tbuckley/cabot-search huggingface dataset:
Correlation of cytidine deaminase polymorphisms and activity with clinical outcome in gemcitabine-/platinum-treated advanced non-small-cell lung cancer patients
Authors: C. Tibaldi, E. Giovannetti, M. Tiseo, L.G. Leon, A. D'Incecco, N. Loosekoot, M. Bartolotti, R. Honeywell, F. Cappuzzo, A. Ardizzoni, G.J. Peters
Journal: Annals of Oncology (2011)
Long-term results favor allogeneic over autologous hematopoietic stem cell transplantation in patients with refractory or recurrent indolent non-Hodgkin’s lymphoma
Authors: C. Hosing, R.M. Saliba, P. McLaughlin, B. Andersson, M.A. Rodriguez, L. Fayad, F. Cabanillas, R.E. Champlin, I.F. Khouri
Journal: Annals of Oncology (2003)
Studies of the Mechanism by Which Chronic Metabolic Acidosis Augments Urinary Calcium Excretion in Man*
Authors: Jacob Lemann, John R. Litzow, Edward J. Lennon
Journal: Journal of Clinical Investigation (1967)

We carried out clearance studies in nine healthy adults and four patients with hypoparathyroidism before and after inducing stable metabolic acidosis with either NH(4)Cl or acetazolamide. Clearances were repeated in seven normal subjects and three of the patients 3 days after stopping these agents.During acidosis in the normal subjects, serum ultrafilterable calcium concentration rose significantly, but inulin clearance fell to a greater extent, so that the calculated filtered load of calcium fell significantly. Despite this, urinary calcium excretion rose. Urinary calcium excretion remained elevated in the recovery studies when the serum ultrafilterable calcium concentration and filtered load of calcium had returned to control levels. Evidence is presented indicating that the increased calcium excretion which occurred during acidosis and recovery clearances was not due to natriuresis or to increased excretion of complexing anions. The comparable results in the four patients with hypoparathyroidism, two of whom also had hypothyroidism, suggest that the capacity to alter secretion rates of parathyroid hormone, thyrocalcitonin or both is not a critical determinant of the augmented rates of calcium excretion during acidosis.We conclude that metabolic acidosis produces increased urinary calcium excretion by causing decreased renal tubular calcium reabsorption. Evidence is presented which suggests that this is a direct effect of metabolic acidosis on metabolic processes within renal tubular cells.
Vascular Regeneration by Local Growth Factor Release Is Self-Limited by Microvascular Clearance
Authors: Kha N. Le, Chao-Wei Hwang, A. Rami Tzafriri, Mark A. Lovich, Alison Hayward, Elazer R. Edelman
Journal: Circulation (2009)

The challenge of angiogenesis science is that stable sustained vascular regeneration in humans has not been realized despite promising preclinical findings. We hypothesized that angiogenic therapies powerfully self-regulate by dynamically altering tissue characteristics. Induced neocapillaries increase drug clearance and limit tissue retention and subsequent angiogenesis even in the face of sustained delivery.We quantified how capillary flow clears fibroblast growth factor after local epicardial delivery. Fibroblast growth factor spatial loading was significantly reduced with intact coronary perfusion. Penetration and retention decreased with transendothelial permeability, a trend diametrically opposite to intravascular delivery, in which factor delivery depends on vascular leak, but consistent with a continuum model of drug transport in perfused tissues. Model predictions of fibroblast growth factor sensitivity to manipulations of its diffusivity and transendothelial permeability were validated by conjugation to sucrose octasulfate. Induction of neocapillaries adds pharmacokinetic complexity. Sustained local fibroblast growth factor delivery in vivo produced a burst of neovascularization in ischemic myocardium but was followed by drug washout and a 5-fold decrease in fibroblast growth factor penetration depth.The very efficacy of proangiogenic compounds enhances their clearance and abrogates their pharmacological benefit. This self-limiting property of angiogenesis may explain the failures of promising proangiogenic therapies.
Angiotensin II antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice
Authors: K. A. Keogh, J. Standing, G. C. Kane, A. Terzic, A. H. Limper
Journal: European Respiratory Journal (2005)

Based on current evidence, transforming growth factor (TGF)-β plays a central pathogenic role in the development of pulmonary fibrosis. There is growing evidence that angiotensin II can serve as a stimulus for TGF-β-mediated lung fibrosis. However, the role of angiotensin II in the pathobiology of pulmonary fibrosis in vivo remains unclear and the therapeutic potential for targeting angiotensin II in a bleomycin-induced pulmonary fibrosis model is not well known. Therefore, the aim of this study was to test whether the angiotensin II antagonist, losartan, attenuated the development of bleomycin-induced pulmonary fibrosis in two distinct murine strains, C57/BL6 and Sv129. This was determined by histopathology and quantification of collagen content by hydroxyproline assay. Despite demonstrable angiotensin II antagonism in vivo and a reduction in measures of acute lung injury, losartan therapy, at a dose shown to reduce renal and cardiac fibrosis in mice, failed to significantly ameliorate bleomycin-induced pulmonary fibrosis. In conclusion, these data suggest that the pulmonary fibrotic disease process in vivo is not solely dependent on angiotensin II activity and the potential for angiotensin II receptor blockers as a therapeutic strategy in patients with pulmonary fibrosis may be limited.
FDG-PET in T-cell and NK-cell neoplasms
Authors: S. Kako, K. Izutsu, Y. Ota, Y. Minatani, M. Sugaya, T. Momose, K. Ohtomo, Y. Kanda, S. Chiba, T. Motokura, M. Kurokawa
Journal: Annals of Oncology (2007)
Patient Satisfaction and Glycemic Control After 1 Year With Inhaled Insulin (Exubera) in Patients With Type 1 or Type 2 Diabetes
Authors: Julio Rosenstock, Joseph C. Cappelleri, Björn Bolinder, Robert A. Gerber
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to determine patient satisfaction in patients with type 1 or type 2 diabetes receiving an inhaled insulin or subcutaneous insulin regimen, as assessed by pooled analysis of two 12-week parent studies and 1-year extension studies. RESEARCH DESIGN AND METHODS—In the 12-week parent studies, patients with type 1 (n = 70) or type 2 (n = 51) diabetes were randomized to an inhaled insulin or subcutaneous insulin regimen. In the 1-year extension studies, patients were allowed to select either treatment regimen. Patient satisfaction was assessed at baseline, week 12, and 1 year using the Patient Satisfaction with Insulin Therapy questionnaire. RESULTS—Of the 60 patients who received inhaled insulin during the parent studies, 85.0% (n = 51) chose to continue treatment, 13.3% (n = 8) switched to subcutaneous insulin, and 1.7% (n = 1) did not continue. Of the 61 patients who received subcutaneous insulin, 21.3% (n = 13) chose to continue treatment, 75.4% (n = 46) switched to inhaled insulin, and 3.3% (n = 2) did not continue. From baseline (parent studies) to 1 year (extension studies), HbA1c reductions of 0.8% were sustained, and greater improvements were observed in the inhaled insulin group compared with the subcutaneous insulin group in terms of overall satisfaction (37.9 vs. 3.1%; P &amp;lt; 0.01) and ease of use (43.2 vs. −0.9%; P &amp;lt; 0.01). CONCLUSIONS—Inhaled insulin was preferred over subcutaneous insulin, which resulted in greater patient satisfaction up to 1 year in patients with type 1 or type 2 diabetes with durable effects on HbA1c levels.
Polymorphisms in Resistin (RETN) and Resistin-like Beta (RETNLB) and Risk of Asthma in Independent Populations of African Descent
Authors: L. Gao, E. Coe, M. Campbell, M. Yang, T. Hand, N.M. Rafaels, A. Poloczek, H. Watson, G. Dunston, N. Hansel
Journal: Journal of Allergy and Clinical Immunology (2009)
Community-Based Participatory Research From the Margin to the Mainstream
Authors: Carol R. Horowitz, Mimsie Robinson, Sarena Seifer
Journal: Circulation (2009)

Despite an increasing arsenal of effective treatments, there are mounting challenges in developing strategies that prevent and control cardiovascular diseases, and that can be sustained and scaled to meet the needs of those most vulnerable to their impact. Community-based participatory research (CBPR) is an approach to conducting research by equitably partnering researchers and those directly affected by and knowledgeable of the local circumstances that impact health. To inform research design, implementation and dissemination, this approach challenges academic and community partners to invest in team building, share resources, and mutually exchange ideas and expertise. CBPR has led to a deeper understanding of the myriad factors influencing health and illness, a stream of ideas and innovations, and there are expanding opportunities for funding and academic advancement. To maximize the chance that CBPR will lead to tangible, lasting health benefits for communities, researchers will need to balance rigorous research with routine adoption of its conduct in ways that respectfully, productively and equally involve local partners. If successful, lessons learned should inform policy and inspire structural changes in healthcare systems and in communities.
Interview with Dr. Allan Ryan
Authors: P. N. Sperryn
Journal: British Journal of Sports Medicine (1981)

PNSAllan, things have changed a lot in the last few years in America.What are the main sports medical changes?AR I think one of the most interesting things is the sudden rapid growth of the American College of Sports Medicine which has grown to 9,000 members, well beyond the prediction of even the most optimistic members of the College.Some people felt that it was growing too rapidly but I do not share that belief.The quality of people coming into the College is very high and this provides the principal source where people representing all different aspects of sports medicine can meet on a regular basis, not only at the annual meeting, but in the regional meetings which are now becoming more active.
Blood letting. Barber-surgeons' shaving and bleeding bowls
Authors: A. L. Abel
Journal: JAMA (1970)

Through the centuries of medicine, blood letting was a common practice. The first European representation of bleeding occurs on a Greek vase c 500 BC, now in the Louvre in Paris. Hippocrates, born at Cos in 460 BC, wrote that "venisection holds first place in conducting the treatment" of "acute infections... hypochondria... internal pains of the liver, heaviness of the spleen... collections of humours." At the time of the birth of Christ, barber-surgeons practiced in ancient Rome; they were called<i>tonsores</i>and cut hair, drew teeth, and bled at the public baths. These treatments continued for hundreds of years. Galen in 200 AD prepared an elaborate treatise on bleeding and on his authority the practice extended to almost every disease and every country. The Arabs continued in Galen's tradition and the Anglo-Saxon leechbooks prescribed bleeding for most conditions. In Europe treatments were taken over by the monasteries, which became the
INDEPENDENT SYNTHESIS OF LIGHT AND HEAVY CHAINS
Authors: Reuven Laskov, Matthew D. Scharff
Journal: The Journal of Experimental Medicine (1974)

The rates of immunoglobulin synthesis have been examined in two MFC-11 cell lines which were independently adapted to tissue culture and in light-chain-producing variants derived from each of them. One cell line synthesized 2.5 pg immunoglobulin/cell/h, while the other synthesized 3.6 pg immunoglobulin/cell/h. The ratio of heavy and light chains in the two cell lines was approximately the same, and the size of the intracellular pool of immunoglobulin was proportioned to the rate of synthesis. Variants which had spontaneously lost the ability to produce heavy chains continued to synthesize light chains at approximately the same rate as their parent cell line.
National comparisons of lung cancer survival in England, Norway and Sweden 2001-2004: differences occur early in follow-up
Authors: L. Holmberg, F. Sandin, F. Bray, M. Richards, J. Spicer, M. Lambe, A. Klint, M. Peake, T. E. Strand, K. Linklater, D. Robinson, H. Moller
Journal: Thorax (2010)

<h3>Background</h3> Countries with a similar expenditure on healthcare within Europe exhibit differences in lung cancer survival. Survival in lung cancer was studied in 2001–2004 in England, Norway and Sweden. <h3>Methods</h3> Nationwide cancer registries in England, Norway and Sweden were used to identify 250 828 patients with lung cancer from England, 18 386 from Norway and 24 886 from Sweden diagnosed between 1996 and 2004, after exclusion of patients registered through death certificate only or with missing, zero or negative survival times. 5-Year relative survival was calculated by application of the period approach. The excess mortality between the countries was compared using a Poisson regression model. <h3>Results</h3> In all subcategories of age, sex and follow-up period, the 5-year survival was lower in England than in Norway and Sweden. The age-standardised survival estimates were 6.5%, 9.3% and 11.3% for men and 8.4%, 13.5% and 15.9% for women in the respective countries in 2001–2004. The difference in excess risk of dying between the countries was predominantly confined to the first year of follow-up. The relative excess risk ratio during the first 3 months of follow-up comparing England with Norway 2001–2004 varied between 1.23 and 1.46, depending on sex and age, and between 1.56 and 1.91 comparing England with Sweden. <h3>Conclusion</h3> Access to healthcare and population awareness are likely to be major reasons for the differences, but it cannot be excluded that diagnostic and therapeutic activity play a role. Future improvements in lung cancer management may be seen early in follow-up.
Validation of High-Sensitivity Troponin I in a 2-Hour Diagnostic Strategy to Assess 30-Day Outcomes in Emergency Department Patients With Possible Acute Coronary Syndrome
Authors: Louise Cullen, Christian Mueller, William A. Parsonage, Karin Wildi, Jaimi H. Greenslade, Raphael Twerenbold, Sally Aldous, Bernadette Meller, Jillian R. Tate, Tobias Reichlin, Christopher J. Hammett, Christa Zellweger, Jacobus P.J. Ungerer, Maria Rubini Gimenez, Richard Troughton, Karsten Murray, Anthony F.T. Brown, Mira Mueller, Peter George, Tamina Mosimann, Dylan F. Flaws, Miriam Reiter, Arvin Lamanna, Philip Haaf, Christopher J. Pemberton, A. Mark Richards, Kevin Chu, Christopher M. Reid, William Frank Peacock, Allan S. Jaffe, Christopher Florkowski, Joanne M. Deely, Martin Than
Journal: Journal of the American College of Cardiology (2013)
Surfactant Protein D, a Marker of Lung Innate Immunity, Is Positively Associated With Insulin Sensitivity
Authors: José Manuel Fernández-Real, Sergio Valdés, Melania Manco, Berta Chico, Patricia Botas, Arantza Campo, Roser Casamitjana, Elías Delgado, Javier Salvador, Gema Fruhbeck, Geltrude Mingrone, Wifredo Ricart
Journal: Diabetes Care (2010)

Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations.Serum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort.In the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss.These findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.
Occult Nodal Metastasis in Non–Small-Cell Lung Cancer: Implications for the Radiation Oncologist
Authors: Nitin Ohri, Bo Lu, Maria Werner-Wasik
Journal: Journal of Clinical Oncology (2012)

We congratulate Rusch et al 1 for performing the well-designed and thought-provoking ACOSOG (American College of Surgeons Oncology Group) Z0040 trial, which was recently reported in Journal of Clinical Oncology.In their study, occult nodal metastasis was detected in 22% of patients with histologic N0 disease and associated with decreased disease-free and overall survival.These findings are consistent with prior reports from other groups. 2,3Rusch et al correctly indicate that immunohistochemical evaluation of lymph nodes should be incorporated into future trials of adjuvant chemotherapy.We wish to point out that the presence of occult nodal disease may also have implications in decisions regarding postoperative radiotherapy.After initial treatment with complete surgical resection, National Comprehensive Cancer Network guidelines recommend postoperative radiotherapy for patients with N2 disease but not for patients with N0 to N1 disease.These recommendations are largely based on trials using outdated techniques, 4 nonrandomized comparisons, 5 and retrospective reviews. 6Further study is required to define optimal treatment algorithms when modern staging procedures, surgical techniques, systemic therapy, and radiotherapy are available.The ongoing Lung ART (Lung Adjuvant Radiotherapy Trial) study is re-examining the role of adjuvant radiotherapy for N2 disease. 7A recent review of patients with non-small-cell lung cancer with pathologic N1 disease showed that the thorax was the most common site of initial disease progression, especially for patients who received systemic therapy. 8his suggests that adjuvant radiotherapy may be worth revisiting in the setting of N1 disease as well.An analysis of failure patterns in ACASOG Z0040 would be of great interest.If occult nodal metastasis were associated with increased risk of locoregional failure, it would strengthen the case for studying adjuvant radiotherapy in selected patients.Occult nodal metastasis could theoretically be associated with a subtype of non-small-cell lung cancer that preferentially spreads via regional lymphatics.This is supported by the fact that no association between occult lymph node metastasis and occult bone marrow involvement was detected in ACASOG Z0040.Thus, identification of occult nodal disease might help identify patients who are likely to benefit from postoperative radiotherapy.
Abnormalities in ?-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure
Authors: A Mendes Ribeiro
Journal: Cardiovascular Research (2001)

Patients with chronic renal and heart failure present with hypertension and widespread vasoconstriction, respectively. Although systemic release of nitric oxide (NO) may be elevated in both pathological syndromes, enhanced production of NO fails to overcome endothelial dysfunction. Plasma concentrations of L-arginine, a cationic amino acid precursor for NO synthesis, are reduced whilst levels of the endogenous L-arginine analogues, asymmetric and symmetric dimethyl arginine and N(G)-monomethyl-L-arginine, seem to be elevated. We have reported that transport of L-arginine via the cationic amino acid transporters y(+)/CAT and/or y(+)L are up-regulated in erythrocytes, peripheral blood mononuclear cells and platelets from both patients with either chronic renal or heart failure. A possible explanation why NO serves as a failing counter-regulatory mechanism in both these pathologies is that availability of L-arginine for NO production is reduced despite the observed increase in membrane transport. This review examines the mechanisms underlying alterations in NO production in chronic renal and heart failure, and the possible role of L-arginine transport in vascular and platelet dysfunction observed in both syndromes.
Photofrin Uptake in the Tumor and Normal Tissues of Patients Receiving Intraperitoneal Photodynamic Therapy
Authors: Stephen M. Hahn, Mary E. Putt, James Metz, Daniel B. Shin, Elizabeth Rickter, Chandrakala Menon, Debbie Smith, Eli Glatstein, Douglas L. Fraker, Theresa M. Busch
Journal: Clinical Cancer Research (2006)

A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues.Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models.Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (<or=2.31).Some selectivity is found in Photofrin uptake between tumor and normal tissues of the peritoneal cavity, but absolute differences in drug uptake relative to toxicity-limiting normal tissues (intestine) are small. This narrow differential in drug selectivity likely contributes to a narrow window in therapeutic application, which has been previously reported.
EFFECTS OF SURAMIN ON HTLV-III/LAV INFECTION PRESENTING AS KAPOSI'S SARCOMA OR AIDS-RELATED COMPLEX: CLINICAL PHARMACOLOGY AND SUPPRESSION OF VIRUS REPLICATION IN VIVO
Authors: Samuel Broder, JerryM Collins, PhillipD Markham, RobertR Redfield, DanielF Hoth, JeromeE Groopman, RobertC Gallo, Robert Yarchoan, H Clifford Lane, RaymondW Klecker, Hiroaki Mitsuya, Edward Gelmann, Lionel Resnick, CharlesE Myers, AnthonyS Fauci
Journal: The Lancet (1985)