tbuckley/cabot-search huggingface dataset:
Maximum rate of change in oesophageal pressure assessed from unoccluded breaths: an option where mouth occlusion pressure is impractical
Authors: CH Hamnegard, MI Polkey, D Kyroussis, GH Mills, M Green, B Bake, J Moxham
Journal: European Respiratory Journal (1998)

The mouth occlusion pressure 100 ms after onset of inspiration (P0.1) is considered a clinically useful measure of the combined output of the respiratory centre and muscle pump. However, theoretical and practical difficulties can arise when using P0.1 in the assessment of patients with severe chronic obstructive pulmonary disease (COPD). It was hypothesized that the maximum rate of change in oesophageal pressure (dPoes,max/dt) may be an alternative to P0.1. To test this hypothesis P0.1 was compared with mean dPoes,max/dt measured from neighbouring unoccluded breaths in five normal subjects during CO2 rebreathing. In all subjects a close correlation was found between both dPoes,max/dt and P0.1 and carbon dioxide tension (PCO2). In six patients with severe COPD performing exhaustive treadmill walks, dPoes,max/dt was found to increase progressively with walking time. Mean dPoes,max/dt at the start was 6.2 cmH2O x 100 ms(-1) and at the finish was 18.7 cmH2O x 100 ms(-1) (p&lt;0.03). In conclusion, the maximum rate of change in oesophageal pressure measured from unoccluded breaths could be an alternative in circumstances where it is not feasible to use measurements of the mouth occlusion pressure 100 ms after onset of inspiration.
Mechanisms Underlying Erythrocyte and Endothelial Nitrite Reduction to Nitric Oxide in Hypoxia
Authors: Andrew J. Webb, Alexandra B. Milsom, Krishnaraj S. Rathod, Wai Lum Chu, Shehla Qureshi, Matthew J. Lovell, Florence M.J. Lecomte, David Perrett, Carmelo Raimondo, Espeed Khoshbin, Zubair Ahmed, Rakesh Uppal, Nigel Benjamin, Adrian J. Hobbs, Amrita Ahluwalia
Journal: Circulation Research (2008)

Reduction of nitrite (NO(2)(-)) provides a major source of nitric oxide (NO) in the circulation, especially in hypoxemic conditions. Our previous studies suggest that xanthine oxidoreductase (XOR) is an important nitrite reductase in the heart and kidney. Herein, we have demonstrated that conversion of nitrite to NO by blood vessels and RBCs was enhanced in the presence of the XOR substrate xanthine (10 micromol/L) and attenuated by the XOR inhibitor allopurinol (100 micromol/L) in acidic and hypoxic conditions only. Whereas endothelial nitric oxide synthase (eNOS) inhibition had no effect on vascular nitrite reductase activity, in RBCs L-NAME, L-NMMA, and L-arginine inhibited nitrite-derived NO production by >50% (P<0.01) at pH 7.4 and 6.8 under hypoxic conditions. Western blot and immunohistochemical analysis of RBC membranes confirmed the presence of eNOS and abundant XOR on whole RBCs. Thus, XOR and eNOS are ideally situated on the membranes of RBCs and blood vessels to generate intravascular vasodilator NO from nitrite during ischemic episodes. In addition to the proposed role of deoxyhemoglobin, our findings suggest that the nitrite reductase activity within the circulation, under hypoxic conditions (at physiological pH), is mediated by eNOS; however, as acidosis develops, a substantial role for XOR becomes evident.
A new 2-regression model for the Actical accelerometer
Authors: S E Crouter, D R Bassett
Journal: British Journal of Sports Medicine (2007)

Objective: The objective of this study was to develop a new 2-regression model relating Actical activity counts to METs. Methods: Forty-eight participants (mean (SD) age 35 (11.4) years) performed 10 min bouts of various activities ranging from sedentary behaviours to vigorous physical activities. Eighteen activities were split into three routines with each routine being performed by 20 individuals. Forty-five routines were randomly selected for the development of a new 2-regression model and 15 tests were used to cross-validate the new 2-regression model and compare it against existing equations. During each routine, the participant wore an Actical accelerometer on the hip and oxygen consumption was simultaneously measured by a portable metabolic system. The coefficient of variation (CV) of four consecutive 15 s epochs was calculated for each minute. For each activity, the average CV and the counts min −1 were calculated for minutes 4–9. If the CV was ⩽13% a walk/run regression equation was used and if the CV was &gt;13% a lifestyle/leisure time physical activity regression was used. Results: An exponential regression line (R 2 = 0.912; standard error of the estimate (SEE) = 0.149) was used for activities with a CV⩽13%, and a cubic regression line (R 2 = 0.884, SEE = 0.804) was used for activities with a CV&gt;13%. In the cross-validation group the mean estimates, using the new 2-regression model with an inactivity threshold, were within 0.56 METs of measured METs for each of the activities performed (p⩾0.05), except cycling (p&lt;0.05). Conclusion: For most activities examined the new 2-regression model predicted METs more accurately than currently available equations for the Actical accelerometer.
Massachusetts health reform and disparities in joint replacement use: difference in differences study
Authors: A. D. Hanchate, A. Kapoor, J. N. Katz, D. McCormick, K. E. Lasser, C. Feng, M. G. Manze, N. R. Kressin
Journal: BMJ (2015)

<b>Objective</b> To estimate the impact of the insurance expansion in 2006 on use of knee and hip replacement procedures by race/ethnicity, area income, and the use of hospitals that predominantly serve poor people ("safety net hospitals"). <b>Design</b> Quasi-experimental difference in differences study examining change after reform in the share of procedures performed in safety net hospitals by race/ethnicity and area income, with adjustment for patients' residence, demographics, and comorbidity. <b>Setting</b> State of Massachusetts, United States. <b>Participants</b> Massachusetts residents aged 40-64 as the target beneficiaries of reform and similarly aged residents of New Jersey, New York, and Pennsylvania as the comparison (control) population. <b>Main outcomes measures</b> Number of knee and hip replacement procedures per 10 000 population and use of safety net hospitals. Procedure counts from state discharge data for 2.5 years before and after reform, and multivariate difference in differences. Poisson regression was used to adjust for demographics, economic conditions, secular time, and geographic factors to estimate the change in procedure rate associated with health reform by race/ethnicity and area income. <b>Results</b> Before reform, the number of procedures (/10 000) in Massachusetts was lower among Hispanic people (12.9, P&lt;0.001) than black people (28.1) and white people (30.1). Overall, procedure use increased 22.4% during the 2.5 years after insurance expansion; reform in Massachusetts was associated with a 4.7% increase. The increase associated with reform was significantly higher among Hispanic people (37.9%, P&lt;0.001) and black people (11.4%, P&lt;0.05) than among white people (2.8%). Lower income was not associated with larger increases in procedure use. The share of knee and hip replacement procedures performed in safety net hospitals in Massachusetts decreased by 1.0% from a level of 12.7% before reform. The reduction was larger among Hispanic people (−6.4%, P&lt;0.001) than white people (−1.0%), and among low income residents (−3.9%, p&lt;0.001) than high income residents (0%). <b>Conclusions</b> Insurance expansion can help reduce disparities by race/ethnicity but not by income in access to elective surgical care and could shift some elective surgical care away from safety net hospitals.
Phase III Trial Comparing Supportive Care Alone With Supportive Care With Oral Topotecan in Patients With Relapsed Small-Cell Lung Cancer
Authors: Mary E.R. O'Brien, Tudor-Eliade Ciuleanu, Hristo Tsekov, Yaroslav Shparyk, Branka Čučeviá, Gabor Juhasz, Nicholas Thatcher, Graham A. Ross, Graham C. Dane, Theresa Crofts
Journal: Journal of Clinical Oncology (2006)

Purpose For patients with small-cell lung cancer (SCLC), further chemotherapy is routinely considered at relapse after first-line therapy. However, proof of clinical benefit has not been documented. Patients and Methods This study randomly assigned patients with relapsed SCLC not considered as candidates for standard intravenous therapy to best supportive care (BSC) alone (n = 70) or oral topotecan (2.3 mg/m 2 /d, days 1 through 5, every 21 days) plus BSC (topotecan; n = 71). Results In the intent-to-treat population, survival (primary end point) was prolonged in the topotecan group (log-rank P = .0104). Median survival with BSC was 13.9 weeks (95% CI, 11.1 to 18.6) and with topotecan, 25.9 weeks (95% CI, 18.3 to 31.6). Statistical significance for survival was maintained in a subgroup of patients with a short treatment-free interval (≤ 60 days). Response to topotecan was 7% partial and 44% stable disease. Patients on topotecan had slower quality of life deterioration and greater symptom control. Principal toxicities with topotecan were hematological: grade 4 neutropenia, 33%; grade 4 thrombocytopenia, 7%; and grade 3/4 anemia, 25%. Comparing topotecan with BSC, infection ≥ grade 2 was 14% versus 12% and sepsis 4% versus 1%; other grade 3/4 events included vomiting 3% versus 0, diarrhea 6% versus 0, dyspnea 3% versus 9%, and pain 3% versus 6%. Toxic deaths occurred in four patients (6%) in the topotecan arm. All cause mortality within 30 days of random assignment was 13% on BSC and 7% on topotecan. Conclusion Chemotherapy with oral topotecan is associated with prolongation of survival and quality of life benefit in patients with relapsed SCLC.
Extracellular Matrix Promotes Highly Efficient Cardiac Differentiation of Human Pluripotent Stem Cells
Authors: Jianhua Zhang, Matthew Klos, Gisela F. Wilson, Amanda M. Herman, Xiaojun Lian, Kunil K. Raval, Matthew R. Barron, Luqia Hou, Andrew G. Soerens, Junying Yu, Sean P. Palecek, Gary E. Lyons, James A. Thomson, Todd J. Herron, José Jalife, Timothy J. Kamp
Journal: Circulation Research (2012)

Cardiomyocytes (CMs) differentiated from human pluripotent stem cells (PSCs) are increasingly being used for cardiovascular research, including disease modeling, and hold promise for clinical applications. Current cardiac differentiation protocols exhibit variable success across different PSC lines and are primarily based on the application of growth factors. However, extracellular matrix is also fundamentally involved in cardiac development from the earliest morphogenetic events, such as gastrulation.We sought to develop a more effective protocol for cardiac differentiation of human PSCs by using extracellular matrix in combination with growth factors known to promote cardiogenesis.PSCs were cultured as monolayers on Matrigel, an extracellular matrix preparation, and subsequently overlayed with Matrigel. The matrix sandwich promoted an epithelial-to-mesenchymal transition as in gastrulation with the generation of N-cadherin-positive mesenchymal cells. Combining the matrix sandwich with sequential application of growth factors (Activin A, bone morphogenetic protein 4, and basic fibroblast growth factor) generated CMs with high purity (up to 98%) and yield (up to 11 CMs/input PSC) from multiple PSC lines. The resulting CMs progressively matured over 30 days in culture based on myofilament expression pattern and mitotic activity. Action potentials typical of embryonic nodal, atrial, and ventricular CMs were observed, and monolayers of electrically coupled CMs modeled cardiac tissue and basic arrhythmia mechanisms.Dynamic extracellular matrix application promoted epithelial-mesenchymal transition of human PSCs and complemented growth factor signaling to enable robust cardiac differentiation.
The future of colorectal cancer: implications of screening
Authors: Maarten Neerincx, Tineke E Buffart, Chris J J Mulder, Gerrit A Meijer, Henk M W Verheul
Journal: Gut (2013)

In 2003 the countries of the EU agreed to start screening for colorectal cancer (CRC). Currently, several EU countries have implemented a screening programme. As the result of the detection of prevalent cancers with a biannual faecal immunochemical test (FIT) accompanied by an aging population and an increased risk of developing CRC, the incidence of CRC will rise with 35% by 2020 in the Netherlands.1 ,2 Implementation of a screening programme will lead to a more favourable prognosis at diagnosis through the detection of CRC at an early, asymptomatic stage. Of all cancers detected with a single guaiac faecal occult blood test (GFOBT) or FIT, 64–71% will be at stage I or II, compared with 45–60% in matched non-invited symptomatic populations, with FIT showing superiority over GFOBT.3 ,4 The introduction of CRC screening will detect on average 1600 additional stage I and II CRCs per year in the first few years after its introduction in the Netherlands.4 ,5 Interval cancers will still be diagnosed in between screening rounds because not all cancers will be detected when asymptomatic.6 The stage distribution of these interval cancers will mimic those diagnosed in a symptomatic non-screened population.3 ,7 When taking these interval cancers into account, computational models reveal an increase in the proportion of CRCs diagnosed at stages I and II from 53% to 80% without and with annual FIT screening, respectively. Accordingly, a decrease in the proportion of CRCs diagnosed at stages III or IV from 47% to 20% with screening has been predicted. Identical shifts in stage distribution have been observed for all investigated screening strategies.8 Although there might be a selection bias towards an unfavourable stage distribution in the anticipated 40% of the invited population not attending CRC screening, preliminary studies …
Characterization of p53 and p21 Functional Interactions in Glioma Cells en Route to Apoptosis
Authors: C. Gomez-Manzano, J. Fueyo, A. P. Kyritsis, P. A. Steck, V. A. Levin, W. K. Alfred Yung, T. J. McDonnell
Journal: JNCI Journal of the National Cancer Institute (1997)

Alterations of the p53 (also called TP53) gene are one of the most common abnormalities in gliomas. We have previously reported that restoration of wild-type p53 protein function in glioma cells results in programmed cell death (apoptosis). Since p53 functions are mediated by genes that directly control the tumor suppressor effect of the p53 protein, understanding the relationship between p53 and p53-related genes in glioma cells will aid in the design of more rational treatment strategies for brain tumors.We conducted this study to examine the timing of the p53-mediated events preceding apoptosis. More specifically, we undertook this work to characterize the genetic and cell cycle-related factors that may increase the resistance of glioma cells to p53-induced apoptosis.Two human glioma cell lines (U-251 MG and U-373 MG) that express mutant p53 protein and two (U-87 MG and EFC-2) that express wild-type p53 protein were used. Replication-deficient adenovirus was utilized as an expression vector to transfer exogenous p53 and p21 complementary DNAs into the glioma cells; control cells were infected with the viral expression vector alone. To monitor gene transfer and the expression of exogenous genes (as well as the expression of endogenous genes), we used western blot analyses and immunohistochemistry analyses. Flow cytometry studies of cellular DNA content were performed to determine the cell cycle phenotype of the glioma cells before and after treatment.p53-mediated apoptosis was preceded by elevation in the levels of the p21 (cell cycle-related) and Bax (apoptosis-related) proteins. In addition, cell cycle analyses showed that glioma cells were arrested in the G2 phase before undergoing cell death. Transfer of p21 induced a G2 block but did not induce apoptosis. Moreover, coexpression of p21 and p53 prevented glioma cells from undergoing apoptosis. Expression of exogenous p53 in wild-type p53 cells did not induce elevation of Bax levels, arrest in G2 phase, or apoptosis.Our data confirmed the ability of wild-type p53 to induce apoptosis in p53 mutant glioma cells. In addition, our results document that p21 plays a role in protecting cells from p53-mediated programmed cell death and suggest that p53-mediated apoptosis and p21 induction may represent, at least in certain cases, opposite signals. Finally, our data suggest that over expression of p21 in gliomas may be related to resistance to treatments that induce apoptosis.
Extralymphatic involvement in diffuse non-Hodgkin's lymphoma.
Authors: S Paryani, R T Hoppe, J S Burke, P Sneed, D Dawley, R S Cox, S A Rosenberg, H S Kaplan
Journal: Journal of Clinical Oncology (1983)

Between 1961 and 1982, 543 patients with diffuse histiocytic, mixed, or undifferentiated lymphoma were treated at Stanford University, Stanford, Calif. Of this group, 281 (52%) had extralymphatic lesions and the 111 patients with stage IE and IIE disease were subjected to analysis. Most patients (94) had diffuse histiocytic lymphoma. Lymphangiography was performed in 77%, bone marrow biopsy in 91%, and diagnostic or staging laparotomy in 52% of the patients. All but five patients were treated with megavoltage irradiation and 35 patients received combination chemotherapy. Median follow-up was 4.0 years. Kaplan-Meier actuarial survival at five and 10 years was 46% and 36%, respectively. Freedom from relapse (FFR) at five years was 49% with no relapses beyond that point. The most common extralymphatic sites were the gastrointestinal tract, the head and neck region, and the lung. Prognosis could not be correlated with the specific sites of involvement. Patients with bulky disease (greater than 10 cm) or more than three sites of involvement had a significantly lower survival and FFR. There was no significant difference in outcome for patients treated with irradiation or combined modality therapy. Most patients (62%) relapsed in distant extralymphatic sites.
Transforming growth factor beta 1 and interleukin 4 induced alpha smooth muscle actin expression and myofibroblast-like differentiation in human synovial fibroblasts in vitro: modulation by basic fibroblast growth factor
Authors: D L Mattey, P T Dawes, N B Nixon, H Slater
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To discover if α smooth muscle actin expression and myofibroblastic differentiation are induced in synovial fibroblasts by cytokines found in the inflamed RA joint. <h3>METHODS</h3> Immunofluorescent microscopy and western blotting were used to examine different cultures of human synovial fibroblasts for expression of α actin in the presence of the cytokines transforming growth factor β (TGFβ1), interleukin 1α (IL1α), IL4, IL6, tumour necrosis factor α (TNFα), and basic fibroblast growth factor (FGF). <h3>RESULTS</h3> A small but significant population of cells (14.4 ± 12.9%) expressed α actin under standard culture conditions. Upon treatment with TGFβ1 there was a pronounced increase in the number of cells expressing α actin (68.1 ± 5.49%), accompanied by a change in morphology to a myofibroblast-like phenotype. Other cytokines found within the inflamed joint such as IL1, TNFα , IL6, and basic FGF failed to induce α actin expression. However, IL4, which is normally absent or only present at low concentrations in the RA joint had a similar effect to TGFβ1. It was also found that basic FGF inhibited the induction of α actin expression by TGFβ1 and IL4. <h3>CONCLUSION</h3> In the presence of TGFβ1 or IL4, fibroblasts derived from synovial tissue or synovial fluid are induced to differentiate into myofibroblast-like cells containing the α smooth muscle form of actin. This differentiation is inhibited by basic FGF. It is suggested that the balance between these particular cytokines may be important in the modulation of fibroblast behaviour, which could have significant effects on joint repair mechanisms and the generation of fibrous tissue within the rheumatoid joint.
Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in
Authors: T. Kontiokari
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with <i>Lactobacillus</i> GG drink. <b>Design:</b> Open, randomised controlled 12 month follow up trial. <b>Setting:</b> Health centres for university students and staff of university hospital. <b>Participants:</b> 150 women with urinary tract infection caused by <i>Escherichia coli</i> randomly allocated into three groups. <b>Interventions:</b> 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. <b>Main outcome measure:</b> First recurrence of symptomatic urinary tract infection, defined as bacterial growth ≥10<sup>5</sup> colony forming units/ml in a clean voided midstream urine specimen. <b>Results:</b> The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34). <b>Conclusion:</b> Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection. <h3>What is already known on this topic</h3> Up to 60% of women will have a urinary tract infection and a third of them will have several recurrences Vaccinium berries and products containing lactobacilli may affect the coliform bacteria that cause urinary tract infection <h3>What this study adds</h3> 50 ml of cranberry-lingonberry juice concentrate daily reduced recurrences of symptomatic urinary tract infection by about half compared with the control group <i>Lactobacillus</i> GG drink had no effect on recurrence Self treatment with cranberry juice may reduce the need for antimicrobials for recurrent urinary tract infection
Functional relationship between obesity and male reproduction: from humans to animal models
Authors: K. J. Teerds, D. G. de Rooij, J. Keijer
Journal: Human Reproduction Update (2011)

The increase in the incidence of obesity has a substantial societal health impact. Contrasting reports have been published on whether overweight and obesity affect male fertility. To clarify this, we have reviewed published data on the relation between overweight/obesity, semen parameters, endocrine status and human male fertility. Subsequently, we have used results obtained in animal models of obesity to explain the human data. Pubmed, Scopus, Web of Science and Google Scholar databases were searched between September 2009 and October 2010 for a comprehensive publication record. Available studies on adult human males were examined. The included animal studies examined obesity and fertility, and focused on leptin, leptin receptor signaling, kisspeptins and/or NPY. Most overweight/obese men do not experience significant fertility problems, despite the presence of reduced testosterone alongside normal gonadotrophin levels. Only a subgroup of subjects suffers from hypogonadotropic hypogonadism. Animal models offer several explanations and show that reduced leptin signaling leads to reduced GnRH neuronal activity. This may be due to decreased hypothalamic Kiss1 expression, a potent regulator of GnRH/LH/FSH release. As the Kiss1 neurons express leptin receptors, the Kiss1 system may participate in transmitting metabolic information to the GnRH neurons, thus providing a bridge between metabolic regulation and fertility. Infertility in overweight/obese males may be explained by leptin insensitivity. This implies a possible role for the KISS1 system in human obesity-related male infertility. If substantiated, it will pave the way for methods to restore fertility in these subjects.