tbuckley/cabot-search huggingface dataset:
The Dilemmas of Managed Care
Authors: Lucy Johns
Journal: JAMA (1997)

To the Editor.  —The lucid analysis by Dr Mechanic 1 of the dilemmas presented by managed care neglects one attribute of the health sector that is unchanged by this new approach: the tendency toward revenue maximization by the physician. 2 With fee-for-service, this tendency was shrouded from patients because it coincided with their receiving all possible care. Now, as profit-seeking health plans erode public trust, plans can divert consumer dissatisfaction back toward the physician by eliminating gag rules and broadening the prevalence of global capitation. Gag rules then will mutate to self-censorship, while needed care may continue to be withheld. The provider service networks contemplated for Medicare patients will be rife with the same tension.  For better or worse, entrepreneurship in the delivery of health care, whether by professionals or by corporate America, affects the physician-patient relationship. Managed care has not solved the problem of paying the physician in the
Does leptin play a cytokine-like role within the airways of COPD patients?
Authors: A. Bruno, P. Chanez, G. Chiappara, L. Siena, S. Giammanco, M. Gjomarkaj, G. Bonsignore, J. Bousquet, A. M. Vignola
Journal: European Respiratory Journal (2005)

The leptin-leptin receptor system might be up-regulated in the airways of chronic obstructive pulmonary disease (COPD). In bronchial biopsies obtained from normal subjects and smokers, with and without COPD, the present study examined leptin and leptin-receptor expression and their co-localisation in airway and inflammatory cells. Combining immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick end-labelling techniques, apoptosis in airway and inflammatory cells and in leptin and leptin-receptor expressing cells was investigated. In the epithelial cells both leptin and leptin-receptor expression was higher in normal subjects than in smokers and COPD subjects. By contrast, in the sub-mucosa, leptin was over-expressed in COPD when compared with normal subjects and smokers. Leptin and its receptor were co-localised, mainly with activated T cells (CD45R0) and CD8 + T lymphocytes. In smokers, apoptosis was found in some inflammatory cells, whereas in COPD inflammatory cells, leptin and leptin-receptor positive cells were not apoptotic. Leptin expression was related to COPD severity and assessed using the Global initiative for Chronic Obstructive Lung Disease classification. In conclusion, the present study shows an increased leptin expression in bronchial mucosa of chronic obstructive pulmonary disease patients, associated with airway inflammation and airflow obstruction.
Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
Authors: Sophie Péron, Ayse Metin, Pauline Gardès, Marie-Alexandra Alyanakian, Eamonn Sheridan, Christian Peter Kratz, Alain Fischer, Anne Durandy
Journal: The Journal of Experimental Medicine (2008)

Immunoglobulin (Ig) class switch recombination (CSR) deficiencies are rare primary immunodeficiencies characterized by the lack of switched isotype (IgG/IgA/IgE) production. In some cases, CSR deficiencies can be associated with abnormal somatic hypermutation. Analysis of CSR deficiencies has helped reveal the key functions of CSR-triggering molecules, i.e., CD40L, CD40, and effector molecules such as activation-induced cytidine deaminase and uracil N-glycosylase. We report a new form of B cell-intrinsic CSR deficiency found in three patients with deleterious, homozygous mutations in the gene encoding the PMS2 component of the mismatch repair machinery. CSR was found partially defective in vivo and markedly impaired in vitro. It is characterized by the defective occurrence of double-strand DNA breaks (DSBs) in switch regions and abnormal formation of switch junctions. This observation strongly suggests a role for PMS2 in CSR-induced DSB generation.
Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial
Authors: Frank Smithuis, Moe Kyaw Kyaw, Ohn Phe, Thein Win, Pyay Phyo Aung, Aung Pyay Phyo Oo, Arkar Linn Naing, Mya Yee Nyo, Naing Zaw Htun Myint, Mallika Imwong, Elizabeth Ashley, Sue J Lee, Nicholas J White
Journal: The Lancet Infectious Diseases (2010)
Cross-linked type I and type II collagenous matrices for the repair of full-thickness articular cartilage defects—A study in rabbits
Authors: Pieter Buma, Jeroen S. Pieper, Tony van Tienen, Job L.C. van Susante, Peter M. van der Kraan, Jacques H. Veerkamp, Wim B. van den Berg, Rene P.H. Veth, Toin H. van Kuppevelt
Journal: Biomaterials (2003)
Necessary Collusion: Prognostic Communication With Advanced Cancer Patients
Authors: Paul R. Helft
Journal: Journal of Clinical Oncology (2005)

As a young oncologist, I find myself wrestling with many of the most difficult issues in the practice of oncology: making difficult trade-offs between risk and benefits of arduous treatments, finding sources of strength to deal with the devastating realities of patients’ situations, and determining how to communicate important information to patients in ways that give them honest and useful information, but still allow them to preserve some hope for the future. It is this last issue on which I offer my thoughts here. I have noticed that although common wisdom holds that we should give accurate and honest prognostic information to patients at all times, in practice this is hard to do. So, I find myself engaging in a process of communication about prognosis with patients which, in a sense, allows the cold, hard facts to come out over time, as opposed to presenting them up front. I have found other oncologists who seem to use a similar strategy. I do this because it is a style of communication which, I think, “works” for me and my patients: patients come to deal with the painful knowledge of their ultimate outcomes over time in ways that I think allow them to cope along the way. But I have continuously asked myself whether this is the “right” way to communicate. Is such a strategy of communication ethical? Looking to the literature about prognostic communication with patients with advanced cancer, two lines of thought dominate. The first suggests that patients want accurate estimates of their prognosis and that accurate estimates benefit patients by allowing them to make end-of-life plans consistent with their values. The second suggests that patients desire, above all, to maintain hope for their situations, and that the “management of hope” permits the prognosticating oncologist to take some liberties with prognostic estimates in order to preserve the patient’s ability to maintain hope. These two lines of thinking appear to be at odds with one another. Is there, however, an ethical way of resolving the tensions between these two views? In the end, I believe that except in instances where stark frankness is openly requested, a style of communication that allows patients to dictate most of the flow of prognostic information or to avoid it is an ethical strategy of prognostic communication. I will refer to this strategy as “necessary collusion.” By collusion I mean the spoken or unspoken agreement we sometimes enter into with some patients to avoid or delay discussing a definitive, numerical prognostic estimate of life expectancy. This article is an examination of whether such collusion is ethical. I am going to argue that such collusion can be ethical, because of certain special characteristics of the situation of patients with advanced cancer and their relationships with their oncologists.
Detection and Grading of Soft Tissue Sarcomas of the Extremities with 18F-3′-Fluoro-3′-Deoxy-<scp>l</scp>-Thymidine
Authors: David C. P. Cobben, Philip H. Elsinga, Albert J. H. Suurmeijer, Wim Vaalburg, Bram Maas, Piet L. Jager, Harald J. Hoekstra
Journal: Clinical Cancer Research (2004)

The aim of the study was to investigate the feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine positron emission tomography (FLT-PET) for the detection and grading of soft tissue sarcoma (STS).Nineteen patients with 20 STSs of the extremities were scanned, using attenuation corrected whole-body FLT-PET. Standardized uptake values (SUVs) and tumor:nontumor ratios (TNTs) were compared with histopathological parameters using French and Japanese grading systems.Mean SUV, maximal SUV, and TNT could differentiate between low-grade (grade 1; n = 6) STS and high-grade (grade 2 and 3; n = 14) STS according to the French grading system (P = 0.001). Mean SUV, max SUV, and TNT correlated with mitotic score, MIB-1 score, the French and Japanese grading system (* = 0.550-0.747).FLT-PET is able to visualize STS and differentiate between low-grade and high-grade STS. The uptake of FLT correlates with the proliferation of STS.
Dietary Regulation of Intestinal Gene Expression
Authors: I. R. Sanderson, S. Naik
Journal: Annual Review of Nutrition (2000)

We are becoming increasingly aware of inherited genetic abnormalities as causes of disease. However, alterations in gene expression can also contribute to other disease processes. Recently it has been suggested that our environment may alter such genes and thus be a direct influence on disease. Diet is a potent mechanism for altering the environment of cells of most organs, particularly the gastrointestinal tract. This review addresses the influence of nutritional factors on intestinal gene regulation. These influences include insulin, which is not a dietary component but responds to dietary changes, and butyrate, a short chain fatty acid produced by normal intestinal flora. Manipulation of diet may be a means of treating intestinal disorders. Nutritional treatment therefore is also discussed in the light of its effect on gene expression.
Antioxidants and cardiovascular disease; panaceas or tonics for tired sheep?
Authors: Francesco Visioli, John F. Keaney, Barry Halliwell
Journal: Cardiovascular Research (2000)

There is now a large body of population studies showing that diets high in fruits and vegetables, i.e. foods rich in antioxidant compounds, are associated with a lower incidence of cardiovascular disease [1]; moreover, many in vitro and some in vivo studies have suggested that oxidative modification of low density lipoprotein is involved in the onset of atherosclerosis and exacerbates its clinical manifestations [2] … 

* Corresponding author
MicroRNA Profiling of Sporadic and Hereditary Medullary Thyroid Cancer Identifies Predictors of Nodal Metastasis, Prognosis, and Potential Therapeutic Targets
Authors: Deepak Abraham, Nicole Jackson, Justin S. Gundara, JingTing Zhao, Anthony J. Gill, Leigh Delbridge, Bruce G. Robinson, Stan B. Sidhu
Journal: Clinical Cancer Research (2011)

While the molecular basis of hereditary medullary thyroid cancer (HMTC) has been well defined, little is known about the molecular pathogenesis of sporadic medullary thyroid cancer (SMTC). In addition, microRNAs (miRNAs) have been shown to be important diagnostic and prognostic markers in cancer but have not been defined in MTC. Our aim was to study the miRNA profile of MTC to identify prognostic biomarkers and potential therapeutic targets.MiRNA microarray profiling was carried out in fresh frozen tissues from patients with SMTC (n = 12) and HMTC (n = 7). Differential expression of three miRNAs was confirmed in a validation cohort of SMTC and HMTC samples (n = 45) using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. The functional role of a selected miRNA was investigated in vitro in the human medullary thyroid carcinoma cell line (TT cells) using cell proliferation assays and Western blotting analysis.MiRs-183 and 375 were overexpressed (P = 0.001; 0.031) and miR-9* was under-expressed (P = 0.011) in SMTC versus HMTC. Overexpression of miRs-183 and 375 in MTC predicted lateral lymph node metastases (P < 0.001; P = 0.001) and was associated with residual disease (P = 0.001; 0.003), distant metastases (P = 0.003; 0.001), and mortality (P = 0.01; 0.011). Knock down of miR-183 expression in the TT cell line induced a significant decrease in the viable cell count and upregulation of the protein LC3B, which is associated with autophagy.Our data indicate that miRNAs play a pivotal role in the biology of MTC and represent an important class of prognostic biomarkers and therapeutic targets warranting further investigation.
Interleukin-18 and the Risk of Coronary Heart Disease in European Men
Authors: Stefan Blankenberg, Gérald Luc, Pierre Ducimetière, Dominique Arveiler, Jean Ferrières, Philippe Amouyel, Alun Evans, François Cambien, Laurence Tiret
Journal: Circulation (2003)

Background— Interleukin (IL)-18 promotes atherosclerotic plaque growth and vulnerability. It is unknown, however, whether elevations of circulating IL-18 precede the onset of coronary events in apparently healthy individuals. Methods and Results— We evaluated the relationship between baseline plasma levels of IL-18 and the subsequent incidence of coronary events over a 5-year follow-up in the Prospective Epidemiological Study of Myocardial Infarction (PRIME),which included 10 600 healthy European men aged 50 to 59 years at baseline. Analysis was performed in a nested case-control manner comparing 335 cases with a coronary event to 670 age-matched controls. Baseline levels of IL-18 were significantly higher in men who developed a coronary event than in controls (225.1 versus 203.9 pg/mL, P =0.005). After adjustment for most potential confounders, including C-reactive protein, IL-6, and fibrinogen, the relative risk of future coronary events associated with increasing tertiles of IL-18 was 1.65 (95% CI 1.14 to 2.40, P =0.008) in Northern Ireland, 1.29 (95% CI 0.96 to 1.73, P =0.09) in France, and 1.42 (95% CI 1.13 to 1.79, P =0.003) in both populations combined ( P =0.31 for the test of homogeneity between populations). In all models, IL-18 made an independent contribution to the prediction of risk over lipids or other inflammatory markers such as C-reactive protein, IL-6, or fibrinogen. Conclusions— Plasma IL-18 level was identified as an independent predictor of coronary events in healthy, middle-aged European men. Determination of circulating IL-18 might improve the prediction of coronary events.
CPAP titration by an auto-CPAP device based on snoring detection: a clinical trial and economic considerations
Authors: M Berkani, F Lofaso, C Chouaid, M Pia d'Ortho, D Theret, V Grillier-Lanoir, A Harf, B Housset
Journal: European Respiratory Journal (1998)

This study aimed to assess the ability of an auto-nasal continuous positive airway pressure (nCPAP) device (REM + auto; NPBFD, Nancy, France) to predict the optimal constant nCPAP level. The apnoea/hypopnoea detection facility of the auto-nCPAP device was deliberately disabled and nasal mask pressure vibration detection was the only mode of pressure setting. The auto-nCPAP device was tested on 10 previously untreated patients with obstructive sleep apnoea during a single night, with ambulatory polysomnography performed in a conventional hospital room; the efficacy of the fixed pressure determined by the auto-nCPAP device was assessed by an ambulatory full polysomnography 2 weeks after the initiation of treatment at home. The fixed nCPAP pressure was effective (apnoea/hypopnoea and arousal indices &lt;10 events x h(-1)) in all but two of the 10 patients studied. When the fixed nCPAP pressure was increased by 2 cmH2O in these two patients, sleep and respiration were normalized. Since only 12 ambulatory polysomnographic recordings were used to determine the effective nasal continuous positive airway pressure level, and as the device restored normal breathing and sleep in all 10 patients, it was concluded that this method of nasal continuous positive airway pressure titration may improve cost-effectiveness and reduce waiting lists in sleep laboratories.
THE PRACTICE OF THE TOTAL PUSH METHOD IN THE TREATMENT OF CHRONIC SCHIZOPHRENIA
Authors: Kenneth J. Tillotson
Journal: American Journal of Psychiatry (1939)

The foregoing group of 11 deteriorated patients, suffering from chronic schizophrenia, who have been ill an average of 12.1 years and whose average hospitalization is over ten years, have shown the changes as recorded after three months' treatment with the total push method. The larger group of 22 patients in a shorter period of time are making similar improvement in their social conduct and general reaction. They can be described as slightly improved, much improved and markedly improved. In none of these patients has the condition become worse. This improvement is shown in better contact with reality, in social responsiveness, increased activities, skill and coordination, sociability, improved mood and æstheticism with some degree of improvement in physical status. There has been a response to competitive games and to the reward-punishment and praise-blame concepts in accordance with the theories and principles advanced by Dr. Myerson. One of our patients, Patient 2, has improved to such an extent in his social status that a program of re-education has begun and he is already making satisfactory progress. It is our hope that such a program of re-education and an increasing program of psychotherapy may be applied to a considerable number of these patients. We believe that if the insulin and metrazol therapy are used, the total push method should be instituted in its fullest sense as an important adjunct. We are offering it, however, as a distinct method of organized, intensive, individual activation in chronic schizophrenia. Such an intensive method of treatment has not only improved the mental and physical status of these patients, but since its success depends upon the thoroughly coordinated efforts of nurses, physicians, physiotherapists, physical instructors and occupational therapists, it has been stimulating to the entire personnel and has added much to the hospital morale.
Incidence and Preventability of Adverse Drug Events Among Older Persons in the Ambulatory Setting
Authors: Jerry H. Gurwitz, Terry S. Field, Leslie R. Harrold, Jeffrey Rothschild, Kristin Debellis, Andrew C. Seger, Cynthia Cadoret, Leslie S. Fish, Lawrence Garber, Michael Kelleher, David W. Bates
Journal: JAMA (2003)

<h3>Context</h3> Adverse drug events, especially those that may be preventable, are among the most serious concerns about medication use in older persons cared for in the ambulatory clinical setting. <h3>Objective</h3> To assess the incidence and preventability of adverse drug events among older persons in the ambulatory clinical setting. <h3>Design, Setting, and Patients</h3> Cohort study of all Medicare enrollees (30 397 person-years of observation) cared for by a multispecialty group practice during a 12-month study period (July 1, 1999, through June 30, 2000), in which possible drug-related incidents occurring in the ambulatory clinical setting were detected using multiple methods, including reports from health care providers; review of hospital discharge summaries; review of emergency department notes; computer-generated signals; automated free-text review of electronic clinic notes; and review of administrative incident reports concerning medication errors. <h3>Main Outcome Measures</h3> Number of adverse drug events, severity of the events (classified as significant, serious, life-threatening, or fatal), and whether the events were preventable. <h3>Results</h3> There were 1523 identified adverse drug events, of which 27.6% (421) were considered preventable. The overall rate of adverse drug events was 50.1 per 1000 person-years, with a rate of 13.8 preventable adverse drug events per 1000 person-years. Of the adverse drug events, 578 (38.0%) were categorized as serious, life-threatening, or fatal; 244 (42.2%) of these more severe events were deemed preventable compared with 177 (18.7%) of the 945 significant adverse drug events. Errors associated with preventable adverse drug events occurred most often at the stages of prescribing (n = 246, 58.4%) and monitoring (n = 256, 60.8%), and errors involving patient adherence (n = 89, 21.1%) also were common. Cardiovascular medications (24.5%), followed by diuretics (22.1%), nonopioid analgesics (15.4%), hypoglycemics (10.9%), and anticoagulants (10.2%) were the most common medication categories associated with preventable adverse drug events. Electrolyte/renal (26.6%), gastrointestinal tract (21.1%), hemorrhagic (15.9%), metabolic/endocrine (13.8%), and neuropsychiatric (8.6%) events were the most common types of preventable adverse drug events. <h3>Conclusions</h3> Adverse drug events are common and often preventable among older persons in the ambulatory clinical setting. More serious adverse drug events are more likely to be preventable. Prevention strategies should target the prescribing and monitoring stages of pharmaceutical care. Interventions focused on improving patient adherence with prescribed regimens and monitoring of prescribed medications also may be beneficial.
Rituximab therapy in autoimmune pulmonary alveolar proteinosis
Authors: R. Borie, M-P. Debray, C. Laine, M. Aubier, B. Crestani
Journal: European Respiratory Journal (2009)

Idiopathic pulmonary alveolar proteinosis is presumed to be an autoimmune disorder that may lead to pulmonary insufficiency. However, steroids do not appear to be effective and the standard of therapy is whole-lung lavage. We report the first case of successful therapy with rituximab, which addresses the pathogenic mechanism of pulmonary alveolar proteinosis.
Draining Lymph Nodes of Corneal Transplant Hosts Exhibit Evidence for Donor Major Histocompatibility Complex (MHC) Class II–positive Dendritic Cells Derived from MHC Class II–negative Grafts
Authors: Ying Liu, Pedram Hamrah, Qiang Zhang, Andrew W. Taylor, M. Reza Dana
Journal: The Journal of Experimental Medicine (2002)

To examine the widely accepted dogmas that corneal grafts lack passenger leukocytes or cells capable of migrating directly to lymph nodes (LNs), we tracked the migration of corneal graft-derived transgenic green fluorescent protein (GFP; Iab) cells into the draining LNs of allogeneic (Iad) recipients. GFP+ cells were identified in cervical LNs several hours after transplantation, and this traffic was significantly enhanced when grafts were placed in inflamed recipient beds. Draining cells were Iab+, CD45+, and CD11c+, and examination of ungrafted corneas revealed numerous similarly CD45+CD11c+CD3−CD8α− cells that uniformly lacked major histocompatibility complex (MHC) class II expression; transmission electron microscopy confirmed the presence of morphologically similar cells. After transplantation, or placement in culture, these CD11c+ cells became class II+ in a time-dependent manner and were capable of allostimulatory function. However, the stimulatory capacity of these cornea-derived dendritic cells (DCs) was suppressed compared with splenic controls. These results demonstrate for the first time that the cornea is endowed with resident DCs that are universally MHC class II− but that are capable of expressing class II antigen after surgery and migrating to draining LNs of allografted hosts. These data refute the tenet that the cornea is immune privileged due to lack of resident lymphoreticular cells or due to antigenic sequestration from systemic immunity.