive arthritis. The production of some such proteins is dependent on sex hormones in a tissue-specific way and their concentrations are raised dramatically by stimulation with estrogen and progesterone. A possible mechanism for heat protein-induced immunotolerance would be the predominant stimulation of a suppressor T cell clone. More research on the pathogenesis of rheumatic diseases and the activity of sex hormones could result in the development of a vaccine against rheumatoid arthritis.
Transvenous lung biopsy in the pig.
Authors: M Hakim, P G Stovin, T A English, J Wallwork
Journal: Thorax (1986)

At present there is no satisfactory technique for repeated lung biopsy in recipients of heart-lung transplants. A new technique for lung biopsy, which might be adopted for this purpose, has been developed. A Teflon sheath is inserted through the jugular vein into the pulmonary artery with the aid of a balloon catheter. A flexible biopsy forceps is then introduced through the sheath into the pulmonary arterial tree and advanced into the periphery of the lung, where biopsy samples are taken. The procedure was attempted in 14 pigs. Initially crocodile jaw (two pigs) and fenestrated cups forceps (five pigs), which are currently in use for transbronchial lung biopsy, were used. Subsequently the biopsy forceps was modified and the jaws were replaced by a cutting needle mechanism (six pigs). Out of the 13 animals in which the procedure was technically possible, lung parenchyma was obtained from nine and pulmonary arterial wall from 11. One animal died shortly after the procedure. The cause of death could not be determined with certainty at postmortem examination. There was, however, a small tear on the surface of the lung, which could have produced a tension pneumothorax. The other 12 animals recovered from the procedure. They were killed 24 hours later and postmortem examination was carried out. One animal in which the crocodile jaw forceps had been used had a haematoma in the lower lobe (3 X 3 X 4 cm) and 100 ml of blood in the pleural cavity. In the other 11 animals, in which the fenestrated cups or the cutting needle forceps had been used, the intrapulmonary haematomas were 1-2 cm in diameter and the pleural surface was intact. It is concluded therefore that transvenous lung biopsy is feasible and that this procedure might find an application in monitoring rejection in recipients of heart-lung transplants.
Suicide Risk During Antidepressant Treatment
Authors: Gregory E Simon, James Savarino, Belinda Operskalski, Philip S Wang
Journal: American Journal of Psychiatry (2006)

In March 2004 the U.S. Food and Drug Administration (FDA) warned physicians and patients regarding increased risk of suicide with 10 newer antidepressant drugs. Available data leave considerable uncertainty regarding actual risk of suicide attempt and death by suicide during antidepressant treatment. The authors used population-based data to evaluate the risk of suicide death and serious suicide attempt in relation to initiation of antidepressant treatment.Computerized health plan records were used to identify 65,103 patients with 82,285 episodes of antidepressant treatment between Jan. 1, 1992, and June 30, 2003. Death by suicide was identified by using state and national death certificate data. Serious suicide attempt (suicide attempt leading to hospitalization) was identified by using hospital discharge data.In the 6 months after the index prescription of antidepressant treatment, 31 suicide deaths (40 per 100,000 treatment episodes) and 76 serious suicide attempts (93 per 100,000) were identified in the study group. The risk of suicide attempt was 314 per 100,000 in children and adolescents, compared to 78 per 100,000 in adults. The risk of death by suicide was not significantly higher in the month after starting medication than in subsequent months. The risk of suicide attempt was highest in the month before starting antidepressant treatment and declined progressively after starting medication. When the 10 newer antidepressants included in the FDA advisory were compared to older drugs, an increase in risk after starting treatment was seen only for the older drugs.The risk of suicide during acute-phase antidepressant treatment is approximately one in 3,000 treatment episodes, and risk of serious suicide attempt is approximately one in 1,000. Available data do not indicate a significant increase in risk of suicide or serious suicide attempt after starting treatment with newer antidepressant drugs.
Mechanism of Vascular Smooth Muscle Relaxation by Estrogen in Depolarized Rat and Mouse Aorta
Authors: Ana D. Freay, Sylvia W. Curtis, Kenneth S. Korach, Gabor M. Rubanyi
Journal: Circulation Research (1997)

Abstract 17β-Estradiol induces vasodilation in vitro and in vivo, which has been suggested to contribute to the cardiovascular protection by this ovarian steroid hormone. However, the exact mechanism of vasorelaxation by estrogens remains to be elucidated. In this study, we analyzed the potential role of genomic mechanisms involving the nuclear estrogen receptor and inhibition of entry of extracellular Ca 2+ in 17β-estradiol–induced vasorelaxation in depolarized aortic rings, isolated from male and female rats and male mice. In both male and female rat aortic rings without endothelium and in intact male mouse aortic rings treated with N G -nitro- l -arginine, 17β-estradiol caused dose-dependent (0.3 to 30 μmol/L) relaxation of contraction evoked by high-K + depolarization (30 and 45 mmol/L KCl, respectively). The estrogen receptor antagonist ICI 164384 had no effect on 17β-estradiol–induced relaxations. 125 I-17β-estradiol binding studies showed the presence of high-affinity cytosolic-nuclear estrogen receptors in control male mouse aortas. Comparable relaxations of aortic rings isolated from control and estrogen receptor–deficient transgenic mice provided direct evidence that the nuclear estrogen receptor is not involved in this response. 17β-Estradiol–induced relaxation of rat aortic rings could not be prevented by cycloheximide or actinomycin D, suggesting that the response was not mediated by de novo protein synthesis or gene transcription. In rat aortic rings, 17β-estradiol inhibited the increase of 45 Ca uptake by 30 mmol/L KCl at concentrations (10 and 30 μmol/L) that caused vasorelaxation in the same tissue, suggesting that inhibition of Ca 2+ entry contributes to the response. 17α-Estradiol was less effective, and estrone was devoid of vasorelaxing activity. Vasorelaxation by estrogens in female and male rat aortas was similar, indicating no gender difference in vascular responses under these conditions.
Siah-1 Interacts with the Intracellular Region of Polycystin-1 and Affects Its Stability via the Ubiquitin-Proteasome Pathway
Authors: Hyunho Kim, Woocho Jeong, Kwangseog Ahn, Curie Ahn, Seongman Kang
Journal: Journal of the American Society of Nephrology (2004)

Autosomal dominant polycystic kidney disease, characterized by extensive formation of renal cysts and progressive renal failure, is a genetic disorder caused by mutations in the PKD1 and PKD2 genes. The PKD1 gene product, polycystin-1, is a transmembrane protein with its N-terminus facing the extracellular region and C-terminus facing the cytoplasm. Polycystin-1 seems to be involved in regulating cell growth and maturation, but the precise mechanisms are not yet well defined. For investigating the function of the intracellular region of polycystin-1, the C-terminal cytoplasmic fragment of polycystin-1, PKD1-C, was used as bait in two-hybrid screening, and a polycystin-1-binding protein, the human homologue of Drosophila Seven in Absentia (Siah-1), which has a RING domain and promotes the ubiquitin-dependent proteasome pathway, was identified. It was shown that PKD1-C interacts with Siah-1 in vivo. In addition, interaction with Siah-1 induces the degradation of PKD1-C, shortening its half-life. PKD1-C and CD4 chimeric proteins, which are attached to the plasma membrane, also show similar results. Furthermore, ubiquitination and degradation of PKD1-C are increased in the presence of Siah-1, and overexpression of Siah-1 protein promotes the degradation of polycystin-1 via the ubiquitin-proteasome pathway. These results suggest that polycystin-1 is regulated by Siah-1 through the ubiquitin-dependent proteasome pathway.
Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial
Authors: Jyh-Ming Liou, Chieh-Chang Chen, Mei-Jyh Chen, Chien-Chuan Chen, Chi-Yang Chang, Yu-Jen Fang, Ji–Yuh Lee, Shih-Jer Hsu, Jiing-Chyuan Luo, Wen-Hsiung Chang, Yao-Chun Hsu, Cheng-Hao Tseng, Ping-Huei Tseng, Hsiu-Po Wang, Ueng-Cheng Yang, Chia-Tung Shun, Jaw-Town Lin, Yi-Chia Lee, Ming-Shiang Wu
Journal: The Lancet (2012)