tbuckley/cabot-search huggingface dataset:
End-of-Life Decisions Among Cancer Patients Compared With Noncancer Patients in Flanders, Belgium
Authors: Lieve Van den Block, Johan Bilsen, Reginald Deschepper, Greta Van Der Kelen, Jan L. Bernheim, Luc Deliens
Journal: Journal of Clinical Oncology (2006)

Purpose Incidence studies reported more end-of-life decisions with possible/certain life-shortening effect (ELDs) among cancer patients than among noncancer patients. These studies did not correct for the different proportions of sudden/unexpected deaths of cancer versus noncancer patients, which could have biased the results. We investigated incidences and characteristics of ELDs among nonsudden cancer and noncancer deaths. Methods We sampled 5,005 certificates of all deaths in 2001 (Flanders, Belgium) stratified for ELD likelihood. Questionnaires were mailed to the certifying physicians. Data were corrected for stratification and nonresponse. Results The response rate was 59%. Among 2,128 nonsudden deaths included, ELDs occurred in 74% of cancer versus 50% of noncancer patients (P &lt; .001). Symptom alleviation with possible life-shortening effect occurred more frequently among cancer patients (P &lt; .001); nontreatment decisions occurred less frequently (P &lt; .001). The higher incidence of lethal drug use among cancer patients did not hold after correcting for patient age. Half of the cancer patients who died after an ELD were incompetent to make decisions compared with 76% of noncancer patients (P &lt; .001). Discussion with patients and relatives was similar in both groups. In one fifth of all patients the ELD was not discussed. Conclusion ELDs are common in nonsudden deaths. The different incidences for symptom alleviation with possible life-shortening effect and nontreatment decisions among cancer versus noncancer patients may be related to differences in dying trajectories and in timely recognition of patient needs. The end-of-life decision-making process is similar for both groups: consultation of patients and relatives can be improved in a significant minority of patients.
Lipid-Rich Atherosclerotic Plaques Detected by Gadofluorine-Enhanced In Vivo Magnetic Resonance Imaging
Authors: Marc Sirol, Vitalii V. Itskovich, Venkatesh Mani, Juan Gilberto S. Aguinaldo, John T. Fallon, Bernd Misselwitz, Hanns-Joachim Weinmann, Valentin Fuster, Jean-François Toussaint, Zahi A. Fayad
Journal: Circulation (2004)

MRI of specific components in atherosclerotic plaque may provide information on plaque stability and its potential to rupture. We evaluated gadofluorine in atherosclerotic rabbits using a new MR sequence that allows plaque detection within 1 hour after injection and assessed enhancement in lipid-rich and non-lipid-rich plaques.Twelve rabbits with aortic plaque and 6 controls underwent MRI before and up to 24 hours after gadofluorine injection (50 micromol/kg). Two T1-weighted, segmented gradient-echo sequences (TFL) were compared to enhance vessel wall delineation after injection: (1) an inversion-recovery prepulse (IR-TFL) or (2) a combination of inversion-recovery and diffusion-based flow suppression prepulses (IR-DIFF-TFL). With the use of IR-TFL at 1 hour after injection, the vessel wall was not delineated because of poor flow suppression; at 24 hours after injection, the enhancement was 37% (P<0.01). IR-DIFF-TFL showed significant enhancement after versus before contrast (1 hour: 164% [P<0.005]; 24 hours: 207% [P<0.001]). At 1 hour and 24 hours after injection, the contrast-to-noise ratio was higher with the use of IR-DIFF-TFL than with IR-TFL (1 hour: 13.0+/-7.7 versus -19.8+/-10.3 [P<0.001]; 24 hours: 15.2+/-5.9 versus 11.4+/-8.9, respectively [P=0.052]). There was no enhancement in the vessel wall after gadofluorine injection in the control group. A strong correlation was found (r2=0.87; P<0.001) between the lipid-rich areas in histological sections and signal intensity in corresponding MR images. This suggests a high affinity of gadofluorine for lipid-rich plaques.Gadofluorine-enhanced MRI improves atherosclerotic plaque detection. The IR-DIFF-TFL method allows early detection of atherosclerotic plaque within 1 hour after gadofluorine injection.
Clarifying the Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy
Authors: Leonard A. Levin
Journal: JAMA (1995)

Anterior ischemic optic neuropathy (AION), or optic nerve-head infarction, is the most common optic nerve disorder of the elderly except for glaucoma. There are two types of AION. The less common arteritic AION is associated with giant cell arteritis and was described more than 3000 years ago.<sup>1</sup>The pathophysiology of arteritic AION is well understood and consists of occlusion of the small posterior ciliary arteries supplying the anterior optic nerve. The diagnosis is suggested by the characteristic clinical findings of temporal ache or tenderness, polymyalgia rheumatica, and jaw claudication, as well as laboratory evidence of an elevated erythrocyte sedimentation rate. The diagnosis is proven by finding granulomatous inflammation with giant cells on biopsy of the temporal artery. Immediate high-dose corticosteroid therapy is mandatory, is usually effective prophylaxis for involvement of the other optic nerve, and may even reverse visual loss in occasional cases. See also p 625. In contrast,
Signaling capacity of the T cell antigen receptor is negatively regulated by the PTP1C tyrosine phosphatase.
Authors: G Pani, K D Fischer, I Mlinaric-Rascan, K A Siminovitch
Journal: The Journal of Experimental Medicine (1996)

The association of PTP1C deficiency with the multiplicity of lymphoid cell abnormalities manifested by motheaten (me) and viable motheaten (me(v)) mice suggests a pivotal role for this tyrosine phosphatase in the regulation of lymphocyte differentiation and function. To delineate the relevance of PTP1C to T cell physiology, we have examined me and me(v) T cells with regards to their capacity to transduce activating signals through the T cell antigen receptor (TCR). Although thymocyte maturation appeared normal in the mutant mice, both thymocytes and peripheral T cells from these animals exhibited proliferative response to TCR stimulation that were markedly increased relative to those elicited in normal cells. Compared to normal thymocytes, PTP1C-deficient thymocytes also showed increased constitutive tyrosine phosphorylation of the TCR complex and enhanced and prolonged TCR-induced tyrosine phosphorylation of the TCR-zeta and CD3-epsilon, as well as a number of cytosolic proteins, most notably a 38-kD phosphoprotein found to associate with the Grb2 adaptor SH2 domain in activated thymocytes. These latter phosphoproteins also associated with the Vav guanine nucleotide exchange factor upon TCR ligation, and were dephosphorylated by recombinant PTP1C in vitro. In conjunction with the finding of PTP1C-TCR association in unstimulated normal thymocytes, these results reveal the capacity of PTP1C to interact with and likely dephosphorylate resting and activated TCR complex components, as well as more distal signaling effectors that are normally recruited to the Vav and Grb2 SH2 domains after TCR stimulation. These data therefore strongly implicate PTP1C in the downregulation of TCR signaling capacity and, taken together with the aberrant prolongation of TCR-induced, mitogen-associated kinase (MAPK) activation observed in PTP1C-deficient thymocytes, these findings suggest that the inhibitory influence of PTP1C on TCR signal relay is realized through its effects on both the TCR complex and downstream signaling elements that couple the activated antigen receptor to the Ras/MAPK response pathway.
High Frequency of Somatic Frameshift BHD Gene Mutations in Birt-Hogg-Dubé–Associated Renal Tumors
Authors: Cathy D. Vocke, Youfeng Yang, Christian P. Pavlovich, Laura S. Schmidt, Michael L. Nickerson, Carlos A. Torres-Cabala, Maria J. Merino, McClellan M. Walther, Berton Zbar, W. Marston Linehan
Journal: JNCI Journal of the National Cancer Institute (2005)

The Birt-Hogg-Dubé (BHD) syndrome is an inherited genodermatosis characterized by a predisposition to hamartomatous skin lesions, pulmonary cysts, and renal carcinoma. Seventy-seven renal tumors from 12 patients with germline BHD mutations were examined by DNA sequencing to identify somatic mutations in the second copy of BHD. Sequence alterations were detected in the majority of renal tumors (41 of 77, 53%), with loss of heterozygosity at the BHD locus in a minority of additional tumors (14 of 77, 17%). The somatic mutations were distributed across the entire gene, and the majority resulted in frameshifts that are predicted to truncate the BHD protein. These results support a role for BHD as a tumor suppressor gene that predisposes to the development of renal tumors when both copies are inactivated.
Discordance Between HbA1c and Fructosamine
Authors: Robert M. Cohen, Yancey R. Holmes, Thomas C. Chenier, Clinton H. Joiner
Journal: Diabetes Care (2003)

OBJECTIVE—Discordances between HbA1c and other measures of glycemic control are common in clinical practice and remain unexplained. We developed a measure of discordance between HbA1c and fructosamine (FA) (glycosylated serum proteins) to conduct a systematic evaluation. We termed this the glycosylation gap (GG) and sought to determine its relationship to diabetic nephropathy. RESEARCH DESIGN AND METHODS—Measurements of HbA1c and FA on the same sample in 153 people were used to calculate GG, defined as the difference between measured HbA1c and HbA1c predicted from FA based on the population regression of HbA1c on FA. RESULTS—GG had a broad distribution (range, −3.2% to 5.5%); 40% of samples had values indicating major differences in prediction of complications risk by the measured versus predicted HbA1c. GG was highly correlated (r = 0.81) between measurements repeated in 65 patients 23 ± 2 weeks apart, indicating that the discordances are reliable and not explained by differences in turnover of underlying proteins. In 40 patients with type 1 diabetes of ≥15 years’ duration, an increase in GG by 1% was associated with a 2.9-fold greater frequency of increasing nephropathy stage (P = 0.0014). GG was −0.8 ± 0.2% in subjects with no nephropathy, −0.3 ± 0.2% with microalbuminuria/hypertension, and 0.7 ± 0.3% in subjects with proteinuria or renal dysfunction (P &amp;lt; 0.05). GG correlated better with nephropathy than did either HbA1c or FA alone in this population. CONCLUSIONS—The glycosylation gap may be a useful clinical research tool for evaluating physiologic sources of variation in diabetic complications beyond glycemic control.
Goblet cell carcinoid of the appendix.
Authors: K Park, K Blessing, K Kerr, U Chetty, H Gilmour
Journal: Gut (1990)

We have reviewed all cases of goblet cell carcinoid in the Department of Pathology, Edinburgh University. Of the 10 cases identified, two had died as a result of the tumour. This would suggest a poorer prognosis than is generally recognized. Those patients who subsequently had progression of their disease were not predicted by histological criteria. Because of the unpredictable behaviour of these tumours we recommend that such patients should correctly be treated by a right hemicolectomy.
Clinical relevance of TNM staging system according to breast cancer subtypes
Authors: Y.H. Park, S.J. Lee, E.Y. Cho, Y.La. Choi, J.E. Lee, S.J. Nam, J.-H. Yang, J.H. Shin, E.Y. Ko, B.-K. Han, J.S. Ahn, Y.-H. Im
Journal: Annals of Oncology (2011)
IMMUNOLOGICAL REACTIONS BETWEEN DEXTRAN POLYSACCHARIDE AND SOME BACTERIAL ANTISERA
Authors: José Zozaya
Journal: The Journal of Experimental Medicine (1932)

Dextran, the synthetic polysaccharide produced by Leuconostoc mesenterioides from saccharose, reacts immunologically with antisera from pneumococci, some of the Sahnonella and some of the types of Streptococcus viridans (Bargen). This immunological relationship is independent of the specific antipolysaccharide antibodies of these sera, suggesting the existence of a distinct antibody produced by an active group of the specific bacterial polysaccharide, which is similar or identical to the active group of the dextran polysaccharide.
A computer system for processing data from routine pulmonary function tests.
Authors: A I Pack, R McCusker, F Moran
Journal: Thorax (1977)

In larger pulmonary function laboratories there is a need for computerised techniques of data processing. A flexible computer system, which is used routinely, is described. The system processes data from a relatively large range of tests. Two types of output are produced--one for laboratory purposes, and one for return to the referring physician. The system adds an automatic interpretative report for each set of results. In developing the interpretative system it has been necessary to utilise a number of arbitrary definitions. The present terminology for reporting pulmonary function tests has limitations. The computer interpretation system affords the opportunity to take account of known interaction between measurements of function and different pathological states.
Current Status of Developments and Applications of Micro-CT
Authors: Erik L. Ritman
Journal: Annual Review of Biomedical Engineering (2011)

Use of microscopic computed-tomography (micro-CT) scanning continues to grow in biomedical research. Laboratory-based micro-CT scanners, laboratory-based nano-CT scanners, and integrated micro-CT/SPECT and micro-CT/PET scanners are now manufactured for “turn-key” operation by a number of commercial vendors. In recent years a number of technical developments in X-ray sources and X-ray imaging arrays have broadened the utility of micro-CT. Of particular interest are photon-counting and energy-resolving detector arrays. These are being explored to maximize micro-CT image grayscale dynamic range and to further increase image contrast by utilizing the unique spectral attenuation characteristics of individual chemical elements. X-ray phase-shift images may increase contrast resolution and reduce radiation exposure. Although radiation exposure is becoming a concern with the drive for increased spatial and temporal resolution, especially for longitudinal studies, gated scans and limited scan-data-set reconstruction algorithms show great potential for keeping radiation exposure to a minimum.
What Is Different About the Market for Health Care?
Authors: David A Wells, Joseph S Ross, Allan S Detsky
Journal: JAMA (2007)

ECONOMICS IS A SOCIAL SCIENCE THAT DESCRIBES HOW society produces and consumes goods and services. It is concerned with both efficiency (getting the most out of a fixed amount of resources) and distribution (who gains and who loses). The use of free markets as a mechanism of promoting efficiency has been touted by the majority of economists since the time of Adam Smith. His theory was that in free markets each individual, pursuing his or her own self-interests, will be led, as if by some “invisible hand,” to produce an allocation that maximizes society’s utility. However, certain conditions are required for free markets to result in efficient allocations. First among these is perfect competition, ie, a market in which no individual buyer or seller can affect the price by his or her actions. Without this condition, structural imperfections or market distortions arise and result in inefficient allocations. For example, the oil market is distorted because the Organization of the Petroleum Exporting Countries (OPEC) has exerted influence on the price of oil by restricting its supply since the 1970s. The market for health care contains many distortions, including asymmetry of information between clinicians and patients; clinicians’ dual roles as patient agent and independent business owner (profiting by ordering or providing certain medical services); the effect of insurance in reducing the apparent cost of health care services to patients (since the full cost of health care is not charged to patients, also known as the “price-wedge” distortion); tax subsidies that have a similar effect on consumers’ decisions to purchase insurance; and monopoly power bestowed on certain professions and, in some countries, health insurance plans, thereby limiting competition. Over the last 40 years, health economists have devoted considerable attention to the impact of these distortions on the market for health care. Feldstein was one of the first to write about the distorting effect of health insurance tax subsidies on market efficiency. Detsky described asymmetry of information and impact of clinician as agent. Arrow noted that when markets fail, public policies are often derived to ameliorate the consequences. In this Commentary we review 3 classic efforts to describe, to quantify, and to propose solutions to market distortions in health care. These efforts framed policy initiatives over the last 40 years and remain relevant to health policy debates today.
Imprinting of the Gsα gene GNAS1 in the pathogenesis of acromegaly
Authors: Bruce E. Hayward, Anne Barlier, Márta Korbonits, Ashley B. Grossman, Philippe Jacquet, Alain Enjalbert, David T. Bonthron
Journal: Journal of Clinical Investigation (2001)

Approximately 40% of growth hormone–secreting pituitary adenomas have somatic mutations in the GNAS1 gene (the so-called gsp oncogene). These mutations at codon 201 or codon 227 constitutively activate the α subunit of the adenylate cyclase–stimulating G protein Gs. GNAS1 is subject to a complex pattern of genomic imprinting, its various promoters directing the production of maternally, paternally, and biallelically derived gene products. Transcripts encoding Gsα are biallelically derived in most human tissues. Despite this, we show here that in 21 out of 22 gsp-positive somatotroph adenomas, the mutation had occurred on the maternal allele. To investigate the reason for this allelic bias, we also analyzed GNAS1 imprinting in the normal adult pituitary and found that Gsα is monoallelically expressed from the maternal allele in this tissue. We further show that this monoallelic expression of Gsα is frequently relaxed in somatotroph tumors, both in those that have gsp mutations and in those that do not. These findings imply a possible role for loss of Gsα imprinting during pituitary somatotroph tumorigenesis and also suggest that Gsα imprinting is regulated separately from that of the other GNAS1 products, NESP55 and XLαs, imprinting of which is retained in these tumors.
Experimental ASD closure using autologous cell-seeded interventional closure devices
Authors: C Jux
Journal: Cardiovascular Research (2002)

Objective: Atrial septal defect (ASD) occluders are permanent implants in paediatric cardiology which serve as mechanical shields until complete overgrowth and incorporation of the occluding device by autologous tissue has occurred. Thereafter, the foreign body material making up the device is dispensable and bears potential long-term adverse effects. Rapid, firm and complete incorporation into the atrial septal wall should be a prerequisite for biodegradable devices. In this study, the feasibility of using autologous cell-seeded devices was investigated by (a) testing the influence of a collagen coating on cellular stress resistance in vitro and (b) comparing the short-term effects between cell-seeded, collagen-coated and acellular ASD occluders in vivo. Methods: Native and collagen-coated Dacon fabrics and Starflex-devices were pre-seeded with autologous fibroblasts (skin biopsy) and evaluated using various mechanical stress tests. In a sheep model interventionally created ASDs were closed using either autologous pre-seeded or conventional (acellular) Starflex-devices. Results: ASD closure devices were successfully pre-seeded with autologous cells. The incubation period needed, the cellular density achieved and the mechanical stability of the cytolayer after mechanical stressing (implantation) were improved by applying a collagen matrix on the fabric. Compared to the thin layer of ingrown tissue seen on conventional occluders after 30 days in vivo, a thicker layer of organising, newly formed granulation tissue on pre-seeded collagen-coated devices embedded not only the Dacron fabric, but also completely covered the spring arms of the device underneath a layer of neo-endothelium. Conclusion: Autologous cell pre-seeding of interventional closure devices is feasible since the cells survive the mechanical stress encountered during implantation. Rapid, firm and complete ingrowth of occluder devices into a thicker layer of young fibrous granulation tissue can be achieved, but an increased thrombogenicity currently limits the in vivo application.
Cytokine-Induced Mobilization of Circulating Endothelial Progenitor Cells Enhances Repair of Injured Arteries
Authors: Deling Kong, Luis G. Melo, Massimiliano Gnecchi, Lunan Zhang, Gustavo Mostoslavsky, Chong C. Liew, Richard E. Pratt, Victor J. Dzau
Journal: Circulation (2004)

The existence of circulating endothelial progenitor cells (CEPCs) has previously been documented. These cells can be mobilized by cytokines and are recruited to sites of injury, where they may participate in tissue repair. In the present study, we examined the hypothesis that mobilization of CEPCs by exogenous granulocyte-colony stimulating factor (G-CSF) enhances repair of injured arteries by facilitating reendothelialization and inhibiting neointima development.Male rats were injected daily with 50 microg/kg recombinant human G-CSF or 0.9% NaCl SC for 8 days. On the fifth day of treatment, 1 mL of blood was collected for fluorescence-activated cell sorting analysis of mononuclear cells, and the animals underwent balloon angioplasty of the common carotid artery. The animals were killed at 2 or 4 weeks after injury, and the carotid arteries were harvested and processed for immunohistochemistry, scanning electron microscopy (SEM), and morphometric analysis of endothelialization and neointimal formation. G-CSF increased the number of circulating mononuclear cells that express endothelial cell lineage markers several-fold. SEM and immunohistochemical staining with the endothelial marker, platelet and endothelial cell adhesion molecule-1, showed rapid and nearly complete (>90%) reendothelialization of the denuded vessels in the G-CSF-treated animals compared with <20% in the control animals. Reendothelialization was paralleled by a decrease in inflammation in the vessel wall. Neointima thickness was reduced by approximately 60% in the G-CSF-treated animals compared with control animals at 2 and 4 weeks after injury.We postulate that cytokine-induced mobilization of CEPCs may be a suitable therapeutic strategy for prevention of restenosis after revascularization procedures.