tbuckley/cabot-search huggingface dataset:
THU0447 Insufficient Efficacy of Tocilizumab Therapy in Children with Castleman’s Disease
Authors: A. Kozlova, D. Konovalov, D. Abramov, A. Mitrofanova, A. Kislyakov, V. Roshchin, N. Miakova, I. Smirnova, E. Viktorova, A. Maschan, A. Shcherbina
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Castleman's disease (CD) or angiolymphoid vascular hyperplasia is a rare and not well recognized disease of unknown etiology characterized by a massive growth of lymphoid tissue that was first described in 1954, and subsequently better defined by Castleman in 1956. It usually appears in young adults whilst it rarely occurs in childhood. There are only about 100 pediatric cases published. CD is believed to be autoinflammatory in pathology and result in increased interleukin-6 secretion. Previous studies in adult patients suggested beneficial role of the anti-interleukin-6 receptor antibody tocilizumab in treatment of CD. We report 3 cases of multicentric Castleman's disease in children, treated in our Center in recent years <h3>Objectives</h3> To assess efficacy of tocilizumab therapy in children with Castleman's disease <h3>Methods</h3> 3 patients ages 4, 14 and 16 were diagnosed with multicentric Castleman's disease on the basis of clinical and histologic findings. 2 children (theboy of 4 years and the girl of 14 years) had hyaline-vascular type of CD, theboy of 16 years had plasma cell type of CD. The duration of illness before the correct diagnosis and beginning of treatment in the younger boy was 6 months, in the girl and the older boy - 6 years. All patients had enlarged lymph nodes of several groups and systemic involvement with fevers, weight loss, ascites, and progressive hematological changes (thrombocytopenia, anemia, high CRP). HHV-7 and 8 staining of the tissues were negative. In all cases treatment with tocilizumab as monotherapy was started at a dose of 8 mg/kg every 2 weeks <h3>Results</h3> 2 infusions in 2 children and 1 in one was performed. During the treatment period lymph nodes' sizes slightly decreased two patients and no lymph nodes size change was noted in the third patient. All patients continued to have progression of systemic symptoms. Therefore, Tocilizumab treatment was discontinued and substituted with more aggressive protocols consisting of cyclophosphamide, vincristine, prednisone and rituximab with fast effect: two children now are disease-free, the third one has marked improvement <h3>Conclusions</h3> Tocilizumabhas been reported to be effective for treatment of adults with CD, yet it proved insufficient activity in our three pediatric cases. In our experience CD in children has more aggressive course, therefore requiring chemotherapy aimed at lymphocytes' reduction <h3>Disclosure of Interest</h3> None Declared
Revisiting the Concept of Phenotypically Distinct Malignant Pancreatic Stem-Cell Subsets Based on Limiting Dilution Transplantation Assays
Authors: Thierry Bonnefoix, Mary Callanan
Journal: Journal of Clinical Oncology (2009)

In their review article, Lee et al 1 reported that phenotypic surface markers CD44, CD24, and ESA are putative cancer stem cell markers in pancreatic cancer.Based on these cell surface phenotypes, the authors claimed that distinct subpopulations were responsible for tumor initiation in pancreatic cancer.In their report, malignant pancreatic cells were sorted for the markers CD44, CD24, and ESA in combination.These sorted cells were reinjected into mice and their tumorigenic potential assessed by in vivo dilutional tumor propagation assays.The authors presented five limiting dilution transplantation assays (LDTAs) performed with varying number of input malignant pancreatic cell subsets.Based on the data presenting the number of transplanted mice with tumor outgrowth out of the total number of transplanted mice and reported in Table 1. 1 Lee et al 1 concluded that CD44ϩCD24ϩESAϩ malignant pancreatic cells are highly enriched for cancer stem cell function in comparison to unsorted cells, CD24ϩESAϩ, CD24ϪESAϪ, and CD44ϪCD24ϪESAϪ cells.However, no statistical analysis was reported that may validate these findings, and we are capable to demonstrate that appropriate statistical modeling of these LDTAs does not support the conclusion made by the authors. 1 Mathematical modeling of limiting dilution experiments of cells injected into recipient animals traditionally refers to a report published more than 45 years ago. 2 In this landmark study, clonogenic cell frequency estimates are based on the first term in the Poisson series, defining the well-known single-hit Poisson model (SHPM).The SHPM is unanimously used in limiting dilution experiments because the Poisson law adequately models the distribution of cells in a unit volume.
At the Bald Men's Convention
Authors: Walt McDonald
Journal: JAMA (2003)

Health Effects of OzoneO zone is a colorless gas that can be found in the upper atmosphere about 20 to 30 miles above the earth where it acts as a protective shield.Ozone prevents some of the sun' s cancer-causing ultraviolet rays (rays with a wavelength between that of visible light and x-rays) from reaching the earth' s surface.But when ozone forms near the surface of the earth, it can be harmful.If ozone is breathed in, it reacts with the tissues of the lung and can cause symptoms.When ozone levels are high, individuals with asthma often experience a harder time breathing, may have more asthma attacks, and need to use more medications.The October 8, 2003, issue of JAMA includes an article on the health effects of ozone among children with asthma.Ozone is formed through chemical reactions involving hydrocarbons and nitrogen oxide (types of pollution) and sunlight on calm summer days.Ozone peaks in the middle of the day throughout the summer months and is worse in cities with high levels of pollution or smog.Children who spend lots of time playing outside, persons with asthma, and elderly individuals are most at risk of the effects of ozone.
Case 18-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, William S. Beck, Thomas McC. Chesney
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 66-year-old woman was admitted to the hospital because of fever.She was well until 21 months previously, when there was the onset of progressive fatigue. Seventeen months before admission she entered the hospital because of increasing fatigue, with dyspnea, anorexia and weight loss. There was a history of excessive use of alcohol in the past. Physical examination revealed no lymphadenopathy. A Grade 3 precordial systolic ejection murmur was heard. The liver span was normal; the spleen extended nearly to the level of the umbilicus and was firm and nodular. There was + + + + asterixis. . . .
Case of Pernicious Anaemia Successfully Treated with Arsenic
Authors: J. Strachan
Journal: BMJ (1888)

that antipyrin would produce rise in temperature as well as fall.Antipyrin had very little action on the heart's muscle itself, andl probably the action of this drug as well as antifebrin influenced the circulation rather through the nervous system than through a direct action on the heart-walls or vessel-walls.-Dr.ILLING- WORTH (Accrington) thought that antipyretics such as antipyrin acted by preveniting the formation of fibrin.This was proved by the eyanosis induced by the drugs and by the reduction of oxybhmoglobin.These drugs ought, therefore, never to be used in diseases associated with diminution of fibrin; for example, typhoid and all germ dliseases.It was only safe to give them in cases of pyrexia due to catarrhal causes.Dr. MacAlister, one of the chief authorities on pyrexia, thought that ", the muscles were the chief furnaces of fever in health aiid disease."Dr. lllingworth thouglht lie was not warranted in cominig to such a conclusion, because there were not control experiments of such a nature as to indicate the effects of capillary circulation on rise of temperature.Cor- puscular friction in health and blood-stasis in disease were, how- ever, reasonable causes of thermogenesis.Again, Dr. MacAlister's experiments were p rrely physiological.Blood-stasis took no part in the conclusion, whilst all inflammatory processes were essen- tially associate(l with that process.Stasis caLused tension (and in maniy cases pain): tension excited the vasomotor nerves both peripherally and centrally, and the resuilt of both combined was inereasetl resistance and imcreased zvis et tergo.On the principle o)f " conservation of energy," increase(d friction in the circulatory
Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort
Authors: L. Byberg, H. Melhus, R. Gedeborg, J. Sundstrom, A. Ahlbom, B. Zethelius, L. G Berglund, A. Wolk, K. Michaelsson
Journal: BMJ (2009)

<b>Objective</b> To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation. <b>Design</b> Population based cohort study with follow-up over 35 years. <b>Setting</b> Municipality of Uppsala, Sweden. <b>Participants</b> 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years. <b>Main outcome measure</b> Total (all cause) mortality. <b>Results</b> The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking). <b>Conclusions</b> Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.
A Novel, Highly Sensitive ALK Antibody 1A4 Facilitates Effective Screening for ALK Rearrangements in Lung Adenocarcinomas by Standard Immunohistochemistry
Authors: Kim Gruber, Martin Kohlhäufl, Godehard Friedel, German Ott, Claudia Kalla
Journal: Journal of Thoracic Oncology (2015)
A CLINICAL LECTURE on a CASE of PNEUMONIA, with ABORTIVE CRISIS and PREMATURE RESOLUTION, FOLLOWED by SUPPURATION of BRONCHIAL GLANDS: Delivered at St. Mary's Hospital
Authors: W. Broadbent
Journal: BMJ (1898)

By the kind indulgence of my colleagues I have once more the privilege of giving a clinical lecture to the students of St. Mary's Hospital.I call it a clinical lecture, although you did not watch the course of the illness and follow the de- velopment of the symptoms with me at the bedside, inas- much as I take a case as a text and comment upon It as I go along.The physical signs are such as you will easily under- stand from description, and I hope to make clear the inferences and conclusions based upon them.The patient, a strong, healthy looking boy of 12, was taken ill on the evening of Thursday, December 2nd, 1897, when he was sick, and felt chilly.There was no distinct rigor.On the previous Saturday (five days before) he had played in a foot- ball match, and on the Monday had been out in the storm to watch the wrecking of the Broadstairs Pier.He had a slight cold and cough, as also had other boys in the school, butthere was nothing suggestive of influenza in the symptoms.The attack speedily assamed the characteristic features of pneu- monia, and when I saw him on the 5th, the temperature was 1050, the pulse 120, the respirations 48.There was a harsh cough, without expectoration, and pain in the right side, but in the abdomen rather than in the chest.The physical signs developed slowly, and it was only on the morning of this day that Dr. Raven had recognised indications of commencing consolidation at the right base.These were more distinct at the time of my visit, and distant tubular breathing was also to be heard above the spine of the scapula.We were agreed that the case was one of pneumonia, that the attack was severe, but that there were no special grounds for anxiety.A high temperature in pneumonia is not necessarily a very
Disturbance in respiratory mechanics in infants with bronchiolitis.
Authors: J Seidenberg, I B Masters, I Hudson, A Olinsky, P D Phelan
Journal: Thorax (1989)

The passive flow-volume and partial forced expiratory flow-volume techniques were used to assess pulmonary function in 14 spontaneously breathing infants with acute respiratory syncytial virus bronchiolitis. Two additional infants were studied while paralysed and ventilated. During the acute stage of the illness there was a significant reduction in forced expiratory flow rates and an increase in respiratory resistance. Although the mean thoracic gas volume for the group was increased, five infants did not compensate for their airways obstruction by hyperinflation. Curvilinear passive flow-volume curves were seen in three of the 14 non-ventilated infants and in both ventilated infants. At follow up three to four months later all passive flow-volume curves were linear. There was a significant reduction in hyperinflation and an increase in forced expiratory flow rates, but values still differed significantly from those in normal infants.
STUDIES ON ANTIBLASTIC IMMUNITY
Authors: Francis G. Blake
Journal: The Journal of Experimental Medicine (1917)

Antipneumococcus serum under certain conditions apparently inhibits or retards the metabolic activities of the homologous pneumococcus. Antipneumococcus serum exhausted of its agglutinin content possesses no inhibitory properties. The degree of inhibitory action of antipneumococcus serum parallels its agglutinating power. No evidence has been found to indicate that the inhibition of the metabolic activities of the pneumococcus by antipneumococcus serum is due to a specific antienzymotic property of the serum. The evidence which has been obtained indicates that the apparent inhibition of metabolic activity that occurs under certain conditions is due to agglutination of the pneumococci by the antipneumococcus serum and their consequent inability to grow in intimate contact with the whole medium. Antistaphylococcus serum inhibits the liquefaction of gelatin and the formation of pigment by Staphylococcus pyogenes aureus. Further experimentation is necessary to determine the mechanism of this inhibitory action. Antistaphylococcus serum does not inhibit those metabolic activities of Staphylococcus pyogenes aureus essential to the growth and multiplication of the organisms.
Bilateral anterior tibial claudication. Report of two cases in which the patients were cured by bilateral fasciotomy
Authors: B. M. Kennelly
Journal: JAMA (1968)

Fasciotomy relieved symptoms of claudication in both anterior tibial muscle compartments in two otherwise healthy adolescent patients. Effective blood flow in the muscles before surgery, measured with sodium chloride Na 22 clearance, was impaired after the patients had exercised, while intramuscular pressures in the anterior tibial compartments, measured by saline manometry, remained elevated for a longer than normal time following exercise. These results were compared with those found in two previously reported cases in which the patients were tested in this way.
Identification of genes involved in acute rejection following heart transplantation in a murine model: use of cDNA arrays
Authors: Ana L.S. Roussoulieres, Olivier Raisky, Lara Chalabreysse, George Dureau, Pascale Boissonnat, Jean-Francois Obadia, Francoise Thivolet-Bejui, John L. McGregor
Journal: Journal of the American College of Cardiology (2002)
Fallacy and controversy about base rates
Authors: Isaac Levi
Journal: Behavioral and Brain Sciences (1996)

Abstract Koehler's target article attempts a balanced view of the relevance of knowledge of base rates to judgments of subjective or credal probability, but he is not sensitive enough to the difference between requiring and permitting the equation of probability judgments with base rates, the interaction between precision of base rate and reference class information, and the possibility of indeterminate probability judgment.
The Brief Life of the National Center for Health Care Technology
Authors: Seymour Perry
Journal: New England Journal of Medicine (1982)

The National Center for Health Care Technology ceased to exist in December 1981. Established by Congress in 1978 and housed in the Department of Health and Human Services during its three-year life, the Center developed policies and procedures to assess medical technology from the standpoints of safety, efficacy, economics, ethics, and impact on society. It sponsored a sizable number of evaluations of technologies currently in use or beginning to come into use and established an extramural research program. Although the Center was reauthorized in the last session of Congress by the Budget Reconciliation Act of 1981, the Office of Management . . .
Health secretary publishes outcomes that will make NHS care "at least as good as any in world"
Authors: Z. Kmietowicz
Journal: BMJ (2010)

The government has published the health outcomes against which the NHS will be judged and which it says will refocus the NHS on patients’ health rather than centrally driven process targets. The Department of Health for England says that the NHS Outcomes Framework will provide a national overview of what the NHS will aim for when improving patients’ outcomes. It will also hold the NHS Commissioning Board to account when assessing how well the NHS is performing from 2012-13. Over the next two years the framework “will set the direction of travel” of the NHS. No “levels of ambition” will be set during this time, but the framework indicators will be refined, definitions formulated, and baselines set. The framework focuses on tackling inequalities in outcomes in five areas or “domains”:
Regulation of acylcoenzyme A. Cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity by lipoproteins in the intestine of parabiont rats.
Authors: B H Purdy, F J Field
Journal: Journal of Clinical Investigation (1984)

Parabiont rats were used to study the regulation of intestinal cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase activity) and esterification (acylcoenzyme A/cholesterol acyltransferase [ACAT] activity) by lipoproteins and micellar cholesterol. The parabiont rat model offers a unique way to observe changes in cholesterol metabolism in the intestine, independently of luminal factors. In one group of six surgically joined pairs, one animal was fed rat chow and 0.1% propylthiouracil (PTU). Its joined mate was fed rat chow, 0.1% PTU, 5% lard, and 0.3% taurocholic acid. In another group of five pairs, one rat was fed rat chow, 0.1% PTU, 5% lard, 0.3% taurocholic acid, plus 1% cholesterol. Its joined mate was fed the same diet except the cholesterol was deleted. Serum cholesterol changes were equal between members of a given pair, attesting to their common circulation. The administration of PTU itself caused a significant elevation of serum cholesterol. When one parabiont ingested cholesterol, serum cholesterol concentrations increased significantly for both pair members compared with control pairs not ingesting cholesterol. Hepatic and intestinal HMG-CoA reductase activities were significantly decreased in rats fed the diet containing cholesterol. ACAT activities in both organs were markedly increased. This supports previous data that suggest that dietary or luminal cholesterol affects both HMG-CoA reductase and ACAT activity in the small intestine. Moreover, in rats that were hypercholesterolemic but not ingesting dietary cholesterol, hepatic and intestinal reductase activities were decreased and ACAT activities were increased compared with the control animals. Intestinal microsomal cholesterol content was increased only in rats fed cholesterol. No changes in intestinal microsomal cholesterol were observed in the other animals. The data suggest that intestinal HMG-CoA reductase and ACAT activities are regulated by plasma lipoproteins independently of luminal factors. This nonluminal regulatory effect occurs without a measurable contribution to the intestinal microsomal cholesterol pool.
HLA haplotype sharing by siblings with rheumatoid arthritis: evidence for genetic heterogeneity.
Authors: D M Grennan, P A Sanders, P A Dyer, R Harris
Journal: Annals of the Rheumatic Diseases (1986)

HLA haplotype sharing was studied in 35 sibships in which there were two or more members with rheumatoid arthritis (RA). Haplotype sharing RA siblings was random in 15 sibships which included members with clinical or immunological features of autoimmune thyroid disease. In the remaining 20 'non-thyroid' sibships the frequencies of RA siblings sharing 0, 1, or 2 haplotypes were 0.04, 0.48, and 0.48 respectively (p = 0.006). 67% of RA probands in the 'thyroid' families and 90% in the other families were HLA-DR4 positive. It is suggested that there is genetic heterogeneity in the pathogenesis of RA with at least two independent genes within the major histocompatibility complex (MHC) predisposing to RA. One gene is in linkage disequilibrium with HLA-DR4, while results of comparison of DR antigen frequencies in DR4 negative RA and control groups suggest that the other is in linkage disequilibrium with HLA-DR1 and 3. In the thyroid disease families both genes are frequently present and as either may predispose to arthritis, HLA haplotype sharing is random. The frequencies of HLA haplotype sharing in the 'non-thyroid' families suggest that there is a dominant susceptibility gene in linkage disequilibrium with HLA-DR4, whose frequency is 5% and penetrance about 20%.
Leukemia-initiating cell activity requires calcineurin in T-cell acute lymphoblastic leukemia
Authors: S Gachet, E Genescà, D Passaro, M Irigoyen, H Alcalde, C Clémenson, S Poglio, F Pflumio, A Janin, C Lasgi, S Dodier, M Soyer, G Duménil, J Ghysdael
Journal: Leukemia (2013)