tbuckley/cabot-search huggingface dataset:
Immunological evaluation of cytokine and anticytokine immunotherapy in vivo: what have we learnt?
Authors: C. Jorgensen, F. Apparailly, J. Sany
Journal: Annals of the Rheumatic Diseases (1999)

Over the past five years, several immunotherapy trials have been performed in autoimmune diseases by targeting interleukin 1β (IL1β) (IL1 receptor antagonist (IL1-ra), IL-1 type I receptor), tumour necrosis factor (TNFα) (mAb anti-TNFα, soluble receptor RTNFp55 or p75 fusion protein, TNF binding protein), interleukin 6 (IL6) or Th2 cytokines like recombinant human interleukin 10 (rhuIL10) (table 1).1 One limitation of attempts to target a single cytokine is the overlap of the immune effects of IL1, TNFα, and IL6. However, the clinical trials indicate that inhibition of a single cytokine, despite the complexity of the network, is efficient. Moreover, the inhibition of major cytokines involved in host defence was found to be relatively well tolerated in the short-term, and few infections were reported. Paradoxically, very few data are available concerning effects of systemic delivery of rhuIL10 or cytokine antagonist on the immune system. This review analyses the available data on in vivo modification of the immune response after targeting a single cytokine (IL1β, TNFα, IL6 or IL10) in RA, and to extrapolate on combined biotherapeutic regimens.

View this table:

Table 1 
Cytokine and cytokine inhibitor approaches in RA



The immunopathology of RA synovitis is now better understood, and mediators of joint inflammation to be targeted have been identified. Whatever the initial antigenic stimulation, the proinflammatory cytokines IL1β, TNFα and IL6 play a pivotal part in all phases of rheumatoid arthritis (RA) disorder. The autoimmune process in RA may be arbitrarily subdivided into three chronological phases: the early inflammation phase, synovial proliferation and pannus formation in the chronic phase, cartilage degradation and repair in the last phase. At the early phase, memory CD45Ro T cells are attracted into the joint through a cascade of adhesion molecules induced by IL1β/TNFα and activated locally. IL6 and TNFα induce monocyte differentiation into dendritic cells CD14- CD83+ (DC). Macrophages …
Clonal T cell expansion induced by interleukin 2 therapy in blood and tumors.
Authors: A Kumar, F Farace, C Gaudin, F Triebel
Journal: Journal of Clinical Investigation (1996)

In a phase I clinical trial on the effects of preoperative adjuvant IL-2 therapy given to patients undergoing hepatic resection of colorectal adenocarcinoma metastases, we monitored the putative induction of T cell clonal expansion in both tissues and blood. The presence of T cell clonotypes was analyzed with a PCR-based method that determines V-D-J junction size patterns in T cell receptor (TCR) V beta subfamilies in samples before and after a 5-d IL-2 infusion. This high resolution method analyzing CDR3 sizes of TCR transcripts was used in conjunction with FACS analysis of the corresponding T cell subpopulations with TCR V beta-specific mAb. At time of surgery (day 8 after starting IL-2), we found in the three patients analyzed with V beta-C beta primers multiple dominant T cell clonotypes in the tumor and peritumoral tissues which had probably expanded as a result of therapy. In three control patients not treated with IL-2, multiple oligoclonal patterns were not observed with this set of primers. In the fourth control patient a unique V beta 21-C beta CDR3 pattern which corresponds to two dominant clonotypes was found in the tumor. The same dominant clonotypes identified in the tumor after IL-2 were also detectable in the blood and comparison of the profiles obtained before and after IL-2 therapy indicates that they were induced by IL-2. The relative expansion of the corresponding T cell subpopulations was maintained for varying periods of time after surgery (4-7 d and almost 2 yr in one case). Together, these results indicate that IL-2 induces marked expansion of several T cell clones. Systemic IL-2 administration may represent, either alone or as a vaccine adjuvant, an appropriate way of boosting antigen-specific immune responses.
Equestrian Injuries
Authors: John A. I. Grossman
Journal: JAMA (1978)

In a prospective study involving 110 injured equestrians, there were no noteworthy correlations between age, sex, or experience of the amateur riders and injury occurrence. Tack failure caused several injuries. Among fox hunters the incidence was related only to frequency of hunts. The most common severe injury was to the head, associated with lack of headgear. Fewer than 20% of the 110 riders used a protective helmet. There were four renal contusions and one bladder laceration. The most frequent injuries were fractures of the upper extremities. Wearing a good-quality protective helmet and checking tack are important for injury prevention.
Will Mountains Trekkers Have Heart Attacks?
Authors: Drummond Rennie
Journal: JAMA (1989)

A consequence of the fitness boom has been that it is now commonplace for symptomless people to go to their physicians to be checked out before they take up jogging, racquetball, or aerobic dancing. What most people are concerned about is the presence of coronary arterial disease and the possibility that the exercise will cause sudden death or myocardial infarction. The public, persuaded that such checkups are as crudely mechanistic as those for automobiles, is happy to pay physicians to carry them out, although there is little evidence that such routine checks effectively reduce morbidity or mortality from subsequent exercise. Increasing affluence and a greater interest in the outdoors have caused ever larger numbers of people to go to the mountains to exercise—either to climb, walk (trek), or ski cross-country. (Downhill skiing, where the work is done by the lift, is not an impressive aerobic challenge.) Many of these people
Points: Not an accident or emergency
Authors: P J M Davies
Journal: BMJ (1980)

<h3>BACKGROUND AND PURPOSE:</h3> Alleviation of aneurysm induced mass effect has been difficult with both conventional endovascular and surgical techniques. Our aim was to study the efficacy of endovascular flow modification on aneurysm-induced mass effect and compression syndrome, as demonstrated by cross-sectional imaging studies and clinical follow-up. <h3>MATERIALS AND METHODS:</h3> Thirty aneurysms larger than 10 mm were treated by flow diversion alone and previously had undergone pre- and posttreatment cross-sectional imaging. Pretreatment MR imaging or contrast CT, follow-up angiography at 6 months, and follow-up MR imaging studies between 6 and 18 months were retrospectively analyzed. The neurologic and neuro-ophthalmologic statuses of all patients were recorded before treatment and at the time of follow-up cross-sectional imaging. <h3>RESULTS:</h3> At 6 months, 28 aneurysms were completely occluded, 1 had a neck remnant, and 1 had residual filling on angiography. Between 6 and 18 months, 3 aneurysms decreased in size and 27 completely collapsed as demonstrated on MR imaging. Before treatment, 6 patients had vision loss, 10 had double vision due to a third or sixth nerve palsy or both, and 1 had hemiparesis due to brain stem compression. On MR imaging follow-up, vision loss had either improved or resolved in all except 1 patient, double vision had resolved completely (7/10) or partially (3/10), and the patient with brain stem compression became asymptomatic. There was no bleeding observed in this series. One parent artery thrombosis resulted in a major infarct. <h3>CONCLUSIONS:</h3> Endovascular flow diversion is a highly effective technique for resolving radiologic mass effect and clinical compression syndromes.
Sustained Normalization of Neurological Disease after Intracranial Gene Therapy in a Feline Model
Authors: Victoria J. McCurdy, Aime K. Johnson, Heather L. Gray-Edwards, Ashley N. Randle, Brandon L. Brunson, Nancy E. Morrison, Nouha Salibi, Jacob A. Johnson, Misako Hwang, Ronald J. Beyers, Stanley G. Leroy, Stacy Maitland, Thomas S. Denney, Nancy R. Cox, Henry J. Baker, Miguel Sena-Esteves, Douglas R. Martin
Journal: Science Translational Medicine (2014)

In a feline model of lysosomal storage disease, intracranial gene therapy achieved therapeutic efficacy in the CNS and increased long-term survival.
Medical Screening of Immigrants
Authors: G. L. Robinson
Journal: BMJ (1965)

repeatedly emphasized recently.2 3Supple- mentary potassium ion cannot be retained by the kidney unless chloride ion is also avail- able.Recent work has shown that patients in chronic heart failure may have a serious deficit of total body potassium which is in no way influenced by the administration of any amount of non-chloride-containing potassium salts, and it is high time that effervescent potassium be deleted from the British Pharmaceutical Codex.Preliminary estima- tions in this hospital of total body potassium in patients treated in this way have indicated a serious deficit even though serum levels were normal.
Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients.
Authors: T P Leist, K Frei, S Kam-Hansen, R M Zinkernagel, A Fontana
Journal: The Journal of Experimental Medicine (1988)

To evaluate the potential role of cachectin/TNF-alpha in the pathogenesis of bacterial and viral meningitis, concentrations and kinetics of TNF-alpha were determined in cerebrospinal fluid (CSF). After intracerebral, but not systemic, infection with Listeria monocytogenes in mice, TNF-alpha was detected as early as 3 h after infection reaching maximum titers after 24 h. However, TNF-alpha was not found in serum during the course of Listeria infection. In contrast to bacterial meningitis, no TNF-alpha was detected at any time in CSF of mice suffering from severe lymphocytic choriomeningitis induced by intracerebral infection with lymphocytic choriomeningitis virus. This difference is striking since both model infections led to a massive infiltration of polymorphonuclear and mononuclear leukocytes into the meninges and CSF. The results found for the two model infections were paralleled by findings in humans; CSF from three out of three patients with bacterial meningitis examined during the first day of hospitalization showed significant levels of TNF-alpha; none of the CSF obtained later than 3 d after hospitalization was positive. In addition, similarly to what was found in mice with viral meningitis, zero out of seven patients with viral meningitis had detectable TNF-alpha in CSF.
Rallying the Caucus — The Democrats' Struggle for Unity on Reform
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2009)

Fighting Republicans and a few wary Democrats as he races against the clock, Senate Majority Leader Harry Reid (D-NV) must muster 60 votes to defeat an anticipated series of GOP procedural measures, including a filibuster, and clear the way for enacting ambitious health care reform legislation. Underscoring the need for the vote of every senator in the Democratic caucus, Reid agreed, in exchange for the support of party moderates and independent Joseph Lieberman of Connecticut, to drop a plan to expand Medicare by enabling people 55 to 64 years of age to enroll in the program. Having thus revised their . . .
Hematologic Effects of Interleukin-1β, Granulocyte Colony-Stimulating Factor, and Granulocyte-Macrophage Colony-Stimulating Factor in Tumor-bearing Mice Treated With Fluorouracil
Authors: M. A. S. Moore, R. L. Stolfi, D. S. Martin
Journal: JNCI Journal of the National Cancer Institute (1990)

Myelosuppression following intensive chemotherapy in cancer patients is associated with increased morbidity and mortality. Hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), alone or in combination with interleukin-1 (IL-1), have been shown to counteract myelosuppression resulting from some, but not all, chemotherapeutic regimens. In an attempt to apply these findings to intensive therapy with proliferation-dependent chemotherapeutic drugs such as fluorouracil (5-FU), we investigated combination biochemotherapy in a murine model. Female CD8F 1 [(BALB/c × DBA/8)F 1 ] mice bearing first-passage transplants of spontaneous CD8F 1 breast tumors were treated intraperitoneally once a week for 3 successive weeks with a course of 5-FU alone or with a course of 5-FU in combination with recombinant human interleukin-1β (rHuIL-1β) alone or in combination with CSFs. rHuIL-1β alone or in combination with rHuG-CSF or recombinant murine GM-CSF significantly improved tumor growth inhibition (60% vs. 90%) and survival (20% vs. 90%–100%), increased the maximally tolerated dose of 5-FU, accelerated recovery of neutrophil counts in peripheral blood, and reduced duration of significant neutropenia and loss of body weight (29% vs. 10% loss). Clinical trials of IL-1 have been initiated in patients with advanced cancer receiving multiple courses of high-dose 5-FU.
A case-control study on a novel DNA virus (TT virus) infection and hepatocellular carcinoma
Authors: Alessandro Tagger, Francesco Donato, Maria Lisa Ribero, Giorgio Binelli, Umberto Gelatti, Giuseppe Portera, Alberto Albertini, Michele Fasola, Roberta Chiesa, Giuseppe Nardi
Journal: Hepatology (1999)

We performed a case-control study to evaluate the association of a new human DNA virus named TT virus (TTV) with hepatocellular carcinoma (HCC). We recruited 174 subjects hospitalized for HCC (84% males; mean age: 64 years) and 118 patients hospitalized for non-liver diseases in Brescia, northern Italy, as controls (94% males; mean age: 66 years). TTV DNA was found in serum by polymerase chain reaction (PCR) in 26 cases (15%) and 11 controls (9.3%) ( P &gt; .1). TTV group 2 infection was identified in 16 cases (61.5%) and 4 controls (36.4%) ( P &gt; .1) using a type-specific PCR method. Sequence analysis of 222 nt of TTV DNA demonstrated that the remaining 10 cases and 7 controls were all infected by group 1. The odds ratio (OR) for TTV-DNA positivity, adjusted for demographic variables, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, and heavy alcohol intake was 1.8 (95% CI: 0.7-4.8; P &gt; .1). The OR did not change when the analysis was restricted to 14 HCC cases and 56 controls who were negative for each known risk factor for HCC (OR = 1.7; 95% CI: 0.8-4.0). TTV-DNA positivity was not associated with transfusion history. The prevalence of TTV DNA was higher among HCC cases positive for HBsAg (10 of 38 [26.3%]) than among those positive for HCV RNA (8 of 62 [12.9%]) or negative for hepatitis B virus (HBV), HCV, and hepatitis G virus (HGV) infections (5 of 62 [8.1%]) ( P = .02). This study does not support the hypothesis of an association between TTV infection and HCC.
777 SUSTAINED VIROLOGICAL RESPONSE IS ASSOCIATED WITH A LOWER RISK OF COMPLICATIONS AND HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HCV RELATED CIRRHOSIS
Authors: A.C. Cardoso, R. Moucari, N. Giuily, C. Figueiredo-Mendes, N. Boyer, M.P. Ripault, C. Castelnau, T. Asselah, M. Martinot-Peignoux, S. Maylin, P. Bedossa, P. Marcellin
Journal: Journal of Hepatology (2008)
RELATIONSHIP OF BISPHOSPHONATE THERAPY AND ATRIAL FIBRILLATION/ATRIAL FLUTTER: THE OSTEOPOROTIC FRACTURES IN MEN (MROS) STUDY
Authors: Samir R. Thadani, Bryan Ristow, Richard E. Shaw, Terri Blackwell, Katie L. Stone, Reena Mehra, Steven R. Cummings, Peggy M. Cawthon
Journal: Journal of the American College of Cardiology (2011)
The Graham-Cole 'Test' Revisited
Authors: Harold G. Jacobson
Journal: JAMA (1983)

The pioneer efforts of Graham and Cole to produce a radiological examination of the gallbladder were prompted by a desire to enhance and refine the diagnosis of gallbladder disease beyond that achieved by history and physical examination. It is interesting to consider the background of the period in which the Graham-Cole test was designed. The specialty of radiology was not yet in formal existence (the American Board of Radiology was not organized until 1934). Drs Graham and Cole were not even radiologists. Both men, being members of the Department of Surgery at Washington University School of Medicine, undoubtedly felt ill at ease about exploring or removing a gallbladder without first ascertaining its pathological state. The hazards of surgery, particularly those of anesthesia, were, of course, much greater than they are today, so that proper indications for surgery were paramount. In addition to its relevance for surgeons, the article by Graham
Characterization of a Large Panel of Patient-Derived Tumor Xenografts Representing the Clinical Heterogeneity of Human Colorectal Cancer
Authors: Sylvia Julien, Ana Merino-Trigo, Ludovic Lacroix, Marc Pocard, Diane Goéré, Pascale Mariani, Sophie Landron, Ludovic Bigot, Fariba Nemati, Peggy Dartigues, Louis-Bastien Weiswald, Denis Lantuas, Loïc Morgand, Emmanuel Pham, Patrick Gonin, Virginie Dangles-Marie, Bastien Job, Philippe Dessen, Alain Bruno, Alain Pierré, Hugues De Thé, Hany Soliman, Manoel Nunes, Guillaume Lardier, Loreley Calvet, Brigitte Demers, Grégoire Prévost, Patricia Vrignaud, Sergio Roman-Roman, Olivier Duchamp, Cyril Berthet
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and advanced preclinical models. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer (CRC) models. Experimental Design: From the 85 unsupervised surgical colorectal samples collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinoses and 14 metastases. Histologic and molecular characterization of patient tumors, first and late passages on mice includes the sequence of key genes involved in CRC (i.e., APC, KRAS, TP53), aCGH, and transcriptomic analysis. Results: This comprehensive characterization shows that our collection recapitulates the clinical situation about the histopathology and molecular diversity of CRC. Moreover, patient tumors and corresponding models are clustering together allowing comparison studies between clinical and preclinical data. Hence, we conducted pharmacologic monotherapy studies with standard of care for CRC (5-fluorouracil, oxaliplatin, irinotecan, and cetuximab). Through this extensive in vivo analysis, we have shown the loss of human stroma cells after engraftment, observed a metastatic phenotype in some models, and finally compared the molecular profile with the drug sensitivity of each tumor model. Through an experimental cetuximab phase II trial, we confirmed the key role of KRAS mutation in cetuximab resistance. Conclusions: This new collection could bring benefit to evaluate novel targeted therapeutic strategies and to better understand the basis for sensitivity or resistance of tumors from individual patients. Clin Cancer Res; 18(19); 5314–28. ©2012 AACR.
Harm minimisation for drug misusers.
Authors: I. McKee
Journal: BMJ (1992)

metal's angina are both given as contraindications in the datasheet for sumatriptan; the datasheet also includes advice against the concomitant use of ergotamine.Willett and colleagues' report there- fore clearly highlights the need for these warnings and emphasises that sumatriptan should be avoided if there is a history of ischaemic heart disease or undiagnosed chest pain.
Reproducibility of skin prick test results in epidemiologic studies: a comparison of two devices
Authors: S. Illi, L. Garcia‐Marcos, V. Hernando, J. J. Guillen, A. Liese, E. von Mutius
Journal: Allergy (1998)

The reproducibility of skin prick tests under field conditions is essential for comparing prevalences between centers in epidemiologic multicenter studies. This study aimed to evaluate and compare the reproducibility of two widely used skin prick test devices: the Multi‐Test and the ALK lancet. The subjects were 28 children, aged 6–14 years, with known sensitivities Dermatophagoides pteronyssinus (D. pter). Both devices were applied to each subject on two occasions, 1 week apart, by different, randomly assigned fieldworkers, using histamine, negative control, and the D. pter. allergen extract. For all three tested solutions, mean wheal sizes were larger for the Multi‐Test than for the ALK lancet. The coefficient of variation for histamine was 21.8% for the Multi‐Test and 17.3% for the ALK lancet. The coefficients of variation for the allergen D. pter. amounted to 47.4% for the Multi‐Test and to 24.6% for the ALK lancet. The percentage of concordant test results was 92.6% for the Multi‐Test and 100.0% for the ALK lancet for a cutoff point of wheal size equal to or greater than 1 mm. The results of this study suggest that the single ALK lancet performs slightly better than the Multi‐Test device with respect to reproducibility under conditions of epidemiologic field studies.
Is it worth a dam?
Authors: S Joyce
Journal: Environmental Health Perspectives (1997)

Once a sign of modernization and growth, dams are often seen today as symbols of environmental and social devastation. Over 800,000 dams have been built worldwide to provide drinking water, flood control, hydropower, irrigation, navigation, and water storage. Dams do indeed provide these things,but at the cost of several adverse, unexpected effects: disruption of ecosystems, decline of fish stocks, forced human and animal resettlements, and diseases such as malaria, which are borne by vectors that thrive in quiet waters.
Social consequences of sleep disordered breathing on patients and their partners: a controlled national study
Authors: Poul Jennum, Rikke Ibsen, Jakob Kjellberg
Journal: European Respiratory Journal (2013)

We aimed to evaluate the total costs to patients and their partners of sleep apnoea and obesity hypoventilation syndrome (OHS) and their treatment, as this is poorly described in families. Using data from the Danish National Patient Registry and other public databases, all patients and their partners with a diagnosis of sleep apnoea (n=30,278) or OHS (n=1562) were included. They were compared with age-, sex- and community location-matched citizens at a ratio 1:4 (120,506 and 6241 control subjects, respectively). Direct and indirect costs were evaluated for patients and their partners. Sleep apnoea and OHS patients and their partners had higher rates of health-related contact, medication use and unemployment, and lower income levels. Excess yearly direct net health and foregone earnings (indirect costs) were €2174 and €7981 prior to diagnosis, and €3988 and €12,022 after diagnosis for sleep apnoea and OHS, respectively. The comparable annual mean excess health-related costs for spouses were €1965 and €2862 before diagnosis, and €2307 and €3079 after diagnosis, for sleep apnoea and OHS patients, respectively. These socioeconomic consequences were present up to 12 years before first diagnosis, and increased as the disease advanced. Sleep-disordered breathing has major socioeconomic consequences for patients and their spouses years before and after diagnosis.
Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma
Authors: Yang Yu, Zhao-Hui Wang, Liang Zhang, Hong-Juan Yao, Yan Zhang, Ruo-Jing Li, Rui-Jun Ju, Xiao-Xing Wang, Jia Zhou, Nan Li, Wan-Liang Lu
Journal: Biomaterials (2011)