tbuckley/cabot-search huggingface dataset:
Ca2+ transients in perfused hearts revealed by gated 19F NMR spectroscopy.
Authors: E Marban, M Kitakaze, V P Chacko, M M Pike
Journal: Circulation Research (1988)

Gated acquisition of 19F nuclear magnetic resonance spectra from perfused ferret hearts loaded with the fluorinated Ca2+ indicator 5,5'-F2-BAPTA allows direct quantitation of the cyclical changes in the intracellular free Ca2+ concentration ([Ca2+]i) that underlie contraction in intact hearts. [Ca2+]i increased from approximately 200 nM in diastole to approximately 1 microM or higher in early systole. Although the 19F spectra that report [Ca2+]i changed dramatically and reproducibly during the cardiac cycle, no changes were detectable in gated phosphorus spectra. We exploited the ability to control the coronary arterial flow of our hearts to investigate the mechanism of the fall in contractility that results from a decrease in perfusion even when the flow suffices to sustain normal high energy phosphate concentrations. Under these conditions, the amplitude of Ca2+ transients falls markedly along with the decline in pressure. This down-regulation of Ca2+ transients constitutes a novel protective mechanism that minimizes energy demand during low-flow ischemia.
Inorganic Arsenite-Induced Malignant Transformation of Human Prostate Epithelial Cells
Authors: W. E. Achanzar, E. M. Brambila, B. A. Diwan, M. M. Webber, M. P. Waalkes
Journal: JNCI Journal of the National Cancer Institute (2002)

Although several epidemiologic studies show an association between arsenic exposure and prostate cancer, it is still unknown whether human prostate epithelial cells are directly susceptible to arsenic-induced transformation. This study was designed to determine whether the nontumorigenic human prostate epithelial cell line RWPE-1 could be malignantly transformed in vitro by arsenite. RWPE-1 cells were continuously exposed to 5 micro M arsenite and monitored for signs of transformation, assessed as changes in matrix metalloproteinase-9 levels. After 29 weeks of exposure, the arsenite-exposed RWPE-1 cells (referred to as CAsE-PE) showed a marked increase in matrix metalloproteinase-9 secretion, a common finding in prostate malignancies. Malignant transformation was confirmed when CAsE-PE cells produced aggressive undifferentiated malignant epithelial tumors in nude mice. The tumors stained positive for human prostate-specific antigen, confirming their origin. These results are the first report of arsenite-induced malignant transformation of a human epithelial cell line and provide an important in vitro model for studying the mechanisms underlying arsenic-induced carcinogenesis in humans.
Doppler US with perfusion software and contrast medium injection in the early evaluation of isolated limb perfusion of limb sarcomas: prospective study of 49 cases
Authors: N. Lassau, M. Lamuraglia, D. Vanel, A. Le Cesne, L. Chami, S. Jaziri, P. Terrier, A. Roche, J. Leclere, S. Bonvalot
Journal: Annals of Oncology (2005)
Diurnal Blood Pressure Changes One Year after Kidney Transplantation
Authors: Hani M. Wadei, Hatem Amer, Sandra J. Taler, Fernando G. Cosio, Matthew D. Griffin, Joseph P. Grande, Timothy S. Larson, Thomas R. Schwab, Mark D. Stegall, Stephen C. Textor
Journal: Journal of the American Society of Nephrology (2007)

Loss of circadian BP change has been linked to target organ damage and accelerated kidney function loss in hypertensive patients with and without chronic kidney disease. Ambulatory BP-derived data from 119 consecutive kidney transplant recipients who presented for the first annual evaluation were examined in relation to allograft function, histology, and ultrasound findings. A total of 101 (85%) patients were receiving antihypertensive medications (median 2), and 85 (71%) achieved target awake average systolic BP (SBP) of <135 mmHg. A day-night change in SBP by 10% or more (dippers) was detected in 29 (24%). Dipping status was associated with younger recipient age, lack of diabetes, low chronic vascular score, and low resistive index. Nondippers and reverse dippers had lower GFR compared with dippers (P = 0.04). For every 10% nocturnal drop in SBP, GFR increased by 4.6 ml/min per 1.73 m(2) (R = 0.3, P = 0.003). Nondippers and reverse dippers were equally common in recipients with normal histology and in those with pathologic findings on surveillance biopsy. On multivariate analysis, percentage of nocturnal fall in SBP and elevated resistive index independently correlated with GFR. This study indicates that lack of nocturnal fall in SBP is related to poor allograft function, high chronic vascular score, and high resistive index irrespective of allograft fibrosis. Further studies are needed to determine whether restoration of normal BP pattern will confer better allograft outcome.
Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
Authors: Serge A. Jabbour, Elise Hardy, Jennifer Sugg, Shamik Parikh,
Journal: Diabetes Care (2013)

To assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin.In this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) ± metformin (≥1,500 mg/day).Baseline HbA1c and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA1c levels (-0.5% [-4.9 mmol/mol]) versus placebo (0.0% [+0.4 mmol/mol]). Dapagliflozin reduced body weight versus placebo (-2.1 and -0.3 kg) and reduced HbA1c levels in patients with baseline values ≥8.0% (-0.8% [8.7 mmol/mol] and 0.0% [0.3 mmol/mol]) and fasting plasma glucose levels (-24.1 mg/dL [-1.3 mmol/L] and 3.8 mg/dL [0.2 mmol/L]). Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%).These results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.
Determination of subfractions of amniotic fluid alpha-fetoprotein in diagnosing spina bifida and congenital nephrosis.
Authors: E Ruoslahti, A Pekkala, D E Comings, M Seppala
Journal: BMJ (1979)

46XY.Her basal serum concentration of testosterone was 15 nmol/l (4-33 ng/ml) and rose to 18 nmol/l (5.19 ng/ml) after HCG stimulation.
P261 Analysis of the Prevalence and Predictors of Obesity Hypoventilation Syndrome in a Cohort of Overweight Patients with Suspected Sleep Disordered Breathing
Authors: V Macavei, K Spurling, J Loft, H Makker
Journal: Thorax (2012)

<h3>Introduction</h3> The need for early detection of Obesity Hypoventilation Syndrome (OHS) is clear because delay in the diagnosis and treatment is associated with significant morbidity and mortality. <h3>Objective</h3> To determine the prevalence of obesity hypoventilation syndrome among obese patients with suspected sleep apnoea and determine the validity of previously reported predictors of OHS such as serum bicarbonate level. <h3>Methods</h3> A retrospective analysis of prospectively collected sleep clinic data on 525 consecutive obese patients referred to sleep clinic from January 2009 to January 2011 to a university hospital was performed. Subjects with suspected sleep disordered breathing were evaluated according to our clinical protocol and capillary blood gases were measured in obese (BMI&gt; 30) subjects. <h3>Results</h3> 525 consecutive patients (mean age 51.44±12.7, 65.71% males, mean BMI 34.59±8.1) were evaluated. A total of 344 (65.52%) were obese (mean age 52.29±12.4, 63.66% males) of which 128 (37.2%) were morbidly obese (BMI&gt;40 kg/m<sup>2</sup>). Daytime hypercapnia (paCO<sub>2</sub>&gt;6 kPa) was detected in 20.63% (71/344) obese and 22.1% (61/275) obstructive sleep apnoea (OSA) patients. Univariate analysis of potential predictors of OHS showed significant correlations between paCO<sub>2</sub> and BMI, FEV1, FVC, AHI, mean nocturnal SpO<sub>2</sub>, minimum nocturnal SpO<sub>2</sub>, sleep time spent with SpO<sub>2</sub> &lt;90%, paO<sub>2</sub> and serum HCO<sub>3</sub>. Following stepwise multiple regression, paO<sub>2</sub> and HCO<sub>3</sub> were found to be independent predictors of OHS explaining 27.7% of paCO2 variance (p&lt;0.0001). On logistic regression analysis, serum HCO<sub>3</sub> cut-off of &gt;27 mmol was found to have 85% sensitivity and 90% specificity for diagnosis of OHS. <h3>Conclusion</h3> We confirmed high prevalence of OHS in obese patients with OSA (22.1%) that would be possible to diagnose by measuring serum HCO3 levels, thereby eliminating the need for arterial blood gas sampling.
Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans
Authors: Hashem B. El‐Serag, Eric A. Engels, Ola Landgren, Elizabeth Chiao, Louise Henderson, Harshinie C. Amaratunge, Thomas P. Giordano
Journal: Hepatology (2008)

Hepatitis C virus (HCV) may increase the risk of hepatopancreaticobiliary tumors other than hepatocellular carcinoma (HCC). Previous case control studies indicated a possible association between HCV and intrahepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extrahepatic cholangiocarcinoma (ECC) or pancreatic cancer. We conducted a cohort study including 146,394 HCV-infected and 572,293 HCV-uninfected patients who received care at Veterans Affairs health care facilities. Patients with two visits between 1996 and 2004 with HCV infection were included, as were up to four matched HCV-uninfected subjects for each HCV-infected subject. Risks of ICC, ECC, pancreatic cancer, and HCC were assessed using proportional hazards regression. In the 1.37 million person-years of follow-up, which began 6 months after the baseline visit, there were 75 cases of ECC, 37 cases of ICC, 617 cases of pancreatic cancer, and 1679 cases of HCC. As expected, the risk of HCC associated with HCV was very high (hazard ratio [HR], 15.09; 95% confidence interval [95% CI], 13.44, 16.94). Risk for ICC was elevated with HCV infection 2.55; 1.31, 4.95), but risk for ECC was not significantly increased (1.50; 0.60, 1.85). Adjustments for cirrhosis, diabetes, inflammatory bowel disease, hepatitis B, alcoholism, and alcoholic liver disease did not reduce the risk for ICC below twofold. The risk of pancreatic cancer was slightly elevated (1.23; 1.02, 1.49), but was attenuated after adjusting for alcohol use, pancreatitis, and other variables.Findings indicated that HCV infection conferred a more than twofold elevated risk of ICC. Absence of an association with ECC was consistent in adjusted and unadjusted models. A significant association with pancreatic cancer was erased by alcohol use and other variables.
Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis
Authors: Mária Filková, Borbala Aradi, Ladislav Šenolt, Caroline Ospelt, Serena Vettori, Heřman Mann, Andrew Filer, Karim Raza, Christopher D Buckley, Martyn Snow, Jiří Vencovský, Karel Pavelka, Beat A Michel, Astrid Jüngel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA). <h3>Objective</h3> To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome. <h3>Methods</h3> Total RNA was isolated from whole sera in ERA patients (prior to and after 3 and 12 months of therapy with disease modifying antirheumatic drugs), in patients with established RA and in healthy controls (HC) using phenol–chloroform extraction. Expression of miR-146a, miR-155, miR-223, miR-16, miR-203, miR-132 and miR-124a was analysed by TaqMan Real Time PCR. <h3>Results</h3> From all analysed miRNAs, levels of miR-146a, miR-155 and miR-16 were decreased in the sera of ERA patients in comparison with established RA. A change in circulating miR-16 in the first 3 months of therapy was associated with a decrease in DAS28 in long term follow-up in ERA (p=0.002). Levels of circulating miR-223 in treatment naïve ERA correlated with C reactive protein (p=0.008), DAS28 (p=0.031) and change in DAS28 after 3 months (p=0.003) and 12 months (p=0.011) of follow-up. However, neither miR-16 nor miR-223 could distinguish ERA from HC. <h3>Conclusions</h3> Differential expression of circulating miR-146a, miR-155 and miR-16 in the sera of ERA patients may characterise an early stage of the disease. We suggest miR-223 as a marker of disease activity and miR-16 and miR-223 as possible predictors for disease outcome in ERA.
Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial
Authors: Roman Prymula, Marianne Riise Bergsaker, Susanna Esposito, Leif Gothefors, Sorin Man, Nadezhda Snegova, Mária Štefkovičova, Vytautas Usonis, Jacek Wysocki, Martine Douha, Ventzislav Vassilev, Ouzama Nicholson, Bruce L Innis, Paul Willems
Journal: The Lancet (2014)
Intra-Arterial Urokinase Infusion in Diabetic Patients With Rapidly Progressive Ischemic Foot Lesions
Authors: Pietro Vannini, Adolfo Ciavarella, Anna Mustacchio, Cristina Rossi
Journal: Diabetes Care (1991)

Objective The effectiveness of local intra-arterial thrombolysis by urokinase was evaluated in eight non-insulin-dependent diabetic patients with angiographic evidence of infrapopliteal occlusive disease and rapidly progressive foot lesions. Research Design and Methods With an electric peristaltic pump, urokinase was infused for 96 h by a 5-6 F catheter introduced into the femoral artery and placed immediately above the occluded infrapopliteal arteries. After baseline, angiography was repeated at 24- to 48-h intervals and at conclusion of the treatment. Results Six patients showed immediate improvement of clinical symptoms. Angiography revealed the reestablishment of blood flow in collateral vessels of the leg and foot in the dorsal pedal artery in three patients and in the plantar arch in two. Recanalization of the major arteries of the trifurcation was not achieved. After 12 mo of follow-up, all limbs were salvaged, although four patients required vascular reconstruction to further improve foot perfusion and complete healing. Conclusions Intra-arterial urokinase, which opens collateral and smaller vessels of the leg and foot in patients with diabetes, may be effective in improving blood flow in lower extremities and in making the patient a better candidate for vascular surgery.
Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergy
Authors: Hans Michael Haitchi, David J.P. Bassett, Fabio Bucchieri, Xiufeng Gao, Robert M. Powell, Neil A. Hanley, David I. Wilson, Stephen T. Holgate, Donna E. Davies
Journal: Journal of Allergy and Clinical Immunology (2009)
Randomized, Controlled Trial of Yoga in Women With Breast Cancer Undergoing Radiotherapy
Authors: Kavita D. Chandwani, George Perkins, Hongasandra Ramarao Nagendra, Nelamangala V. Raghuram, Amy Spelman, Raghuram Nagarathna, Kayla Johnson, Adoneca Fortier, Banu Arun, Qi Wei, Clemens Kirschbaum, Robin Haddad, G. Stephen Morris, Janet Scheetz, Alejandro Chaoul, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2014)

Purpose Previous research incorporating yoga (YG) into radiotherapy (XRT) for women with breast cancer finds improved quality of life (QOL). However, shortcomings in this research limit the findings. Patients and Methods Patients with stages 0 to III breast cancer were recruited before starting XRT and were randomly assigned to YG (n = 53) or stretching (ST; n = 56) three times a week for 6 weeks during XRT or waitlist (WL; n = 54) control. Self-report measures of QOL (Medical Outcomes Study 36-item short-form survey; primary outcomes), fatigue, depression, and sleep quality, and five saliva samples per day for 3 consecutive days were collected at baseline, end of treatment, and 1, 3, and 6 months later. Results The YG group had significantly greater increases in physical component scale scores compared with the WL group at 1 and 3 months after XRT (P = .01 and P = .01). At 1, 3, and 6 months, the YG group had greater increases in physical functioning compared with both ST and WL groups (P &lt; .05), with ST and WL differences at only 3 months (P &lt; .02). The group differences were similar for general health reports. By the end of XRT, the YG and ST groups also had a reduction in fatigue (P &lt; .05). There were no group differences for mental health and sleep quality. Cortisol slope was steepest for the YG group compared with the ST and WL groups at the end (P = .023 and P = .008) and 1 month after XRT (P = .05 and P = .04). Conclusion YG improved QOL and physiological changes associated with XRT beyond the benefits of simple ST exercises, and these benefits appear to have long-term durability.
A long-term visual outcome comparison in patients with optic nerve sheath meningioma managed with observation, surgery, radiotherapy, or surgery and radiotherapya aNo author has any commercial interest in any of the opinions expressed in this article.
Authors: Roger E Turbin, Charlotte R Thompson, John S Kennerdell, Kimberly Peele Cockerham, Mark J Kupersmith
Journal: Ophthalmology (2002)
MECHANISM AND CONTROL OF V(D)J RECOMBINATION AT THE IMMUNOGLOBULIN HEAVY CHAIN LOCUS
Authors: David Jung, Cosmas Giallourakis, Raul Mostoslavsky, Frederick W. Alt
Journal: Annual Review of Immunology (2006)

V(D)J recombination assembles antigen receptor variable region genes from component germline variable (V), diversity (D), and joining (J) gene segments. For B cells, such rearrangements lead to the production of immunoglobulin (Ig) proteins composed of heavy and light chains. V(D)J is tightly controlled at the Ig heavy chain locus (IgH) at several different levels, including cell-type specificity, intra- and interlocus ordering, and allelic exclusion. Such controls are mediated at the level of gene segment accessibility to V(D)J recombinase activity. Although much has been learned, many long-standing questions regarding the regulation of IgH locus rearrangements remain to be elucidated. In this review, we summarize advances that have been made in understanding how V(D)J recombination at the IgH locus is controlled and discuss important areas for future investigation.
Switching between TNF inhibitors in psoriatic arthritis: data from the NOR-DMARD study
Authors: Karen Minde Fagerli, Elisabeth Lie, Désirée van der Heijde, Marte Schrumpf Heiberg, Synøve Kalstad, Erik Rødevand, Knut Mikkelsen, Åse Stavland Lexberg, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tumour necrosis factor inhibitors (TNFi) are efficacious in patients with psoriatic arthritis (PsA), but some patients do not respond or do not tolerate their first TNFi, and are switched to a different TNFi. Evidence supporting this practice is limited, and we wanted to investigate the effectiveness of switching to a second TNFi. <h3>Material and methods</h3> From a longitudinal observational study (LOS) we selected patients with PsA who were starting their first TNFi, and identified patients who had switched to a second TNFi ('switchers'). Three-month responses and 3-year drug-survival were compared between switchers and non-switchers, and within switchers. <h3>Results</h3> Switchers (n=95) receiving their second TNFi had significantly poorer responses compared with non-switchers (n=344) (ACR50 response: 22.5% vs 40.0%, DAS28 remission: 28.2% vs 54.1%). There was a trend towards poorer responses to the second TNFi compared with the first TNFi within switchers. Estimated 3-year drug-survival was 36% for the second TNFi compared with 57% for the first TNFi overall. <h3>Conclusions</h3> 20–40% of patients had a response on a second TNFi after having failed one TNFi in this LOS. This observation highlights the need for treatments with other mechanisms of action than TNF inhibition in patients with PsA.
Community Care in England
Authors: Nathaniel M. Hawkins, Shaun Scholes, Madhavi Bajekal, Hande Love, Martin O'Flaherty, Rosalind Raine, Simon Capewell
Journal: Circulation (2012)

Socioeconomic deprivation is associated with increased heart failure (HF) incidence, hospitalization rates, and mortality. However, whether the delivery of survival-enhancing medical therapy is equitable remains uncertain. We examined secular trends in the uptake of key medical therapies (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, spironolactone) stratified by socioeconomic circumstances in patients with HF. Secondary analyses examined trends in HF incidence, prevalence, and survival.This study was a cross-sectional observational analysis of nationally representative primary care data from England. Treatments for patients with HF in 1999 and 2007 (n=13 330) were extracted from the General Practice Research Database. Socioeconomic circumstances were defined with the Index of Multiple Deprivation 2007, a weighted composite of 7 area-level deprivation domains. Treatment uptake estimates were age standardized. The incidence and prevalence of HF decreased year to year. Although clear socioeconomic gradients in both the incidence and prevalence of HF were apparent, the absolute difference between most and least deprived reduced over time. Uptake of therapies improved over time in both men and women. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker uptake increased from 46% to 64%, β-blocker uptake from 12% to 41%, and spironolactone uptake from 3% to 20%. Modest age and sex inequalities were apparent. However, no consistent socioeconomic gradients were observed in either treatment or case fatality.Socioeconomic gradients in the incidence and prevalence of HF are reducing. Treatment is generally equitable and independent of socioeconomic circumstances. Most important, no significant inequality in outcomes was apparent. Future strategies should continue to address inequalities in the underlying causes of HF and to increase overall treatment levels further.