tbuckley/cabot-search huggingface dataset:
Rationale for the use of non-invasive ventilation in chronic ventilatory failure
Authors: P M Turkington
Journal: Thorax (2000)

In recent years there has been a rapid growth of interest in the use of non-invasive ventilation (NIV) in the management of patients with acute and chronic ventilatory failure.This paper reviews the evidence for the eVectiveness of NIV in the management of chronic hypercapnic ventilatory failure and discusses possible mechanisms by which NIV has an eVect. Evidence base for the use of NIV in chronic ventilatory failure SLOWLY PROGRESSIVE NEUROMUSCULAR DISEASE AND CHEST WALL DISORDERS2][3][4][5] In a large case series Leger et al 6 reported on 276 patients with chronic ventilatory failure.In patients with kyphoscoliosis or sequelae of previous tuberculosis (usually thoracoplasty) they found a significant improvement in diurnal arterial oxygen and carbon dioxide tensions (PaO 2 and PaCO 2 ) and a reduction in the need for hospitalisation for respiratory illness following the introduction of NIV; 62% of the patients reported improvement in their quality of sleep and 70% reported improvements in activities of daily living.NIV was continued for two years by 80% of the kyphoscoliosis group, 76% of the patients who had sequelae of previous tuberculosis, and 56% of the patients with Duchenne-type muscular dystrophy (DMD).In a further uncontrolled study Simonds and Elliott 7 reported the five year actuarial probability of continuing NIV in patients with scoliosis, previous polio, post tuberculous lung disease, and generalised neuromuscular disorders to be 79%, 100%, 94%, and 81%, respectively.After one year of NIV arterial blood gas tensions recorded during spontaneous breathing by day showed that, compared with the pretreatment value, PaO 2 increased by a mean (SD) of 1.8 (1.9) kPa and PaCO 2 decreased by 1.4 (1.3) kPa.Quality of life, assessed on one occasion following the introduction of NIV, showed mental health, energy and vitality scores of the short form 36 8 similar to the UK population norms; the remaining domains were similar to other
Housing and Public Health
Authors: Mary Shaw
Journal: Annual Review of Public Health (2004)

This review considers the broad area of housing and public health, one of the traditional and core areas of public health research and intervention. The review takes into account the range of factors, acting at different levels, directly and indirectly, through which housing affects health. In public health terms, housing affects health in a myriad of relatively minor ways, in total forming one of the key social determinants of health. The paper closes by considering how the improvement of housing and neighborhoods has been a core activity of public health and a central component in tackling poverty. Investment in housing can be more than an investment in bricks and mortar: It can also form a foundation for the future health and well-being of the population. Addressing poor-quality housing and detrimental neighborhoods, in the broadest sense, is thus a task that should be grasped with vigor and determination by all those involved in public health.
Comparison of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event suggestive of multiple sclerosis (REFLEX): a phase 3 randomised controlled trial
Authors: Giancarlo Comi, Nicola De Stefano, Mark S Freedman, Frederik Barkhof, Chris H Polman, Bernard MJ Uitdehaag, Florence Casset-Semanaz, Brian Hennessy, Margaretha Stam Moraga, Sanda Rocak, Bettina Stubinski, Ludwig Kappos
Journal: The Lancet Neurology (2011)
Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo
Authors: Qi Ling, Andrew T. Jacovina, Arunkumar Deora, Maria Febbraio, Ronit Simantov, Roy L. Silverstein, Barbara Hempstead, Willie H. Mark, Katherine A. Hajjar
Journal: Journal of Clinical Investigation (2004)

A central tenet of fibrinolysis is that tissue plasminogen activator–dependent (t-PA– dependent) conversion of plasminogen to active plasmin requires the presence of the cofactor/substrate fibrin. However, previous in vitro studies have suggested that the endothelial cell surface protein annexin II can stimulate t-PA–mediated plasminogen activation in the complete absence of fibrin. Here, homozygous annexin II–null mice displayed deposition of fibrin in the microvasculature and incomplete clearance of injury-induced arterial thrombi. While these animals demonstrated normal lysis of a fibrin-containing plasma clot, t-PA–dependent plasmin generation at the endothelial cell surface was markedly deficient. Directed migration of annexin II–null endothelial cells through fibrin and collagen lattices in vitro was also reduced, and an annexin II peptide mimicking sequences necessary for t-PA binding blocked endothelial cell invasion of Matrigel implants in wild-type mice. In addition, annexin II–deficient mice displayed markedly diminished neovascularization of fibroblast growth factor–stimulated cornea and of oxygen-primed neonatal retina. Capillary sprouting from annexin II–deficient aortic ring explants was markedly reduced in association with severe impairment of activation of metalloproteinase-9 and -13. These data establish annexin II as a regulator of cell surface plasmin generation and reveal that impaired endothelial cell fibrinolytic activity constitutes a barrier to effective neoangiogenesis.
THE RETICULAR MATERIAL OF DEVELOPING BLOOD CELLS
Authors: Edmund V. Cowdry
Journal: The Journal of Experimental Medicine (1921)

Erythroblasts, leucocytes, and lymphocytes resemble other cells of the body in containing a restricted area of fluidity in their cytoplasm. In special preparations this fluid appears in the form of a more or less complicated reticulum which seems to be continually but slowly changing in shape. For convenience the fluid may provisionally be referred to as reticular material, emphasis being laid on its composition rather than its form. As a working hypothesis it is safe to assume that the chemical and physical properties of this material vary in cells of different kinds as well as in different stages in the activity of the same cell. The conclusion that it is "identical" in different cells, because the present crude methods of technique reveal no fundamental differences, would be as incorrect as the statement that the serum of different animals is identical, because no difference is observed on microscopic examination.
Human autoantibodies against a desmosomal core protein in pemphigus foliaceus.
Authors: L Koulu, A Kusumi, M S Steinberg, V Klaus-Kovtun, J R Stanley
Journal: The Journal of Experimental Medicine (1984)

Pemphigus foliaceus (PF) is a human autoimmune disease in which antibodies are directed against the cell surface of epidermal cells with resultant blister formation. The histopathology of these blisters indicates that cells have detached from each other, and electron microscopy of early blisters shows diminished numbers, to complete loss, of desmosomes as well as abnormalities of the tonofilament-desmosome complex. In this study we demonstrate that autoantibodies from certain PF patients bind to a desmosomal core glycoprotein called desmoglein (DG) I. Proteins in extracts of normal human epidermis were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE), then transferred to nitrocellulose or 2-aminophenylthioether paper for immunoperoxidase staining. Results of these immunoblots indicated that sera from 6 of 13 PF patients specifically and intensely stained an approximately 160,000 mol wt polypeptide, "PF antigen". Such staining was not seen with normal human sera or sera from patients with pemphigus vulgaris or bullous pemphigoid, two autoimmune blistering skin diseases that are clinically, histologically, and immunochemically distinct from PF. However, rabbit antiserum directed against DGI, that was isolated from bovine muzzle desmosomes, stained a polypeptide band which co-migrated with PF antigen. Furthermore, when proteins from extracts of normal human epidermis were electrophoresed in two dimensions (isoelectric focusing, then SDS-PAGE) before transfer to nitrocellulose for immunoperoxidase staining, PF antibodies and antibodies to DGI stained identical spots. Finally, PF sera as well as PF IgG that was affinity purified with PF antigen from normal human epidermis, both selectively bound to DGI extracted from bovine muzzle desmosomes. These studies demonstrate that the human autoantibodies from certain patients with PF, a disease of epidermal cell adhesion, are directed against a desmosomal core protein.
Pregnancy in the Sixth Decade of Life
Authors: Richard J. Paulson, Robert Boostanfar, Peyman Saadat, Eliran Mor, David E. Tourgeman, Cristin C. Slater, Mary M. Francis, John K. Jain
Journal: JAMA (2002)

As a result of oocyte donation, women in their sixth decade of life are now able to conceive and carry pregnancies to term. However, little is known about pregnancy outcomes in this population.To describe pregnancy outcomes in women aged 50 years or older who conceived after in vitro fertilization with donor oocytes.Retrospective analysis of cycles conducted at a US university assisted reproduction program during calendar years 1991-2001.Seventy-seven postmenopausal women with no chronic medical conditions (mean [SD] age, 52.8 [2.9] years; range, 50-63 years) who underwent 121 embryo transfer procedures (89 fresh and 32 frozen). Pregnancy outcomes were ascertained by chart review and telephone follow-up.Maternal and neonatal outcomes.There were 55 clinical pregnancies for a total pregnancy rate of 45.5%. The live birth rate was 37.2%. Of the 45 live births, 31 were singletons, 12 were twins, and 2 were triplets, for which the mean (SD) gestational ages at delivery were 38.4 (2.1) weeks, 35.8 (2.8) weeks, and 32.2 weeks, respectively. Mean (SD) birth weights were 3039 g (703 g), 2254 g (581 g), and 1913 g, respectively. Apgar scores at 1 and 5 minutes were 8.2 (0.9) and 9.1 (0.5), respectively. Of singletons, 68% were delivered by cesarean, and all multiples were delivered by cesarean. Mild preeclampsia was noted in 25% of patients and severe preeclampsia in 10%. Gestational diabetes required diet modification in 17.5%, and 2.5% required insulin.Appropriately screened women aged 50 years or older can successfully conceive via oocyte donation and experience similar pregnancy rates, multiple gestation rates, and spontaneous abortion rates as younger recipients. During pregnancy, they appear at increased risk of preeclampsia and gestational diabetes. A majority can expect to deliver via cesarean. However, there does not appear to be any definitive medical reason for excluding these women from attempting pregnancy on the basis of age alone.
Spontaneous Development of Plasmacytoid Tumors in Mice with Defective Fas–Fas Ligand Interactions
Authors: Wendy F. Davidson, Thomas Giese, Torgny N. Fredrickson
Journal: The Journal of Experimental Medicine (1998)

B cell malignancies arise with increased frequency in aging individuals and in patients with genetic or acquired immunodeficiency (e.g., AIDS) or autoimmune diseases. The mechanisms of lymphomagenesis in these individuals are poorly understood. In this report we investigated the possibility that mutations at the Fas (lpr) and Fasl (gld) loci, which prevent Fas-mediated apoptosis and cause an early onset benign lymphoid hyperplasia and autoimmunity, also predispose mice to malignant lymphomas later in life. Up to 6 mo of age, hyperplasia in lpr and gld mice results from the predominant accumulation of polyclonal T cell subsets and smaller numbers of polyclonal B cells and plasma cells. Here, we examined C3H-lpr, C3H-gld, and BALB-gld mice 6-15 mo of age for the emergence of clonal T and B cell populations and found that a significant proportion of aging mice exclusively developed B cell malignancies with many of the hallmarks of immunodeficiency-associated B lymphomas. By 1 yr of age, approximately 60% of BALB-gld and 30% of C3H-gld mice had monoclonal B cell populations that grew and metastasized in scid recipients but in most cases were rejected by immunocompetent mice. The tumors developed in a milieu greatly enriched for plasma cells, CD23- B cells and immunodeficient memory T cells and variably depleted of B220+ DN T cells. Growth factor-independent cell lines were established from five of the tumors. The majority of the tumors were CD23- and IgH isotype switched and a high proportion was CD5+ and dull Mac-1+. Considering their Ig secretion and morphology in vivo, most tumors were classified as malignant plasmacytoid lymphomas. The delayed development of the gld tumors indicated that genetic defects in addition to the Fas/Fasl mutations were necessary for malignant transformation. Interestingly, none of the tumors showed changes in the genomic organization of c-Myc but many had one or more somatically-acquired MuLV proviral integrations that were transmitted in scid passages and cell lines. Therefore, insertional mutagenesis may be a mechanism for transformation in gld B cells. Our panel of in vivo passaged and in vitro adapted gld lymphomas will be a valuable tool for the future identification of genetic abnormalities associated with B cell transformation in aging and autoimmune mice.
Secular Trends in Colon and Rectal Cancer Relative Survival
Authors: C. M. Rutter, E. A. Johnson, E. J. Feuer, A. B. Knudsen, K. M. Kuntz, D. Schrag
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundTreatment options for colorectal cancer (CRC) have improved substantially over the past 25 years. Measuring the impact of these improvements on survival outcomes is challenging, however, against the background of overall survival gains from advancements in the prevention, screening, and treatment of other conditions. Relative survival is a metric that accounts for these concurrent changes, allowing assessment of changes in CRC survival. We describe stage- and location-specific trends in relative survival after CRC diagnosis.
Randomized Phase II Trial of Cetuximab, Bevacizumab, and Irinotecan Compared With Cetuximab and Bevacizumab Alone in Irinotecan-Refractory Colorectal Cancer: The BOND-2 Study
Authors: Leonard B. Saltz, Heinz-Josef Lenz, Hedy L. Kindler, Howard S. Hochster, Scott Wadler, Paulo M. Hoff, Nancy E. Kemeny, Ellen M. Hollywood, Mithat Gonen, Marcus Quinones, Meroe Morse, Helen X. Chen
Journal: Journal of Clinical Oncology (2007)

We evaluated the safety and efficacy of concurrent administration of two monoclonal antibodies, cetuximab and bevacizumab, in patients with metastatic colorectal cancer.This was a randomized phase II study in patients with irinotecan-refractory colorectal cancer. All patients were naïve to both bevacizumab and cetuximab. Patients in arm A received irinotecan at the same dose and schedule as last received before study entry, plus cetuximab 400 mg/m2 loading dose, then weekly cetuximab 250 mg/m2, plus bevacizumab 5 mg/kg administered every other week. Patients in arm B received the same cetuximab and bevacizumab as those in arm A but without irinotecan.Forty-three patients received cetuximab, bevacizumab, and irinotecan (CBI) and 40 patients received cetuximab and bevacizumab alone (CB). Toxicities were as would have been expected from the single agents. For the CBI arm, time to tumor progression (TTP) was 7.3 months and the response rate was 37%; for the CB arm, TTP was 4.9 months and the response rate was 20%. The overall survival for the CBI arm was 14.5 months and the overall survival for the CB-alone arm was 11.4 months.Cetuximab and bevacizumab can be administered concurrently, with a toxicity pattern that seems to be similar to that which would be expected from the two agents alone. This combination plus irinotecan also seems to be feasible. The activity seen with the addition of bevacizumab to cetuximab, or to cetuximab plus irinotecan, seems to be favorable when compared with historical controls of cetuximab or cetuximab/irinotecan in patients who are naïve to bevacizumab.
Pulmonary vascular involvement in chronic obstructive pulmonary disease
Authors: N.F. Voelkel, C.D. Cool
Journal: European Respiratory Journal (2003)

Chronic obstructive lung disease affects the entire lung, not just the airways. Although pulmonary hypertension (PH) has long been recognised in a subset of patients with COLD, the important pathophysiological questions remain unanswered. Oxygen supplementation, however, has been shown to blunt the exercise-induced PH in these patients. Hypercoagulability has also been described in patients with COLD. This may, in part, be due to the inflammatory aspects of COLD exacerbation events. In addition to perivascular inflammation, the pathology of vessels in COLD includes intimal thickening, muscularisation of arterioles, in situ thrombosis, loss of capillaries and precapillary arterioles, and vascular congestion and stasis. Recent work describes apoptosis of septal endothelial cells and decreased expression of vascular endothelial growth factor (VEGF) and one of its receptors, VEGFRII, in lungs from patients with emphysema. Based on this work, a rat model was developed that shows chronic blockade of VEGF receptors leads to septal cell apoptosis and results in emphysema and PH. This animal model has led to prevention trials using 1) a broad-spectrum caspase inhibitor, 2) a superoxide dismutase mimetic, and 3) α 1 ‐antitrypsin. These findings highlight the importance of vascular endothelial growth factor, apoptosis, oxidative stress and protease activity in the pathogenesis of emphysema. They also underscore the importance of the vasculature in what is traditionally thought of as an airways disease. Future treatment strategies need to address the vascular components of chronic obstructive lung disease.
Pseudoporphyria and sunbeds, a coincidence in identical twins?
Authors: C.L. Wilson, S.S. Mendelsohn
Journal: British Journal of Dermatology (1991)

Journal Article Pseudoporphyria and sunbeds, a coincidence in identical twins? Get access C.L. Wilson, C.L. Wilson Department of Dermatology, Slade Hospital, Oxford, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.S. Mendelsohn S.S. Mendelsohn Chester Royal Infirmary, Chester, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 2, 1 August 1991, Page 191, https://doi.org/10.1111/j.1365-2133.1991.tb06073.x Published: 01 August 1991
Risk factors for bronchial hyperresponsiveness in late childhood and early adolescence
Authors: P. Ernst, H. Ghezzo, M.R. Becklake
Journal: European Respiratory Journal (2002)

The prevalence of asthma and bronchial hyperresponsiveness (BHR) tends to decrease in male children but increase in female children in the transition from childhood to adolescence. Hormonal factors may be involved in the natural history of asthma during this period. In a prospective study of Montreal school children, the authors examined the determinants of BHR according to the child's pubertal status; 156 male children and 168 female children without a prior diagnosis of asthma were followed for an average of 4.6 yrs. Average age at follow-up was 13.4 yrs and 59% had reached puberty. The prevalence of BHR at follow-up was similar among pre- and postpubertal male children (25.0% versus 29.2%),while BHR was more common among post- compared with prepubertal female children (33.1% versus 14.2%). There were no differences in the determinants (measured in childhood) of BHR at follow-up according to pubertal status. The major determinant of BHR was a positive skin test to dust-mite antigen. BHR was also linked to exposure to gas cooking and the presence of exercise-induced bronchospasm. In conclusion, the results of this study do not support a change in asthma phenotype with the onset of puberty. Pre- and postpuberty, the major determinant of bronchial hyperresponsiveness was skin sensitivity to mite allergen.
Effect of Cytarabine and Decitabine in Combination in Human Leukemic Cell Lines
Authors: Taichun Qin, Emile M. Youssef, Jaroslav Jelinek, Rong Chen, Allen S. Yang, Guillermo Garcia-Manero, Jean-Pierre J. Issa
Journal: Clinical Cancer Research (2007)

Abstract Purpose: 1-β-d-Arabinofuranosylcytosine (cytarabine; ara-C) is the most active agent in myeloid leukemia. 5-Aza-2′-deoxycytidine (DAC) is a cytosine analogue that inhibits DNA methylation and also has activity in myeloid leukemia. Therefore, we investigated combining these two drugs in human leukemia cell lines in vitro. Experimental Design: We initially examined the effects of ara-C and DAC on human leukemia cell lines HL60, ML-1, RAji, and Jurkat. We measured IC50 of DAC and ara-C in these cell lines and calculated a combination index of these two drugs given either simultaneously or sequentially. In searching for mechanisms relative to epigenetic regulation for this effect, we examined DNA methylation of LINE and Alu repetitive elements as a surrogate for global genomic DNA methylation. In addition, we sorted Annexin V positive and negative cells and measured differences in LINE methylation between them. Results: The combination of DAC and ara-C showed additive induction of cell death in ML-1 and synergistic induction in HL60, Raji, and Jurkat. Sequentially, DAC followed by ara-C was a synergistic combination in all cell lines. Low-dose DAC induced more hypomethylation than high doses of the drug, whereas ara-C had no effects on methylation. The combination of ara-C with DAC either together or DAC followed by ara-C resulted in inhibition of LINE demethylation in HL60. The RIL gene, which is silenced by DNA hypermethylation, was activated by DAC, but the addition of ara-C to DAC reduced RIL gene activation. DAC treatment increased H3 Lys9 acetylation of Alu elements, whereas ara-C had no effect, and the addition of ara-C to DAC inhibited this effect. Finally, we showed that after DAC exposure, Annexin V positive cells were more hypomethylated than Annexin V negative cells. Conclusion: The combination of DAC and ara-C showed additive or synergistic effects on cell death in four human leukemia cell lines in vitro, but antagonism in terms of epigenetic effects. One possible explanation for these paradoxical observations is that hypomethylated cells are sensitized to cell killing by ara-C. These data suggest that DAC used in combination with ara-C has clinical potential in the treatment of acute myeloid leukemia.
Paradoxical hypertension after repair of coarctation of the aorta in children: balloon angioplasty versus surgical repair.
Authors: M Choy, A P Rocchini, R H Beekman, A Rosenthal, M Dick, D Crowley, D Behrendt, A R Snider
Journal: Circulation (1987)

The incidence and possible causes of paradoxical hypertension were evaluated in eight children who underwent balloon dilatation and seven children who underwent surgical repair of coarctation of the aorta. Both procedures resulted in a significant reduction in the coarctation gradient. Both systolic and diastolic blood pressures increased in the surgical group after repair, whereas systolic pressures decreased and diastolic pressures remained unchanged after balloon angioplasty. In the surgical group, but not in the balloon angioplasty group, plasma catecholamines and plasma renin activity rose during the first 2 days after relief of the coarctation. The data presented in this report support the hypothesis that the sympathetic nervous system and the renin angiotensin system are important mediators of the paradoxical hypertension that occurs after surgical repair of coarctation. Furthermore, balloon angioplasty of coarctation of the aorta does not stimulate either system and thus paradoxical hypertension is not a complication of this procedure.