tbuckley/cabot-search huggingface dataset:
Iron Kinetics in Man: New Studies with Mouse Hemoglobin
Authors: VIRGIL F. FAIRBANKS
Journal: Annals of Internal Medicine (1973)

Editorial Notes1 August 1973Iron Kinetics in Man: New Studies with Mouse HemoglobinVIRGIL F. FAIRBANKS, M.D., F.A.C.P.VIRGIL F. FAIRBANKS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-2-271 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the complete cycle of iron metabolism, iron flows from transferrin in plasma to the maturing normoblast in the bone marrow and thence into hemoglobin, in which form it circulates in the vascular system for about 4 months. The aged erythrocyte is then phagocytized by cells of the reticuloendothelial system (RES), the hemoglobin molecule is destroyed, and the iron is released. The iron may then return to transferrin in plasma to resume the cycle or it may be retained in storage form (as ferritin or hemosiderin) in the reticuloendothelial system. Iron metabolism thus involves four major compartments: plasma (transferrin), erythroid...References1. FREIREICHROSSBAYLES FJT: Radioactive iron metabolism and erythrocyte survival studies of the mechanism of the anemia associated with rheumatoid arthritis. J Clin Invest 36:1043-1058, 1957 CrossrefMedlineGoogle Scholar2. HAURANIBURKEMARTINEZ FWE: Defective re-utilization of iron in the anemia of inflammation. J Lab Clin Med 65: 560-570, 1965 MedlineGoogle Scholar3. NOYESBOTHWILLFINCH WTC: The role of the reticuloendothelial cell in iron metabolism. Br J Haematol 6: 43-55, 1960 CrossrefMedlineGoogle Scholar4. WEINSTEIN I: A correlative study of the erythrokinetics and disturbances in iron metabolism associated with the anemia of rheumatoid arthritis. Blood 14:950-966, 1959 CrossrefMedlineGoogle Scholar5. DRESCHNAJEAN CY: Hemoglobin iron kinetics in man. Rev Eur Etud Clin Biol 17:930-942, 1972 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1973Volume 79, Issue 2Page: 271-272KeywordsBlood plasmaBone marrowCellsFerritinHemoglobin Issue Published: 1 August 1973 PDF DownloadLoading ...
A Comparison of Pulmonary Arterial Occlusion Algorithms for Estimation of Pulmonary Capillary Pressure
Authors: ANDREW A. PELLETT, ROYCE W. JOHNSON, GERALYNN G. MORRISON, MICHAEL S. CHAMPAGNE, BENNETT P. DeBOISBLANC, MICHAEL G. LEVITZKY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Using the arterial occlusion method, we compared five literature-based estimates of pulmonary capillary pressure (Ppc) with the corresponding double occlusion pressures (Pdo) in anesthetized dogs whose chests had been closed after sternotomy for instrumentation. Arterial occlusions were performed with a balloon-tipped pulmonary artery catheter that housed pressure transducers immediately proximal and distal to the balloon. Separation of the proximal and distal pressure waveforms during balloon inflation allowed us to precisely define the moment of occlusion. We fit a monoexponential curve to pressure data beginning 200 ms after the onset of occlusion and a biexponential curve to data beginning at the instant of occlusion, with data obtained over a range of vascular states (control, serotonin infusion, histamine infusion). In addition, we investigated the use of sampling of the raw data to estimate capillary pressure. Three of the five literature-based estimates of Ppc yielded values similar to Pdo. The optimal (least average difference from Pdo) interpolation/extrapolation time points of the curve fits varied, depending on the type of curve fitting and the state of the pulmonary vasculature. We also determined that a close approximation of Pdo may be derived from the raw data, as an alternative to exponential curve fitting.
PUERPERAL INSANITY: AN ANALYSIS OF ONE HUNDRED AND FORTY CONSECUTIVE CASES
Authors: W. F. Menzies
Journal: American Journal of Psychiatry (1893)

During the years 1889, 1890 and 1891, 968 female patients were admitted into Rainhill Asylum.In 1891 restrictions were placed upon the number received, owing to want of room, but every endeavour was made to accommodate acute cases, and probably no well-established puerperal case was refused.These 968 patients were drawn from the poorer classes, and from an estimated female population of about 455,000.The births in this population were, during the same years, 98,065, a ratio of one case of puerperal insanity in 700 parturitions,
Prospective semistructured observational study to identify risk attributable to staff deployment, training, and updating opportunities for midwives
Authors: B. Ashcroft
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To identify potential risk or mishap in the system of intrapartum care, relating to the deployment of midwives. <b>Design</b> Prospective semistructured observational study. <b>Setting</b> Labour wards of seven maternity units in the north west of England. <b>Participants</b> All midwives working on the labour ward during the observation period in 2000. <b>Main outcome measure</b> "Latent failures" within the system relating to midwifery staffing levels, deployment, and training or updating opportunities. <b>Results</b> Despite the exemplary dedication of midwives, potential risk of mishap due to their deployment occurred within the system of care. A shortfall of midwives existed in all seven maternity units and was most acute in the largest units. Six units relied on bank midwives to maintain minimum staffing levels. High risk practices (oxytocin administration and epidural blockades) continued during midwifery shortfalls in all units. Some adverse events and "near misses" were attributable to midwifery shortages in all units, and near misses remained unreported in all units. Uptake of opportunities for training or updating in interpretation of cardiotocographs and obstetric emergency management remained low owing to midwifery shortages in all units. A poor skill mix of midwives occurred at times in all units. In six units midwives spent time away from clinical areas performing clerical duties. In three units team midwifery systems were reported to erode labour ward skills and confidence. <b>Conclusion</b> Midwives are fundamental components in the system of intrapartum care, and the system cannot operate safely and effectively when the number of midwives is inadequate, midwives are poorly deployed, and they are unable to engage in opportunities for training and updating.
Carboplatin and Paclitaxel With vs Without Bevacizumab in Older Patients With Advanced Non–Small Cell Lung Cancer
Authors: Junya Zhu, Dhruv B. Sharma, Stacy W. Gray, Aileen B. Chen, Jane C. Weeks, Deborah Schrag
Journal: JAMA (2012)

A previous randomized trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in advanced non-small cell lung cancer (NSCLC). However, longer survival was not observed in the subgroup of patients aged 65 years or older.To examine whether adding bevacizumab to carboplatin and paclitaxel chemotherapy is associated with improved survival in older patients with NSCLC.Retrospective cohort study of 4168 Medicare beneficiaries aged 65 years or older with stage IIIB or stage IV non-squamous cell NSCLC diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region. Patients were categorized into 3 cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis: (1) diagnosis in 2006-2007 and bevacizumab-carboplatin-paclitaxel therapy; (2) diagnosis in 2006-2007 and carboplatin-paclitaxel therapy; or (3) diagnosis in 2002-2005 and carboplatin-paclitaxel therapy. The associations between carboplatin-paclitaxel with vs without bevacizumab and overall survival were compared using Cox proportional hazards models and propensity score analyses including information about patient characteristics recorded in SEER-Medicare.Overall survival measured from the first date of chemotherapy treatment until death or the censoring date of December 31, 2009.The median survival estimates were 9.7 (interquartile range [IQR], 4.4-18.6) months for bevacizumab-carboplatin-paclitaxel, 8.9 (IQR, 3.5-19.3) months for carboplatin-paclitaxel in 2006-2007, and 8.0 (IQR, 3.7-17.2) months for carboplatin-paclitaxel in 2002-2005. One-year survival probabilities were 39.6% (95% CI, 34.6%-45.4%) for bevacizumab-carboplatin-paclitaxel vs 40.1% (95% CI, 37.4%-43.0%) for carboplatin-paclitaxel in 2006-2007 and 35.6% (95% CI, 33.8%-37.5%) for carboplatin-paclitaxel in 2002-2005. Neither multivariable nor propensity score-adjusted Cox models demonstrated a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts. In propensity score-stratified models, the hazard ratio for overall survival for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel in 2006-2007 was 1.01 (95% CI, 0.89-1.16; P = .85) and compared with carboplatin-paclitaxel in 2002-2005 was 0.93 (95% CI, 0.83-1.06; P = .28). The propensity score-weighted model and propensity score-matching model similarly failed to demonstrate a statistically significant superiority for bevacizumab-carboplatin-paclitaxel. Subgroup and sensitivity analyses for key variables did not change these findings.Adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC.
Vα14 NK T cell–triggered IFN-γ production by Gr-1<b>+</b>CD11b<b>+</b> cells mediates early graft loss of syngeneic transplanted islets
Authors: Yohichi Yasunami, Satoshi Kojo, Hiroshi Kitamura, Atsushi Toyofuku, Masayuki Satoh, Masahiko Nakano, Kentaroh Nabeyama, Yoshiichiroh Nakamura, Nobuhide Matsuoka, Seiyo Ikeda, Masao Tanaka, Junko Ono, Naoki Nagata, Osamu Ohara, Masaru Taniguchi
Journal: The Journal of Experimental Medicine (2005)

Pancreatic islet transplantation is a highly promising approach for the treatment of insulin-dependent diabetes mellitus. However, the procedure remains experimental for several reasons, including its low efficiency caused by the early graft loss of transplanted islets. We demonstrate that Gr-1+CD11b+ cells generated by transplantation and their IFN-γ production triggered by Vα14 NKT cells are an essential component and a major cause of early graft loss of pancreatic islet transplants. Gr-1+CD11b+ cells from Vα14 NKT cell–deficient (Jα281−/−) mice failed to produce IFN-γ, resulting in efficient islet graft acceptance. Early graft loss was successfully prevented through the repeated administration of α-galactosylceramide, a specific ligand for Vα14 NKT cells, resulting in dramatically reduced IFN-γ production by Gr-1+CD11b+ cells, as well as Vα14 NKT cells. Our study elucidates, for the first time, the crucial role of Gr-1+CD11b+ cells and the IFN-γ they produce in islet graft rejection and suggests a novel approach to improving transplantation efficiency through the modulation of Vα14 NKT cell function.
Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS
Authors: Stefan Bittner, Tobias Ruck, Michael K Schuhmann, Alexander M Herrmann, Hamid Moha ou Maati, Nicole Bobak, Kerstin Göbel, Friederike Langhauser, David Stegner, Petra Ehling, Marc Borsotto, Hans-Christian Pape, Bernhard Nieswandt, Christoph Kleinschnitz, Catherine Heurteaux, Hans-Joachim Galla, Thomas Budde, Heinz Wiendl, Sven G Meuth
Journal: Nature Medicine (2013)
Diagnostic evaluation of paediatric pulmonary hypertension in current clinical practice
Authors: Maurice Beghetti, Rolf M.F. Berger, Ingram Schulze-Neick, Ronald W. Day, Tomás Pulido, Jeffrey Feinstein, Robyn J. Barst, Tilman Humpl
Journal: European Respiratory Journal (2013)

Current paediatric pulmonary hypertension (PH) diagnostic algorithms include some testing specifically for paediatrics, but it is unclear if this is used in clinical practice. We describe the current diagnostic workup of the TOPP (Tracking Outcomes and Practice in Paediatric Pulmonary hypertension) registry for suspected PH. We investigated 456 patients enrolled until February 2010. The majority had ECGs (94%), echocardiograms (96%) and/or chest radiographs (89%) performed and these were the noninvasive tests most frequently used for evaluation of suspected PH. No patient had all three tests considered normal, suggesting the potential for the combined use to rule out PH. For evaluation of complications associated with heart catheterisation (HC) we analysed a total of 908 HCs reported until February 2012. Of these, 554 were at diagnosis and 354 in follow-up. Complications were reported in 5.9% with five deaths considered related to HC, suggesting a higher rate of HC complications compared to adult studies. However, current recommendations support HC in paediatric PH. A proper application of the risk/benefit ratio for HC requires further data. Most children did not undergo the diagnostic workup currently recommended for adults, which highlights either incomplete awareness of current guidelines and/or challenges their appropriateness for children.
Impact of a nurse-led programme on comorbidity management and impact of a patient self-assessment of disease activity on the management of rheumatoid arthritis: results of a prospective, multicentre, randomised, controlled trial (COMEDRA)
Authors: Maxime Dougados, Martin Soubrier, Elodie Perrodeau, Laure Gossec, Françoise Fayet, Mélanie Gilson, Marie-Hélène Cerato, Sophie Pouplin, René-Marc Flipo, Laurent Chabrefy, Gael Mouterde, Liana Euller-Ziegler, Thierry Schaeverbeke, Bruno Fautrel, Alain Saraux, Isabelle Chary-Valckenaere, Gérard Chales, Emmanuelle Dernis, Pascal Richette, Xavier Mariette, Francis Berenbaum, Jean Sibilia, Philippe Ravaud
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Rheumatoid arthritis (RA) patients are at an increased risk of developing comorbid conditions. A close monitoring of the disease targeting a status of low disease activity is associated with a better outcome. The aim of this trial was to evaluate the impact of a nurse-led programme on comorbidities and the impact of patient self-assessment of disease activity on the management of RA. <h3>Methods</h3> We enrolled 970 patients (mean age 58 years, 79% women) in a prospective, randomised, controlled, open-label, 6-month trial. In the comorbidity group (n=482), the nurse checked comorbidities and sent the programme results to the attending physicians. In the self-assessment group (n=488), the nurse taught the patient how to calculate his/her Disease Activity Score which had to be reported on a booklet to be shared with the treating rheumatologist. The number of measures taken for comorbidities and the percentage of patients recording a change (initiation, switch or increased dose) in disease-modifying antirheumatic drugs (DMARDs) in the 6 months follow-up period of the study defined the outcomes of the trial. <h3>Results</h3> The number of measures taken per patient was statistically higher in the comorbidity group: 4.54±2.08 versus 2.65±1.57 (p&lt;0.001); incidence rate ratio: 1.78 (1.61–1.96) and DMARD therapy was changed more frequently in the self-assessment group: 17.2% versus 10.9% (OR=1.70 (1.17; 2.49), p=0.006). <h3>Conclusions</h3> This study demonstrates the short-term benefit of a nurse-led programme on RA comorbidity management and the impact of patient self-assessment of disease activity on RA treatment intensification. <h3>Trial registration number</h3> NCT #01315652.
Sensory and motor deficits exist on the non-injured side of patients with unilateral tendon pain and disability—implications for central nervous system involvement: a systematic review with meta-analysis
Authors: L J Heales, E C W Lim, P W Hodges, B Vicenzino
Journal: British Journal of Sports Medicine (2013)

Tendinopathy manifests as activity-related tendon pain with associated motor and sensory impairments. Tendon tissue changes in animals present in injured as well as contralateral non-injured tendon. This review investigated evidence for bilateral sensory and motor system involvement in unilateral tendinopathy in humans.A comprehensive search of electronic databases, and reference lists using keywords relating to bilateral outcomes in unilateral tendinopathy was undertaken. Study quality was rated with the Epidemiological Appraisal Instrument and meta-analyses carried out where appropriate. Analysis focused on comparison of measures in the non-symptomatic side of patients against pain-free controls.The search revealed 5791 studies, of which 20 were included (117 detailed reviews, 25 met criteria). There were 17 studies of lateral epicondylalgia (LE) and one each for patellar, Achilles and rotator cuff tendinopathy. Studies of LE were available for meta-analysis revealing the following weighted pooled mean deficits: pressure pain thresholds (-144.3 kPa; 95% CI -169.2 to -119.2 p<0.001), heat pain thresholds (-1.2°C; 95% CI -2.1 to -0.2, p<0.001), cold pain thresholds (3.1°C; 95% CI 1.8 to 4.4, p<0.001) and reaction time (37.8 ms; 95% CI 24.8 to 50.7, p<0.001).Deficits in sensory and motor systems present bilaterally in unilateral tendinopathy. This implies potential central nervous system involvement. This indicates that rehabilitation should consider the contralateral side of patients. Research of unilateral tendinopathy needs to consider comparison against pain-free controls in addition to the contralateral side to gain a complete understanding of sensory and motor features.
MicroRNA Silencing in Primates: Towards Development of Novel Therapeutics
Authors: Andreas Petri, Morten Lindow, Sakari Kauppinen
Journal: Cancer Research (2009)

Abstract MicroRNAs (miRNA) comprise an abundant class of small noncoding RNAs that act as important posttranscriptional regulators of gene expression. Accumulating evidence showing that aberrantly expressed miRNAs play important roles in human cancers underscores them as potential targets for therapeutic intervention. Recent reports on efficient miRNA silencing in rodents and nonhuman primates using high-affinity targeting by chemically modified antisense oligonucleotides highlight the utility of such compounds in the development of miRNA-based cancer therapeutics. [Cancer Res 2009;69(2):393–5]
Jump-starting tumor-specific T cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Vaccination with tumor antigens causes tumor regression in some melanoma patients despite negligible expansion of vaccine-specific T cells. Vaccination may instead result in the expansion of T cells specific for tumor antigens not contained in the vaccine, thus facilitating tumor regression, according to two articles from Pierre Coulie and colleagues on pages 241 and 249.






Figure 

Tumor-specific T cells (red) infiltrate a tumor after vaccination.




Tumor-specific T cells can be detected in the blood and the tumors of many melanoma patients, and yet these cells are unable to kill the tumor. What causes the impotence of these T cells is a mystery. Equally mysterious is why vaccination against tumor-specific antigens sometimes causes regression without expanding large numbers of vaccine-specific killer T cells.Pierre Coulie's group studied the specificity of antitumor T cell responses in patients vaccinated with a tumor antigen called MAGE-3. In one patient whose tumors regressed after vaccination, the authors found that T cells specific for nonvaccine tumor antigens became detectable or expanded from their prevaccine frequencies. Vaccine-specific T cells became detectable but remained at low frequency. Thus, reinvigoration of existing tumor-specific T cells and activation of new T cells after vaccination does not require large numbers of vaccine-specific T cells.

Although the mechanism underlying this phenomenon remains unknown, Coulie thinks that the few T cells stimulated by the vaccine may change the local environment of the tumor such that existing T cells can be reactivated and new T cells can be recruited.
Modern Treatment of Amyloidosis
Authors: Laura M. Dember
Journal: Journal of the American Society of Nephrology (2008)

During the past 10 to 15 years, there has been substantial progress in developing new treatments for the systemic amyloidoses. These advances have improved patient outcomes but have also raised new questions with direct clinical implications. For example, development of less intensive treatments for AL amyloidosis has made less certain the role of autologous stem cell transplantation, and new quantitative assays should now allow determination of the importance of fully eliminating amyloidogenic light chain production in AL disease. Additionally, observations from a clinical trial in AA amyloidosis have generated hypotheses about the relative contributions of amyloid precursors and mature fibrils to amyloidosis-associated kidney disease.
Serum periostin levels are correlated with progressive skin sclerosis in patients with systemic sclerosis
Authors: Y. Yamaguchi, J. Ono, M. Masuoka, S. Ohta, K. Izuhara, Z. Ikezawa, M. Aihara, K. Takahashi
Journal: British Journal of Dermatology (2012)

Periostin, a matricellular protein, serves as a regulator of wound healing and fibrosis. The role of periostin in the pathogenesis of systemic sclerosis (SSc) is unknown.To determine periostin levels in association with severity of skin fibrosis in patients with SSc.Expression of periostin was immunohistochemically examined in skin obtained from patients with SSc and healthy controls. Enzyme-linked immunosorbent assay was performed to evaluate serum periostin levels in association with clinical characteristics in 56 patients with SSc [diffuse cutaneous SSc (dSSc), n=16; and limited cutaneous SSc (lSSc), n=40] and 66 healthy controls.Periostin was strongly expressed in the affected dermis from patients with SSc. Periostin was colocalized in α-smooth muscle actin-positive myofibroblasts and platelet endothelial cell adhesion molecule-1-positive endothelial cells in SSc dermis. Serum levels of periostin in patients with dSSc were markedly elevated compared with those in patients with lSSc and control subjects. Patients with lSSc had increased periostin levels compared with healthy controls. In addition, significantly higher levels of periostin were observed in patients with dSSc with disease duration ≤5 years compared with those with disease duration >5 years. Furthermore, the modified Rodnan total skin thickness score (MRSS) was positively correlated with periostin levels in patients with SSc. Serial analysis revealed a correlation between periostin and MRSS; namely, MRSS decreased in line with decreased periostin levels in some patients with dSSc as the disease progressed.An elevated periostin level in patients with SSc is associated with severity of skin sclerosis. Periostin may be a potential biomarker for progressive skin fibrosis in SSc.