tbuckley/cabot-search huggingface dataset:
The impact of knee and hip chondrocalcinosis on disability in older people: the ProVA Study from northeastern Italy
Authors: E. Musacchio, R. Ramonda, E. Perissinotto, L. Sartori, R. Hirsch, L. Punzi, S. Zambon, M. C. Corti, G. Baggio, E. Manzato, A. Doria, G. Crepaldi
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Chondrocalcinosis is frequently associated with osteoarthritis. The role of osteoarthritis in the onset and progression of disability is well known. The impact of chondrocalcinosis on disability has never been investigated in epidemiological studies. <h3>Methods</h3> Progetto Veneto Anziani is a survey of 3099 older Italians, focusing on chronic diseases and disability. Assessment was by questionnaires, physical performance tests and clinical evaluations. Chondrocalcinosis was determined by x-ray readings of 1629 consecutive subjects. Knee and hip osteoarthritis severity was evaluated by summing the radiographic features score (RFS) assigned during x-ray reading. <h3>Results</h3> Subjects with chondrocalcinosis were older and more frequently women (age-adjusted p&lt;0.0001). The gender association disappeared following adjustment for osteoarthritis severity. However, at the knee, the prevalence of osteoarthritis was higher in chondrocalcinosis patients independently of age and sex (age-adjusted p&lt;0.0001). No difference was found between chondrocalcinosis and controls in sociodemographic variables and comorbidity. Knee chondrocalcinosis was strongly associated with clinical features of knee osteoarthritis and with disability assessment parameters in the bivariate analysis. Most associations remained after adjusting for age. After further adjustment for RFS, a significant association remained for knee deformity and pain, the need for a cane, difficulty walking 500 m, using a toilet, shopping and repeatedly rising from a chair. <h3>Conclusions</h3> Pain and physical function are the outcome measures of choice for assessing disability in osteoarthritis patients. The presence of chondrocalcinosis contributes to both, independently of age and osteoarthritis severity, thus compromising the quality of life and worsening comorbidity.
Intracoronary Adenovirus-Mediated Delivery and Overexpression of the β <sub>2</sub> -Adrenergic Receptor in the Heart
Authors: Ashish S. Shah, R. Eric Lilly, Alan P. Kypson, Oliver Tai, Jonathan A. Hata, Anne Pippen, Scott C. Silvestry, Robert J. Lefkowitz, Donald D. Glower, Walter J. Koch
Journal: Circulation (2000)

Background —Genetic modulation of ventricular function may offer a novel therapeutic strategy for patients with congestive heart failure. Myocardial overexpression of β 2 -adrenergic receptors (β 2 ARs) has been shown to enhance contractility in transgenic mice and reverse signaling abnormalities found in failing cardiomyocytes in culture. In this study, we sought to determine the feasibility and in vivo consequences of delivering an adenovirus containing the human β 2 AR cDNA to ventricular myocardium via catheter-mediated subselective intracoronary delivery. Methods and Results —Rabbits underwent percutaneous subselective catheterization of either the left or right coronary artery and infusion of adenoviral vectors containing either a marker transgene (Adeno-βGal) or the β 2 AR (Adeno-β 2 AR). Ventricular function was assessed before catheterization and 3 to 6 days after gene delivery. Both left circumflex– and right coronary artery–mediated delivery of Adeno-β 2 AR resulted in ≈10-fold overexpression in a chamber-specific manner. Delivery of Adeno-βGal did not alter in vivo left ventricular (LV) systolic function, whereas overexpression of β 2 ARs in the LV improved global LV contractility, as measured by dP/dt max , at baseline and in response to isoproterenol at both 3 and 6 days after gene delivery. Conclusions —Percutaneous adenovirus-mediated intracoronary delivery of a potentially therapeutic transgene is feasible, and acute global LV function can be enhanced by LV-specific overexpression of the β 2 AR. Thus, genetic modulation to enhance the function of the heart may represent a novel therapeutic strategy for congestive heart failure and can be viewed as molecular ventricular assistance.
Matrix Metalloproteinase 3 Polymorphism
Authors: Hélène Blons, Sophie Gad, Franck Zinzindohoué, Isabelle Manière, Janie Beauregard, David Tregouet, Daniel Brasnu, Philippe Beaune, Ollivier Laccourreye, Pierre Laurent-Puig
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Treatment of head and neck cancer often associates different therapeutic modalities, including surgery, radiotherapy, and chemotherapy. In an attempt to optimize therapeutics, the identification of molecular markers linked to response to chemotherapy remains important. Recently, the involvement of metalloproteinases in resistance to chemotherapy was suggested through their interaction with the Fas/Fas ligand pathway. Indeed metalloproteinases enhance Fas ligand shedding modulating chemotherapy efficiency. On the basis of these findings, we tested the existence of a correlation between response to chemotherapy and four metalloproteinase polymorphisms in a prospective series of 148 head and neck cancer patients. Experimental Design: Patients were genotyped using automated fragment analysis and 5′-nuclease allelic discrimination assay. Response to chemotherapy was clinically assessed without knowledge of the genotype status. Results: A significant relation between the metalloproteinase type 3 (MMP3) −1612insA polymorphism and response to chemotherapy was identified. Indeed, patients with the 6A/6A genotype responded more frequently (86%) to treatment as compared with patients with the 5A/6A (65%) or 5A/5A (55%) genotypes (P = 0.04). A multivariate analysis, including tumor stage, gender, TP53 mutations, and MMP3 polymorphism, showed that the 6A/6A genotype was an independent factor of response to 5-fluorouracil-cisplatin chemotherapy in head and neck cancer patients with an odds ratio of 6.7 as compared with the 5A/5A genotype. Conclusions: This work showed that genotyping the MMP3 gene enhancer polymorphism −1612insA could help predict chemosensitivity in head and neck cancer patients.
Continuous respiratory support in quadriplegic children by bilateral phrenic nerve stimulation.
Authors: H Garrido, J Mazaira, P Gutierrez, E Gonzalez, J Rivas, J Madrazo
Journal: Thorax (1987)

Three children, aged 6-10 years, in whom cervical cord injury at the C1-C2 level resulted in apnoea had bilateral implantation of diaphragm pacemakers. With periods of gradual conditioning of the diaphragm muscle to low frequency stimulation and slow respiratory rates they adapted to continuous ventilatory support by simultaneous stimulation of both hemidiaphragms without evidence of fatigue, so far for periods of 23-47 months.
A multidisciplinary selection model for youth soccer: the Ghent Youth Soccer Project
Authors: R Vaeyens, R M Malina, M Janssens, B Van Renterghem, J Bourgois, J Vrijens, R M Philippaerts
Journal: British Journal of Sports Medicine (2006)

Objectives: To determine the relationships between physical and performance characteristics and level of skill in youth soccer players aged 12–16 years. Methods: Anthropometry, maturity status, functional and sport-specific parameters were assessed in elite, sub-elite, and non-elite youth players in four age groups: U13 (n = 117), U14 (n = 136), U15 (n = 138) and U16 (n = 99). Results: Multivariate analyses of covariance by age group with maturity status as the covariate showed that elite players scored better than the non-elite players on strength, flexibility, speed, aerobic endurance, anaerobic capacity and several technical skills (p&lt;0.05). Stepwise discriminant analyses showed that running speed and technical skills were the most important characteristics in U13 and U14 players, while cardiorespiratory endurance was more important in U15 and U16 players. The results suggest that discriminating characteristics change with competitive age levels. Conclusions: Characteristics that discriminate youth soccer players vary by age group. Talent identification models should thus be dynamic and provide opportunities for changing parameters in a long-term developmental context.
Correlations between findings at computed tomography (CT) and at thoracoscopy/thoracotomy/autopsy in pleural mesothelioma
Authors: P Maasilta, T Vehmas, L Kivisaari, L Tammilehto, K Mattson
Journal: European Respiratory Journal (1991)

Thirty five computed tomography (CT) scans of the thorax and upper abdomen of thirty three patients with malignant pleural mesothelioma were correlated with the findings at thoracotomy (28 patients), thoracoscopy (2 patients) or autopsy (5 patients). Pleural thickening with contrast medium enhancement was detected on the CT scans of all patients. This finding was a valuable diagnostic tool, especially in cases of large amounts of pleural effusion and/or only thin layers of tumour barely or not at all visible on plain film chest X-rays. Difficulties in defining the exact extent of the diseases for clinical staging and/or evaluation of treatment response arose at the following sites: diaphragmatic pleura, chest wall, pericardium, mediastinum and mediastinal lymph nodes. Extension into the lung was difficult to identify following chemo- and/or radiotherapy. Our results show that CT is essential in the clinical management of mesothelioma. We recommend that CT scans of the chest and upper abdomen, using contrast medium enhancement, should be required in routine practice and in particular in clinical trials involving pleural mesothelioma.
Evidence-based approach to revising the SCAT2: introducing the SCAT3
Authors: Kevin M Guskiewicz, Johna Register-Mihalik, Paul McCrory, Michael McCrea, Karen Johnston, Michael Makdissi, Jiří Dvořák, Gavin Davis, Willem Meeuwisse
Journal: British Journal of Sports Medicine (2013)

The Sport Concussion Assessment Tool 2 (SCAT2), which evolved from the 2008 Concussion in Sport Group (CISG) Consensus meeting, has been widely used internationally for the past 4 years. Although the instrument is considered very practical and moderately effective for use by clinicians who manage concussion, the utility and sensitivity of a 100-point scoring system for the SCAT2 has been questioned. The 2012 CISG Consensus Meeting provided an opportunity for several of the world's leading concussion researchers and clinicians to present data and to share experiences using the SCAT2. The purpose of this report is to consider recommendations by the CISG, and to review the current literature to identify the most sensitive and reliable concussion assessment components for inclusion in a revised version—the SCAT3. Through this process, it was determined that important clinical information can be ascertained in a streamlined manner through the use of a multimodal instrument such as the SCAT3. This test battery should include an initial assessment of injury severity using the Glasgow Coma Scale, immediately followed by observing and documenting concussion signs. Once this is complete, symptom endorsement and symptom severity, neurocognitive function and balance function should be assessed in any athlete suspected of sustaining a concussion. There is no evidence to support the use of a composite/total score; however, there is good evidence to support the use of each component (scored independently) in a revised assessment tool.
Oscillating positive expiratory pressure (oPEP) therapy in chronic obstructive pulmonary disease and bronchiectasis
Authors: S. Svenningsen, G. Paulin, A. Wheatley, D. Pike, J. Suggett, D. McCormack, G. Parraga
Journal: European Respiratory Journal (2014)

RATIONALE:  Airway clearance methods such as oscillating positive expiratory pressure (oPEP) are proposed to provide benefit in patients with chronic obstructive pulmonary disease (COPD) and bronchiectasis by mobilizing secretions and enhancing mucous movement.   METHODS:  A six-week cross-over study was completed in 29 subjects (n=15 COPD, n=14 bronchiectasis) who provided written informed consent and were randomized to oPEP therapy (Aerobika®, Trudell Medical International) four-times daily. Pulmonary function tests, the Six Minute Walk distance (6MWD), St George9s Respiratory Questionnaire (SGRQ) and the Patient Evaluation Questionnaire (PEQ) were used to evaluate therapy effects.   RESULTS:  There were no adverse events related to oPEP use. There were statistically significant improvements in 6MWD (p=0.01), SGRQ total score (p=0.01), and the PEQ Cough Frequency (p=0.006), dyspnea (p=0.03) and ease in bringing up sputum (p   CONCLUSIONS:  In subjects with COPD and bronchiectasis, three weeks of oPEP therapy (Aerobika®) was well-tolerated and there was improved dyspnea, quality of life, exercise capacity and ease in bringing up sputum.
Nicotinic Acid Adenine Dinucleotide Phosphate
Authors: JINGFEI CHENG, AHAD N. K. YUSUFI, MICHAEL A. THOMPSON, EDUARDO N. CHINI, JOSEPH P. GRANDE
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Nicotinic acid adenine dinucleotide phosphate (NAADP), a molecule derived from β-NADP, has been shown to trigger Ca 2+ release from intracellular stores of invertebrate eggs and mammalian cell microsomes. NAADP-induced Ca 2+ release occurs through a mechanism distinct from that of inositol-1,4,5-trisphosphate— or cyclic ADP-ribose—elicited Ca 2+ release. This study investigated whether NAADP can be synthesized in rat kidney. Extracts from glomeruli, mesangial cells, and papilla have high NAADP synthetic capacities. Conversely, synthesis of NAADP in kidney cortex was almost undetectable. Furthermore, 9- cis -retinoic acid significantly up-regulated NAADP synthesis in mesangial cells. Authenticity of NAADP biosynthesis in glomeruli was affirmed by HPLC analysis. NAADP stimulated Ca 2+ release from mesangial cell microsomes through a pathway distinct from that of inositol-1,4,5-trisphosphate or cyclic ADP-ribose. NAADP-triggered Ca 2+ release may play an important role in regulation of renal function.
Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial
Authors: Melvin D Lobo, Paul A Sobotka, Alice Stanton, John R Cockcroft, Neil Sulke, Eamon Dolan, Markus van der Giet, Joachim Hoyer, Stephen S Furniss, John P Foran, Adam Witkowski, Andrzej Januszewicz, Danny Schoors, Konstantinos Tsioufis, Benno J Rensing, Benjamin Scott, G André Ng, Christian Ott, Roland E Schmieder
Journal: The Lancet (2015)
Discontinuation of Anticytomegalovirus Therapy in Patients With HIV Infection and Cytomegalovirus Retinitis
Authors: Scott M. Whitcup
Journal: JAMA (1999)

ContextPersons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision.ObjectiveTo determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load.DesignProspective nonrandomized interventional trial performed from July 1997 to August 1999.SettingClinical Center of the National Institutes of Health, Bethesda, Md.PatientsFourteen patients with stable CMV retinitis and HIV infection and CD4+ cell counts higher than 0.15 × 109/L and being treated with systemic anti-CMV medications and HAART.InterventionsDiscontinuation of specific anti-CMV therapy.Main Outcome MeasuresReactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function, quality of life, morbidity, and mortality.ResultsTwelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications. Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (&gt;3 lines) vision loss in 3 patients.ConclusionsMaintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4+ cell counts and who were taking HAART. The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression.
Prolonged Pressor Effects of Selective Stimulation of the Stellate Ganglion
Authors: WAYNE G. ROHSE, MICHAEL KAYE, WALTER C. RANDALL
Journal: Circulation Research (1957)

With both intensity and duration of individual current pulses maintained constant and at low values, frequencies were varied from ½ to 80/sec., and the stimulating current was applied to the stellate ganglion of the open chest dog. Whereas systolic and pulse pressures increased rapidly with the application of high frequency currents, the pressures were not long maintained even though the stimulation was continuous. With low frequency currents, systolic and pulse pressures rose more slowly but to higher levels which were sustained for periods of 5 to 11 hours. It is believed that neither cardiac acceleration nor systemic vasoconstriction contributed significantly to the pressor responses, but rather that augmentation of myocardial contraction and increased systolic ejection were the important causative factors.
Relation of synovitis to knee pain using contrast-enhanced MRIs
Authors: K. Baker, A. Grainger, J. Niu, M. Clancy, A. Guermazi, M. Crema, L. Hughes, J. Buckwalter, A. Wooley, M. Nevitt, D. T. Felson
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> It has been suggested that synovitis causes joint pain. On non-contrast-enhanced MRIs synovial thickening cannot be assessed and on these images synovitis has been inconsistently associated with pain. <h3>Objective</h3> To assess synovial thickening in relation to knee pain severity among subjects in the Multicenter Osteoarthritis Study (MOST) using contrast-enhanced (CE) MRI. <h3>Methods</h3> MOST is a cohort study of people who have, or are at high risk of, knee <i>osteoarthritis</i> (OA). An unselected subset of 535 participants who volunteered underwent CE 1.5 T MRI of one knee. Synovitis was scored in six compartments and a summary score was created. Knee pain severity was assessed using the maximum item score on the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain scale. The association between synovitis and pain severity was examined using a logistic regression model adjusting for age, sex, body mass index (BMI), MRI bone marrow lesions and effusions in the whole sample and in a subgroup without radiographic OA. <h3>Results</h3> 454 of the 535 subjects undergoing CE MRI had complete data on synovitis and WOMAC pain. Mean age was 59 years, mean BMI 30 and 48% were women. In knees with moderate pain, 80% had synovitis. For knee pain, synovitis conferred a 9.2-fold increased odds compared with those without synovitis. In knees without radiographic OA (n=329), there was also an association of synovitis with an increased prevalence of pain. <h3>Conclusion</h3> Synovitis has a strong relation with knee pain severity, an association detected more clearly with CE MRI than suggested by previous studies using non-CE MRI measures of synovitis.
The Effect of Repeated Administration of Cyclophosphamide on Cytochrome P450 2B in Rats
Authors: Parvaneh Afsharian, Ylva Terelius, Zuzana Hassan, Christina Nilsson, Stefan Lundgren, Moustapha Hassan
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The prodrug cyclophosphamide (CPA) is activated by cytochrome P450 (CYP) enzymes. CPA is one of the corner stones in all cancer treatment. We have studied the effect of repeated doses of CPA given at different time intervals on the mRNA, protein levels, and enzyme activity of CYPs in rats. Experimental Design: Two groups of animals (A-75 and A-150) were treated with four doses of CPA (75 and 150 mg/kg, respectively) at short time intervals (6 h). The third group of animals (B-150) was treated with 150 mg/kg at 24-h intervals. Three animals were killed 30 min after administration, and three animals immediately before the next dose. Results: CYP2B1 and CYP2B2 mRNAs were significantly induced at 6 h after each dose in group A-75 (maximum of 2100-fold and 60-fold after the third dose, respectively), whereas the mRNA levels measured at 6 h postadministration in group A-150 were 1,490-fold and 36-fold after the second dose. In group B-150, no significant induction of mRNA levels was observed. CYP2B1 and CYP2B2 protein levels also increased with increased mRNAs. Plasma levels of 4-hydroxy-CPA measured at 30 min after dose correlated well with the increase in protein levels. Conclusion: Up-regulation of CYP2B mRNA, with a concomitant increase in protein expression and activity, were observed after repeated administration of low doses of CPA compared with that found using higher doses, possibly due to toxicity counteracting induction. These results may help in designing more effective dosing schedules for CPA.
Clinical and radiographic features of spondylitic hip disease.
Authors: J S Marks, K Hardinge
Journal: Annals of the Rheumatic Diseases (1979)

The clinical and radiographic features of hip disease in 76 patients with definite ankylosing spondylitis have been studied. Symptomatic hip involvement occurred late in the course of the disease, with a mean delay after the onset of 12 years in males and 7 years in females. Patients with disease onset before the age of 20 developed hip symptoms at an earlier stage. Associated diseases included uveitis (13%), colitis (4%). Bilateral concentric loss of hip joint space with a relatively undeformed femoral head was the commonest radiological change (61%). Localised loss of joint space at the upper pole (16%) was associated with femoral head destruction and a greater degree of osteophytosis, suggesting coincidental or secondary osteoarthrosis. Bony ankylosis of the hips (10%) was present only in women, and the absence of osteophytes, cysts, and bone lesions of the iliac crests and ischial rami suggests that it is a distinct radiographic manifestation of female ankylosing spondylitis.
Prion proteins and the gut: une liaison dangereuse?
Authors: A N SHMAKOV
Journal: Gut (2001)

Prion proteins and the gut: une liaison dangereuse?Ever since Gajdusek implicated a "slow virus" in the transmission of Kuru, the oral route of "infection" of spongiform encephalopathies has attracted considerable interest.Transmission studies in transmissible spongiform encephalopathies (TSEs) have currently become an even more important area of study due to the possible transmission of bovine spongiform encephalopathy (BSE) to humans resulting in "new variant" Creutzfeldt-Jakob disease (vCJD).Prusiner's hypothesis that TSEs are caused by small proteinaceous infectious particles "prions" took considerable time to gain widespread recognition among the scientific establishment.The importance of these discoveries was vindicated by awards of Nobel prizes to Gajdusek and more recently to Prusiner.Two forms of prion proteins are recognised-normal host encoded cellular prion protein (PrP c ) and its pathological malfolded isoform (PrP Sc )-which accumulate in the brain in TSEs including vCJD.PrP c is a copper binding glycoprotein attached to the plasma membrane through a glycosyl-phosphatidyl-inositol anchor. 1 2 Although both isoforms are identical in amino acid sequence, they diVer in their secondary structure: PrP Sc is high in sheet content in contrast with the predominantly helical structure of PrP c .Partial resistance to proteolytic degradation, detergent insolubility, and slower turnover rate also characterise the pathological isoform.