tbuckley/cabot-search huggingface dataset:
Abstract P1-04-09: Extended characterization and target analysis of circulating epithelial cells in early and late breast cancer
Authors: L Habets, F Bettina, I El-Ghali, W Körber, M Danaei, M Kusche, K Pachmann
Journal: Cancer Research (2013)

Abstract The MAINTRAC based (RBC lysis immunofluoretic detection and analysis on the Olympus ScanR system) finds more cells compared to enrichment based systems. The relative cheapness and low amounts of blood (1ml) allows frequent monitoring during early and late disease therapy steps. The clinical relevance of rising or falling counts of living (EPCAM+CD45negDAPIneg) CEC has been demonstrated in early and late disease by Pachmann. In addition we could show that these cells express stem cell, EMT and hypoxia markers. To our surprise we found high counts of this cell type in 90% of patients with fatty liver disease (NAFLD) in a non healthy non malignant control population. In a healthy control population in only 2% very few cells were found. Our conclusion so far CEC are a phenomenon driven by a hypoxic hyperacidic tissue situation shared by malignant and non malignant disease. The detectable cell population showed considerable morphologic heterogeneity urging us to introduce extended characterization and more comprehensive analysis. We therefore slightly adapted the basic MAINTRAC procedure to allow four color flowcytometric detection and analysis on the Amnis (EMD-Millipore) FlowSight device. The basic panel consists of (CD45PE, DAPI- blue, ALDH-FITC and EPCAMAF660). Extended Characterization is possible with different other panels including (HIF1, betacatenin, several pan- and single cytokeratins and CD44/CD24) and targets like ER, HER2, PDL-1 (immune checkpoint target) and phosphatidylserine. With this new approach we examined so far 66 patients with early and 53 patients with late disease. In early disease we found living CEC in 32 of 66 cases, with cell counts from 200 to 21642 per ml. In late disease in 27of 53 cases, cell counts varying from 481 to 97339 cells per ml. The percentage of living CEC varied from 0 to 60%. In all cases we found PDL-1 and ALDH1 expressed nearly exclusively on EPCAM+ cells demonstrating their suitability as a CEC specific marker. In cases with early relapse and rapid progression only few or none CEC are found especially in triple negative and HER2+ER negative cases. In these situations we find however EPCAM negative cell clusters. The IDEAS software allows comprehensive analysis of all visible phenomena including single cells, cell aggregates and exosomes. So far we still see no differences between “real” tumor derived CEC and “false positive” liver derived CEC. There is however preliminary evidence that CK20+ cells counts are much higher than EPCAM +counts in real compared with liver caused disease. A conclusive picture of these intruiging phenomena is not possible it seems however that the chosen way of extended characterization including new issues like cell clusters and exosomes should lead to a further elucidation of this biology and the use of CEC as a reliable “fluid biopsy”. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-04-09.
Pulmonary Alveolar Proteinosis — Is Host Defense Awry?
Authors: Claire M. Doerschuk
Journal: New England Journal of Medicine (2007)

Pulmonary alveolar proteinosis is a rare disorder caused by abundant accumulation of surfactant-derived components in the lungs. The incidence is estimated to be 0.36 case per million population, and the prevalence, 3.70 cases per million.1 About 500 cases have been recorded in the literature.The condition usually presents as progressive dyspnea and a minimally productive cough. There are elevated serum levels of products derived from pulmonary epithelial cells, including cytokeratin 19, the mucin KL-6, and surfactant proteins A, B, and D. Pulmonary-function testing reveals a restrictive pattern and a disproportionate reduction in diffusing capacity. Patients often have hypoxemia, and the . . .
Notification of drug addicts.
Authors: D Acheson
Journal: BMJ (1990)

None the less, the paper does give some cause for optimism.Its authorship, from both medicine and personnel management, may reflect a new recognition that local solutions are more likely to come from cooperation than confrontation.It provides rare data to add to the continuing debate on what doctors actually do, and it notes (although, revealingly, no comment is made) that the ad- mitting house physician does not go to bed for 34 hours.Let us hope it is read by Mrs Bottomley and her working party.
Involvement of neurotrophins and their receptors in spondyloarthritis synovitis: relation to inflammation and response to treatment
Authors: M Rihl
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To investigate whether expression of the four members of the neurotrophin (NT) family and their four corresponding receptors is related to synovial inflammation in patients with spondyloarthritis (SpA). <b>Material and Methods:</b> Synovial fluid (SF) and serum NTs and their receptors were measured by ELISA. Immunohistochemistry was used for synovial tissue biopsy specimens from patients with SpA, rheumatoid arthritis, and osteoarthritis (OA). In SpA synovium, immunoreactivity of the receptors trkA and NGFRp75 was also assessed before and after 12 weeks of treatment with the monoclonal anti-tumour necrosis factor α antibody, infliximab. <b>Results:</b> mRNA transcripts of all NTs and receptors were expressed in the inflamed synovium. At the protein level, brain derived neurotrophic factor and NT-3 were significantly higher in the SF of patients with SpA than in those with OA. In contrast, ELISA of serum samples showed that the highest member in SpA was NT-4. Immunohistochemistry demonstrated that the NT receptors trkA and NGFRp75 were highly expressed in the inflamed synovium of patients with SpA, correlating with vascularity and lymphoid aggregates, respectively. Additionally, immunoreactivity of both receptors was significantly decreased after infliximab treatment. <b>Conclusions:</b> NTs and their receptors are expressed in inflamed peripheral joints of patients with SpA. Their expression is not constitutive but related to inflammation and they may be involved in the local disease processes.
Iron Chelation Improves Endothelial Function in Patients With Coronary Artery Disease
Authors: Stephen J. Duffy, Elizabeth S. Biegelsen, Monika Holbrook, Judson D. Russell, Noyan Gokce, John F. Keaney, Joseph A. Vita
Journal: Circulation (2001)

Some epidemiological studies have shown that increased iron stores are associated with increased cardiovascular events. Redox-active iron may contribute to lipid peroxidation, endothelial cell activation, and generation of reactive oxygen species (especially hydroxyl radical, via Fenton chemistry). Increased oxidative stress is associated with impaired action of endothelium-derived nitric oxide in patients with atherosclerosis.To test the hypothesis that reducing vascular iron stores would reverse endothelial dysfunction, we examined the effects of the iron chelator deferoxamine (500 mg intra-arterially over 1 hour) on vasomotor function in forearm resistance vessels of patients with coronary artery disease by venous occlusion plethysmography. Patients with coronary artery disease had impaired endothelium-dependent vasodilation in response to methacholine compared with healthy control subjects (P<0.001). Deferoxamine infusion decreased serum iron levels (P<0.001). Deferoxamine improved the blood flow response to methacholine in patients with coronary artery disease (P<0.01 by 2-way repeated-measures ANOVA) but had no effect on the response to sodium nitroprusside. In normal volunteers, deferoxamine had no effect on the response to methacholine. The nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine abolished augmentation of the methacholine response associated with deferoxamine. The hydroxyl radical scavenger mannitol had no effect on the methacholine response.Deferoxamine improved nitric oxide-mediated, endothelium-dependent vasodilation in patients with coronary artery disease. These results suggest that iron availability contributes to impaired nitric oxide action in atherosclerosis.
Treatment options in patients with decompensated cirrhosis, pre- and post-transplantation
Authors: Martina Gambato, Sabela Lens, Miquel Navasa, Xavier Forns
Journal: Journal of Hepatology (2014)

Interferon-based treatments have a poor safety profile and limited efficacy in patients with advanced liver disease and in patients with hepatitis C (HCV) recurrence after liver transplantation (LT). Despite the recent approval of the first interferon-free regimen, which will be followed by several other interferon-free combinations in 2014 and 2015, data in patients with advanced cirrhosis and hepatitis C after LT are still limited. One study has already proven the concept that graft HCV infection can be prevented in a significant proportion of patients by treating them with sofosbuvir and ribavirin while awaiting LT. Two interferon-free regimens have also demonstrated a high efficacy in patients with hepatitis C recurrence after transplantation. Before these treatment strategies can be implemented in clinical practice, a few issues need to be addressed: (1) safety and efficacy of new antivirals in patients with decompensated cirrhosis, (2) the impact of viral clearance on liver function, (3) the potential consequences of virological failure (and the selection of multi-drug resistant HCV strains) in patients with decompensated cirrhosis or with severe hepatitis C recurrence after LT, and (4) drug-drug interactions (DDI) profiles. Finally, in the transplant setting it is also relevant to learn which strategy is most cost-effective in minimizing the negative impact of hepatitis C: preventing graft infection by treating patients before transplantation or treating hepatitis C recurrence after LT.
Glucagon-Like Peptide-1 (7-37) Augments Insulin Release in Elderly Patients With Diabetes
Authors: Graydon S. Meneilly, Christopher H.S. McIntosh, Raymond A. Pederson, Joel F. Habener, Ronald Gingerich, Josephine M. Egan, Dariush Elahi
Journal: Diabetes Care (2001)

Glucagon-like peptide-1 (GLP-1) is a potent stimulator of glucose-induced insulin release (1). Unlike glucose-dependent insulinotropic polypeptide (GIP), GLP-1 augments insulin release in middle-aged patients with type 2 diabetes (1) and is therefore a potentially promising agent for the treatment of type 2 diabetes. We undertook the following experiments to determine whether the effects of GLP-1 on glucose-induced insulin release are preserved in elderly patients with diabetes.

These studies were conducted on 8 elderly patients with diabetes (age 77 ± 1 years, BMI 28 ± 1 kg/m2). The mean duration of diabetes was 8 ± 1 years and mean HbA1c was 7.1 ± 0.2%. All subjects were free of clinically apparent microvascular, macrovascular, or neuropathic complications. Patients with hypertension were not excluded. Three of the subjects were treated with sulfonylurea drugs, and four were being treated with angiotensin-converting enzyme inhibitors for hypertension. All medications were stopped at least 2 weeks before the test. This study was approved by the Committee on Human Investigation at the University of British Columbia. All subjects gave written informed consent before participation.

Each subject underwent two hyperglycemic clamp studies in random order, separated by at least 4 weeks (2 …
EFFECTS OF K201 ON REPOLARIZATION AND ARRHYTHMOGENESIS IN DOGS WITH CHRONIC COMPLETE ATRIOVENTRICULAR BLOCK
Authors: Thom R. Stams, Avram Oros, Roel van der Nagel, Jet D. Beekman, Paul Chamberlin, Howard C. Dittrich, Marc A. Vos
Journal: Journal of the American College of Cardiology (2011)
Acetazolamide Treatment of Hypokalemic Periodic Paralysis
Authors: ROBERT C. GRIGGS
Journal: Annals of Internal Medicine (1970)

Although individual attacks of hypokalemic periodic paralysis are lessened by potassium treatment, recurrence is frequently not prevented by prophylactic potassium administration. Twelve patients with hypokalemic periodic paralysis were treated with acetazolamide in a placebo-controlled trial. Whereas the majority had failed to improve with previous therapy, 10 of the 12 patients were dramatically improved by acetazolamide. This response has been maintained for periods of 16 to 43 months with minimal or no side effects. Several patients previously disabled are now asymptomatic. In addition to eliminating attacks of weakness, acetazolamide also improved interattack weakness in 8 of 10 affected patients. The mechanism of effect of acetazolamide was not discovered. Acetazolamide produced a mild metabolic acidosis but did not have a demonstrable effect on total body sodium, total body potassium, or thyroid function. Acetazolamide is the most effective treatment available for hypokalemic periodic paralysis.
100 000 excess civilian deaths in Iraq since March 2003
Authors: Owen Dyer
Journal: BMJ (2004)

The first scientific study of civilian casualties in Iraq has found that the rise in mortality from pre-invasion levels equates to 100 000 extra civilian deaths since March 2003. The research, published early online in the Lancet , concluded that violence has overtaken chronic disease as the leading cause of mortality since last year's invasion, and the leading cause of violent death has been airstrikes by coalition forces (www.thelancet.com/journal).

The findings are based on a survey funded by the Johns Hopkins Bloomberg School of Public Health, and by Iraqi doctors, who questioned 30 households in each of 33 randomly selected population clusters. Assuming an average seven residents in each household, the authors estimated their …
Lung sounds in asbestos induced pulmonary disorders
Authors: P. Piirilä, H. Lehtola, A. Zitting, L. Kivisaari, H. Koskinen, R. Luukkonen, S.P. Salo, T. Vehmas, H. Nordman, A.R.A. Sovijärvi
Journal: European Respiratory Journal (2000)

The aim of the study was to compare the lung sounds in patients with asbestos related pulmonary disorders with findings in high-resolution computed tomography (HRCT), and with lung function variables, in order to find out associations of acoustic changes with radiological fibrosis, emphysema or with pulmonary gas transfer functions. Sixty-four patients with asbestos-related pleural disease, with or without pulmonary disease, were studied. Lung sound recording and analysis was carried out with a computerized lung sound analyser, and HRCT of the chest, as well as forced spirometry and diffusing capacity measurement were performed. The fibrosis score correlated positively with the quartile frequencies of the power spectrum of lung sounds in inspiration (f50) and expiration (f50) and crackle count in inspiration, as well as negatively with diffusing capacity. When the patients with crackling sounds and significant fibrosis were excluded (n=18), emphysema correlated negatively with expiratory quartile frequencies of the power spectrum, with f25 and f50. Furthermore, diffusing capacity correlated with inspiratory f25 and forced expiratory volume in one second with inspiratory f50 when crackles and fibrosis were excluded. Changes in lung sounds were significantly associated with radiologically verified abnormalities and gas transfer of pulmonary tissue. High sound frequencies were associated with fibrotic changes of the lung while low sound frequencies with pulmonary emphysema. Acoustic analysis gives complementary clinical information for evaluation of asbestos-related pulmonary disorders.
Routine Sigmoidoscopy Costs and Usefulness
Authors: William Weiss
Journal: JAMA (1971)

<h3>To the Editor.—</h3> MEDICAL NEWS (<b>215</b>: 867-868, 1971) described a report by Bolt on the risk and expected gain of routine sigmoidoscopy. He estimated that 10,000 procedures produce a gain of six five-year survivors among 23 people with cancer of the colorectum, and one iatrogenic death. A common charge for sigmoidoscopy is $10. Therefore, the cost for 10,000 examinations is $100,000. Since the net gain is five "cures" (six "cures" minus one iatrogenic death), the cost per "cure" is $20,000 for the screening procedure alone. There is a fundamental assumption that routine sigmoidoscopy of asymptomatic people produces five-year survivals that would otherwise not occur. This assumption is based on the observation that retrospective studies of cancer cases show a five-year survival rate for asymptomatic people with colorectal cancer as high as 88%, compared to 50% in symptomatic patients (figures quoted in the news report). The assumption, however, may not be
Sponsorship of patients' groups by drug companies should be made transparent
Authors: Annette Tuffs
Journal: BMJ (2006)

Drug companies are sponsoring more and more groups for patients in Germany to increase demand for their products, but many members remain unaware of their involvement, a study has found. 

The firms are also advertising their products on what seem to be independent websites, despite laws that ban advertising prescription medicines to the public. 

The study, by the Zentrum fur Sozialpolitik of Bremen University, was commissioned by Germany's state health insurance companies and focused on the funding of groups for patients with chronic diseases, such as Alzheimer's disease and eczema. 

At present, health insurance companies are the main sponsor of patients' groups, spending a total €28m (£19m; $37m) in 2005, but drug companies are increasingly moving into the area. 

A quarter of patients' …
Local and systemic expression of basic fibroblast growth factor in a patient with familial glomangioma
Authors: N. Kapur, P. Lambiase, R.D. Rakhit, J. Pearce, G. Orchard, E. Calonje, P.M. Dowd
Journal: British Journal of Dermatology (2002)

Glomangiomas are rare cutaneous tumours composed of glomus cells, which are modified smooth muscle cells. The aetiology of this condition is thought to involve a mutation in a novel gene acting to regulate angiogenesis. We report a patient from a large family with three generations affected by familial multiple glomangiomas. We hypothesized that the growth factors basic fibroblast growth factor and vascular endothelial growth factor, which stimulate/regulate angiogenesis could be involved in the pathogenesis of these lesions. Therefore, using enzyme-linked immunosorbent assays and immunohistochemistry, respectively, we measured systemic and tissue levels of these growth factors in a patient with familial glomangiomas. In addition, we investigated endothelial mitogenicity of the patient's serum as a functional assay of systemic growth factor activity.
The Effects of Vasectomy on the Testis
Authors: Charles J. Flickinger
Journal: New England Journal of Medicine (1985)

The increased use of vasectomy for population control has led to a large number of animal studies on the morphologic, physiologic, and immunologic responses to this procedure. The extent, nature, and timing of morphologic alterations in the testis showed marked species variations and ranged from autoimmune orchitis to an absence of detectable changes. Physiologic studies indicated, contrary to expectation, that the hydrostatic pressure was elevated only in the distal part of the epididymis and not in the seminiferous tubules of several species. Immunologic studies have shown an increase in serum levels of antisperm antibody after vasectomy in a large number of species, but marked differences have been noted even between strains of a given species. In most cases, sperm appear to escape the duct system at some point, causing the formation of a spermatic granuloma. The location and time of development of granulomas after vasectomy may be related to regional differences in the distensibility of the duct system. Difficulties in obtaining tissue specimens have limited information about potential morphologic alterations in human testes after vasectomy, but spermatic granulomas have been reported. In addition, 50-70% of men are reported to have elevated serum levels of antisperm antibody after vasectomy. The relatively small proportion of men who become fertile after vasectomy reversal by vasovaostomy (40-70%) may involve antisperm antibodies in the serum or reproductive tract fluids. An immunologic response to extravasated spermatozoa may be involved in testicular alterations after vasectomy. The mechanism of the pathogenesis of testicular changes after vasectomy remains an important focus for research as the demand for vasectomy reversal continues to grow.
HOMOLOGOUS DISEASE IN THE ADULT RAT, A MODEL FOR AUTOIMMUNE DISEASE
Authors: Peter Stastny, Vernie A. Stembridge, Morris Ziff
Journal: The Journal of Experimental Medicine (1963)

The cutaneous lesions of adult rats with homologous disease are described, and evidence is presented to indicate that they have an immunologic basis. The skin changes included erythema, purpura, edema, and a variety of inflammatory lesions. In the more active lesions, dermal infiltration, hydropic degeneration, acanthosis, and atrophy of the epidermis with hyperkeratosis and follicular plugging were present. In some cases, ulceration and sloughing were also observed. More chronic lesions were characterized by atrophy of the epidermis and collagenization of the dermis with disappearance of the skin appendages. Rejection of autografts was observed simultaneously with acceptance of homografts. The histologic appearance of autografts undergoing rejection was similar to that of the spontaneous skin lesions, suggesting that the latter, too, had an immunologic basis. In favor of this, also, was the specificity of the dermatitis for the skin of the host, with sparing of neighboring homograft tissue. There was a histologic similarity between the spontaneous skin lesions of homologous disease and those of lupus erythematosus on the one hand, and scleroderma on the other, thus supporting the possibility that the cutaneous lesions of these connective tissue diseases of man may also have an immunologic basis. It was concluded that the adult rat with homologous disease may furnish a model for human autoimmune disease.
Classical and non-classical MHC I molecule manipulation by human cytomegalovirus: so many targets—but how many arrows in the quiver?
Authors: Anne Halenius, Carolin Gerke, Hartmut Hengel
Journal: Cellular and Molecular Immunology (2014)

Major mechanisms for the recognition of pathogens by immune cells have evolved to employ classical and non-classical major histocompatibility complex class I (MHC I) molecules. Classical MHC I molecules present antigenic peptide ligands on infected cells to CD8+ T cells, whereas a key function for non-classical MHC I molecules is to mediate inhibitory or activating stimuli in natural killer (NK) cells. The structural diversity of MHC I puts immense pressure on persisting viruses, including cytomegaloviruses. The very large coding capacity of the human cytomegalovirus allows it to express a whole arsenal of immunoevasive factors assigned to individual MHC class I targets. This review summarizes achievements from more than two decades of intense research on how human cytomegalovirus manipulates MHC I molecules and escapes elimination by the immune system.