tbuckley/cabot-search huggingface dataset:
Changing Epidemiology of Invasive Pneumococcal Disease Among Older Adults in the Era of Pediatric Pneumococcal Conjugate Vaccine
Authors: Catherine A. Lexau
Journal: JAMA (2005)

ContextA conjugate vaccine targeting 7 pneumococcal serotypes was licensed for young children in 2000. In contrast to the 23-valent polysaccharide vaccine used in adults, the 7-valent conjugate vaccine affects pneumococcal carriage and transmission. Early after its introduction, incidence of invasive pneumococcal disease declined among older adults, a group at high risk for pneumococcal disease.ObjectiveTo determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease, disease characteristics, or the spectrum of patients acquiring these illnesses have changed over the 4 years since pneumococcal conjugate vaccine licensure.Design, Setting, and PopulationPopulation-based surveillance of invasive pneumococcal disease in 8 US geographic areas (total population, 18 813 000), 1998-2003.Main Outcome MeasuresIncidence of invasive pneumococcal disease by pneumococcal serotype and other characteristics; frequency among case patients of comorbid conditions and other factors influencing mortality.ResultsIncidence of invasive pneumococcal disease among adults aged 50 years or older declined 28% (95% confidence interval [CI], −31% to −24%), from 40.8 cases/100 000 in 1998-1999 to 29.4 in 2002-2003. Among those aged 65 years or older, the 2002-2003 rate (41.7 cases/100 000) was lower than the Healthy People 2010 goal (42 cases/100 000). Among adults aged 50 years or older, incidence of disease caused by the 7 conjugate vaccine serotypes declined 55% (95% CI, −58% to −51%) from 22.4 to 10.2 cases/100 000. In contrast, disease caused by any of the 16 serotypes only in polysaccharide vaccine did not change, and disease caused by serotypes not in either vaccine increased somewhat, from 6.0 to 6.8 cases/100 000 (13%; 95% CI, 1% to 27%). Between 1998-1999 and 2002-2003, the proportion of case-patients with human immunodeficiency virus infection increased from 1.7% (47/2737) to 5.6% (124/2231) (P&lt;.001), and those with any comorbid condition that is an indication for pneumococcal polysaccharide vaccination increased from 62.3% (1842/2955) to 72.0% (1721/2390) (P&lt;.001).ConclusionsOur findings indicate that use of conjugate vaccine in children has substantially benefited older adults. However, persons with certain comorbid conditions may benefit less than healthier persons from the indirect effects of the new vaccine.
Impact of TB on the survival of people living with HIV infection in England, Wales and Northern Ireland
Authors: Dominik Zenner, Ibrahim Abubakar, Stefano Conti, Rishi K Gupta, Zheng Yin, Meaghan Kall, Michelle Kruijshaar, Brian Rice, H Lucy Thomas, Anton Pozniak, Marc Lipman, Valerie Delpech
Journal: Thorax (2015)

<h3>Introduction</h3> The impact of TB disease on survival in people living with HIV in high resource settings is not well documented in the antiretroviral treatment (ART) era. We calculated TB incidence rates and compared the mortality of persons with and without HIV-TB in a UK HIV cohort in the post-ART era, to determine the impact of HIV-TB on survival in the UK. <h3>Methods</h3> We linked the national cohort of persons (aged ≥15 years) diagnosed with HIV between 2000 and 2008 in England, Wales and Northern Ireland with the national TB register and deaths from the Office of National Statistics. We compared all-cause and AIDS-specific mortality in patients with and without TB by estimating HRs using Cox regression modelling allowing for potential predictors. <h3>Results</h3> Overall, 3188 (7.2%) individuals developed TB infection among a cohort of 44 050 HIV-diagnosed persons and 149 663 person-years. The cumulative TB incidence rate was 2.13 per 100 person-years with a spike within the first 6 months after HIV diagnosis. TB coinfected patients comprised 18% of the 1880 deaths during follow-up and 79% of deaths (n=967) in the year following HIV diagnosis. TB coinfection (HR 4.77, 95% CI 4.11 to 5.54) was significantly associated with increased all-cause mortality. Analysis of AIDS-related survival showed similar results. <h3>Discussion</h3> The unexpected high mortality in patients with HIV-TB in a population with good healthcare access and ART availability highlights the importance of improving active and latent TB case-finding among patients with HIV, and HIV-testing among patients with TB, to ensure appropriate and prompt treatment initiation for both diseases.
Elevation of Circulating and Ventricular Adrenomedullin in Human Congestive Heart Failure
Authors: Michihisa Jougasaki, Chi-Ming Wei, Linda J. McKinley, John C. Burnett
Journal: Circulation (1995)

Background Adrenomedullin (ADM) is a newly discovered vasodilating and natriuretic peptide that may play an important role in cardiorenal regulation. Although ADM was originally isolated from human pheochromocytoma, ADM-like immunoreactivity has also been widely detected in various tissues, including the cardiovascular system. Methods and Results In view of reports that ADM circulates in the body and that ADM gene and ADM-like immunoreactivity are present in the heart, the present study was designed to determine the plasma concentration of ADM in healthy subjects and in patients with congestive heart failure (CHF) and to investigate the immunohistochemical presence and localization of ADM in normal and failing human hearts. Plasma ADM concentration was 13.2±2.3 pg/mL in healthy subjects (n=11) and increased to 47.3±6.7 pg/mL in patients with CHF (n=11, P &lt;.05 versus normal). Human cardiac tissues were obtained from five patients with end-stage CHF undergoing cardiac transplantation. Five normal donor hearts that were used for cardiac transplantation served as sources for normal atrial tissues. Normal ventricular myocardium was also obtained by endomyocardial biopsy from the right ventricles of these donor hearts immediately before cardiac transplantation. Positive immunostaining was detected within the myocardia in both atria and ventricles of healthy and severely failing human transplanted hearts and was more intense in the atria than in the ventricles. Although there were no significant differences in the intensity of immunoreactivity between normal and failing atria, ADM immunoreactivity was significantly more intense in the ventricular myocytes from failing hearts compared with normal hearts. Conclusions The present study demonstrates that plasma concentration of ADM is increased in patients with CHF and that ADM is present in the human heart. ADM immunoreactivity is markedly increased in the failing human ventricle, suggesting that ventricular ADM expression may be influenced by the circumstances associated with CHF. This supports a potential role for this newly identified vasoactive and natriuretic peptide, ADM, in the neurohumoral activation that characterizes human CHF.
Inhibition of Human Cancer Cell Growth and Metastasis in Nude Mice by Oral Intake of Modified Citrus Pectin
Authors: P. Nangia-Makker, V. Hogan, Y. Honjo, S. Baccarini, L. Tait, R. Bresalier, A. Raz
Journal: JNCI Journal of the National Cancer Institute (2002)

The role of dietary components in cancer progression and metastasis is an emerging field of clinical importance. Many stages of cancer progression involve carbohydrate-mediated recognition processes. We therefore studied the effects of high pH- and temperature-modified citrus pectin (MCP), a nondigestible, water-soluble polysaccharide fiber derived from citrus fruit that specifically inhibits the carbohydrate-binding protein galectin-3, on tumor growth and metastasis in vivo and on galectin-3-mediated functions in vitro.In vivo tumor growth, angiogenesis, and metastasis were studied in athymic mice that had been fed with MCP in their drinking water and then injected orthotopically with human breast carcinoma cells (MDA-MB-435) into the mammary fat pad region or with human colon carcinoma cells (LSLiM6) into the cecum. Galectin-3-mediated functions during tumor angiogenesis in vitro were studied by assessing the effect of MCP on capillary tube formation by human umbilical vein endothelial cells (HUVECs) in Matrigel. The effects of MCP on galectin-3-induced HUVEC chemotaxis and on HUVEC binding to MDA-MB-435 cells in vitro were studied using Boyden chamber and labeling assays, respectively. The data were analyzed by two-sided Student's t test or Fisher's protected least-significant-difference test.Tumor growth, angiogenesis, and spontaneous metastasis in vivo were statistically significantly reduced in mice fed MCP. In vitro, MCP inhibited HUVEC morphogenesis (capillary tube formation) in a dose-dependent manner. In vitro, MCP inhibited the binding of galectin-3 to HUVECs: At concentrations of 0.1% and 0.25%, MCP inhibited the binding of galectin-3 (10 micro g/mL) to HUVECs by 72.1% (P =.038) and 95.8% (P =.025), respectively, and at a concentration of 0.25% it inhibited the binding of galectin-3 (1 micro g/mL) to HUVECs by 100% (P =.032). MCP blocked chemotaxis of HUVECs toward galectin-3 in a dose-dependent manner, reducing it by 68% at 0.005% (P<.001) and inhibiting it completely at 0.1% (P<.001). Finally, MCP also inhibited adhesion of MDA-MB-435 cells, which express galectin-3, to HUVECs in a dose-dependent manner.MCP, given orally, inhibits carbohydrate-mediated tumor growth, angiogenesis, and metastasis in vivo, presumably via its effects on galectin-3 function. These data stress the importance of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer.
Phosphatidylinositol 3-Kinase Controls Antineutrophil Cytoplasmic Antibodies—Induced Respiratory Burst in Human Neutrophils
Authors: Ralph Kettritz, Mira Choi, Waseem Butt, Madhavi Rane, Susanne Rolle, Friedrich C. Luft, Jon B. Klein
Journal: Journal of the American Society of Nephrology (2002)

Antineutrophil cytoplasmic antibodies (ANCA) activate human polymorphonuclear neutrophils (PMN) primed with tumor necrosis factor alpha (TNF-alpha) in vitro. Phosphatidylinositol 3-kinase (PI3-K) and the protein-serine/threonine kinase Akt have been implicated in the control of the phagocyte respiratory burst. The hypothesis that PI3-K controls the ANCA-induced respiratory burst was tested. TNF-alpha-primed PMN were stimulated with a monoclonal antibody to myeloperoxidase (MPO) and with PR3- and MPO-ANCA, respectively. Akt activation was assessed with phospho-specific antibodies. Superoxide release was measured with ferricytochrome. ANCA antigen translocation was assessed by fluorescence-activated cell sorter. The effect of TNF-alpha and MPO-ANCA on Akt signaling was studied with immunoprecipitation and glutathione S-transferase pull-down assays. Western blotting revealed rapid transient Akt phosphorylation during TNF-alpha priming and a second phosphorylation after ANCA. PI3-K inhibition by LY294002 blocked both Akt phosphorylation and superoxide generation. A total of 20 +/- 3 nmol O(2)(-)/0.75 x 10(6) PMN/45 min was released after stimulation with PR3-ANCA. LY294002 (5 microM) decreased this amount to 0.3 +/- 2.6 nmol (n = 10, P < 0.05); the MPO-ANCA values were 23 +/- 3 versus 1.6 +/- 3.6 (n = 10, P < 0.05). p38 MAPK inhibition with 10 microM SB202190 that also decreased ANCA-induced superoxide generation prevented S473 phosphorylation of Akt in response to TNF-alpha and to ANCA. However, SB202190 but not LY294002 abrogated TNF-alpha-mediated ANCA antigen surface translocation, demonstrating that superoxide generation and ANCA antigen translocation proceed by separate mechanisms. Akt, PAK1, and Rac1 existed as cytosolic complex in resting PMN. TNF-alpha stimulation increased association of PAK1 with Akt. An MPO monoclonal antibody did not alter the Akt signaling complex further. The data demonstrate the importance of PI3-K for the ANCA-induced PMN oxidant production.
Failure of sustained response to etanercept and refractoriness to anakinra in patients with T50M TNF-receptor-associated periodic syndrome
Authors: N. Quillinan, G. Mannion, A. Mohammad, R. Coughlan, L. J. Dickie, M. F. McDermott, D. McGonagle
Journal: Annals of the Rheumatic Diseases (2011)

TNF-receptor-associated periodic syndrome (TRAPS) is an autoinflammatory condition and is the most common autosomal dominant hereditary periodic fever. Autoinflammatory syndromes are distinguished from autoimmune diseases by the fact that their disease immunopathology is largely played out by cells and molecules of the innate immune system.1 2

The pathogenesis of TRAPS is still not completely understood and treatment options are extremely limited. Prednisolone improves symptoms during attacks but the effect often wanes and patients may require increasing doses. Etanercept, a TNFR2 fusion protein, is reported to have a beneficial effect on many patients with TRAPS,3,–,6 whereas infliximab is not generally effective in most cases of TRAPS and may cause an overwhelming flare but occasional benefit has also been described.7,–,9 Anakinra, …
Functional Changes During High Output Failure Produced by Daily Hemorrhage in Dogs with Pulnionic Stenosis
Authors: JAMES O. DAVIS, M. Jay GOODKIND, WILMOT C. BALL, Alfred Casper
Journal: Circulation Research (1957)

The relationship of changes in cardiovascular and renal hemodynamic function to sodium excretion has been studied following daily hemorrhage in dogs with pulmonic stenosis and in normal dogs. The animals with pulmonic stenosis developed signs of right heart failure, but the normal dogs failed to show evidence of cardiac decompensation during the course of the anemia. The two most striking differences in the responses of the 2 groups of dogs were the increase in mean right atrial pressure and the occurrence of sodium retention, both of which were observed only in the dogs with pulmonic stenosis. The increase in cardiac output and the renal functional changes were similar in the 2 groups of animals; glomerular filtration rate was unchanged or increased in the majority of dogs with pulmonic stenosis and heart failure.
Complications with I.U.D.S.
Authors: D. Wolfers
Journal: BMJ (1969)

SIR,-Referring to your leading article "Radiology's New Chance " (24 May, p. 464), I would like to emphasize two points.You state with regard to radiodiagnosis " at present the specialty lacks enough recruits."This statement was true two years ago but is less so now.In 1968 the Faculty of Radiologists held discussions with the Department of Health and Social Security.The latter was most helpful and many new training posts were created in England and Wales.As a result an increased
A Cost-Benefit Comparison of Intensive Diabetes Management With Implantable Pumps Versus Multiple Subcutaneous Injections in Patients With Type I Diabetes
Authors: Marie-Joelle Haardt, Jean-Louis Selam, Gerard Slama, Jean-Pierre Bethoux, Catherine Dorange, Brigitte Mace, Marie-Lou Ramaniche, Françoise Bruzzo
Journal: Diabetes Care (1994)

OBJECTIVE To investigate if intraperitoneal (IP) insulin infusion via programmable implantable pumps is a potential alternative to subcutaneous (SC) insulin via multiple injections. RESEARCH DESIGN AND METHODS We compared the cost-benefits of the two methods using a randomized, prospective, 6-month, crossover design in 10 adult type I diabetic patients. RESULTS When judged on the last month of IP versus SC periods in the nine patients who completed the study, metabolic data showed better glycemie control (HbA1c: 7.2 ± 0.2 IP vs. 8.5 ± 0.7% SC, mean ± SE, P = 0.02), reduced glycemie fluctuations (SD of capillary glucose values: 3.4 ± 0.2 IP vs. 4.6 ± 0.2 mM SC, P &amp;gt; 0.01), and fewer mild hypoglycemie events (5.7±2.0 IP vs. 10.0 ± 3.1 events/month SC, P = 0.02). Quality of life, judged by Diabetes Control and Complications Trial questionnaires, was unaffected by pump therapy. Direct costs, including pump acquisition, implantation, and follow-up, were 2.6-fold higher with IP than with SC delivery. CONCLUSIONS The implantable pump is more effective in the short term, equally accepted, but more costly than multiple injections and should be limited to patients with unsatisfactory glycemie control despite intensive diabetes management with SC insulin. In addition, longer-term, larger-scale, and comparative evaluation is required.
Identification and Characterization of a Membrane Receptor for Proteolysis-Inducing Factor on Skeletal Muscle
Authors: Penio T. Todorov, Stacey M. Wyke, Michael J. Tisdale
Journal: Cancer Research (2007)

Proteolysis-inducing factor (PIF) is a sulfated glycoprotein produced by cachexia-inducing tumors, which induces atrophy of skeletal muscle. PIF has been shown to bind specifically with high affinity (K(d), in nanomolar) to sarcolemma membranes from skeletal muscle of both the mouse and the pig, as well as murine myoblasts and a human muscle cell line. Ligand binding was abolished after enzymatic deglycosylation, suggesting that binding was mediated through the oligosaccharide chains in PIF. Chondroitin sulfate, but not heparan or dermatan sulfate, showed competitive inhibition (K(d), 1.1 x 10(-7) mol/L) of binding of PIF to the receptor, suggesting an interaction with the sulfated oligosaccharide chains. Ligand blotting of [(35)S]PIF to triton solublized membranes from C(2)C(12) cells provided evidence for a binding protein of apparent M(r) of approximately 40,000. Amino acid sequence analysis showed the PIF receptor to be a DING protein. Antisera reactive to a 19mer from the N-terminal amino acid residues of the binding protein attenuated protein degradation and activation of the ubiquitin-proteasome pathway induced by PIF in murine myotubes. In addition, the antisera was highly effective in attenuating the decrease in body weight in mice bearing the MAC16 tumor, with a significant increase in muscle wet weight due to an increase in the rate of protein synthesis, together with a reduction in protein degradation through attenuation of the increased proteasome expression and activity. These results confirm that the PIF binding protein has a functional role in muscle protein atrophy in cachexia and that it represents a potential new therapeutic target.
Association of Established Smoking Among Adolescents With Timing of Exposure to Smoking Depicted in Movies
Authors: B. A. Primack, M. R. Longacre, M. L. Beach, A. M. Adachi-Mejia, L. J. Titus, M. A. Dalton
Journal: JNCI Journal of the National Cancer Institute (2012)

It is not known whether exposure to smoking depicted in movies carries greater influence during early or late adolescence. We aimed to quantify the independent relative contribution to established smoking of exposure to smoking depicted in movies during both early and late adolescence. We prospectively assessed 2049 nonsmoking students recruited from 14 randomly selected public schools in New Hampshire and Vermont. At baseline enrollment, students aged 10–14 years completed a written survey to determine personal, family, and sociodemographic characteristics and exposure to depictions of smoking in the movies (early exposure). Seven years later, we conducted follow-up telephone interviews to ascertain follow-up exposure to movie smoking (late exposure) and smoking behavior. We used multiple regression models to assess associations between early and late exposure and development of established smoking. One-sixth (17.3%) of the sample progressed to established smoking. In analyses that controlled for covariates and included early and late exposure in the same model, we found that students in the highest quartile for early exposure had 73% greater risk of established smoking than those in the lowest quartile for early exposure (27.8% vs 8.6%; relative risk for Q4 vs Q1 = 1.73, 95% confidence interval = 1.14 to 2.62). However, late exposure to depictions of smoking in movies was not statistically significantly associated with established smoking (22.1% vs 14.0%; relative risk for Q4 vs Q1 = 1.13, 95% confidence interval = 0.89 to 1.44). Whereas 31.6% of established smoking was attributable to early exposure, only an additional 5.3% was attributable to late exposure. Early exposure to smoking depicted in movies is associated with established smoking among adolescents. Educational and policy-related interventions should focus on minimizing early exposure to smoking depicted in movies.
Surgical versus Nonsurgical Treatment for Lumbar Degenerative Spondylolisthesis
Authors: James N. Weinstein, Jon D. Lurie, Tor D. Tosteson, Brett Hanscom, Anna N.A. Tosteson, Emily A. Blood, Nancy J.O. Birkmeyer, Alan S. Hilibrand, Harry Herkowitz, Frank P. Cammisa, Todd J. Albert, Sanford E. Emery, Lawrence G. Lenke, William A. Abdu, Michael Longley, Thomas J. Errico, Serena S. Hu
Journal: New England Journal of Medicine (2007)

Management of degenerative spondylolisthesis with spinal stenosis is controversial. Surgery is widely used, but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials.Surgical candidates from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a randomized cohort or an observational cohort. Treatment was standard decompressive laminectomy (with or without fusion) or usual nonsurgical care. The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) bodily pain and physical function scores (100-point scales, with higher scores indicating less severe symptoms) and the modified Oswestry Disability Index (100-point scale, with lower scores indicating less severe symptoms) at 6 weeks, 3 months, 6 months, 1 year, and 2 years.We enrolled 304 patients in the randomized cohort and 303 in the observational cohort. The baseline characteristics of the two cohorts were similar. The one-year crossover rates were high in the randomized cohort (approximately 40% in each direction) but moderate in the observational cohort (17% crossover to surgery and 3% crossover to nonsurgical care). The intention-to-treat analysis for the randomized cohort showed no statistically significant effects for the primary outcomes. The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years. The treatment effects at 2 years were 18.1 for bodily pain (95% confidence interval [CI], 14.5 to 21.7), 18.3 for physical function (95% CI, 14.6 to 21.9), and -16.7 for the Oswestry Disability Index (95% CI, -19.5 to -13.9). There was little evidence of harm from either treatment.In nonrandomized as-treated comparisons with careful control for potentially confounding baseline factors, patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically. (ClinicalTrials.gov number, NCT00000409 [ClinicalTrials.gov].).