tbuckley/cabot-search huggingface dataset:
Oesophageal stricture associated with Crohn's disease.
Authors: N H Dyer, P L Cook, R A Kemp Harper
Journal: Gut (1969)

Regional enteritis was originally described as a disease of the terminal ileum (Crohn, Ginzburg, and Oppenheimer, 1932).This concept of the condition has gradually been broadened and it is now realized that similar histopathological lesions may involve any part of the alimentary tract from stomach to anus (Crohn and Yunich, 1941; Lockhart-Mummery and Morson, 1960; Wolf and Marshak, 1962; Pryse-Davies, 1964).Many authors also mention that Crohn's disease may occasionally involve the oesophagus (Crohn and Yarnis, 1958), but there are very few case reports in the literature and other authorities doubt whether such lesions are really manifestations of Crohn's disease (Cooke, 1955).We report two patients with Crohn's disease in whom radiological and endoscopic abnormalities of the lower oesophagus were found.In one of these patients surgical resection was performed thus providing full-thickness sections of the wall for histological examination.CASE REPORTS CASE 1 (J.W.) In 1946, when aged 36, this man deve- loped recurrent ulceration of the mouth.Each attack commenced as crops of vesicles which developed into
IL-4R Drives Dedifferentiation, Mitogenesis, and Metastasis in Rhabdomyosarcoma
Authors: Tohru Hosoyama, Mohammed Imran Aslam, Jinu Abraham, Suresh I. Prajapati, Koichi Nishijo, Joel E. Michalek, Lee Ann Zarzabal, Laura D. Nelon, Denis C. Guttridge, Brian P. Rubin, Charles Keller
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. The alveolar subtype of rhabdomyosarcoma (ARMS) is a paradigm for refractory and incurable solid tumors because more than half of the children at diagnosis have either regional lymph node or distant metastases. These studies follow our previous observation that Interleukin-4 receptor α (IL-4Rα) is upregulated in both human and murine ARMS, and that the IL-4R signaling pathway may be a target for abrogating tumor progression. Experimental Design: By in vitro biochemical and cell biology studies as well as preclinical studies using a genetically engineered mouse model, we evaluated the role of IL-4 and IL-13 in IL-4R–mediated mitogenesis, myodifferentiation, and tumor progression. Results: IL-4 and IL-13 ligands accelerated tumor cell growth and activated STAT6, Akt, or MAPK signaling pathways in the human RMS cell lines, RD and Rh30, as well as in mouse primary ARMS cell cultures. IL-4 and IL-13 treatment also decreased protein expression of myogenic differentiation factors MyoD and Myogenin, indicating a loss of muscle differentiation. Using a genetically engineered mouse model of ARMS, we have shown that inhibition of IL-4R signaling pathway with a neutralizing antibody has a profound effect on the frequency of lymph node and pulmonary metastases, resulting in significant survival extension in vivo. Conclusions: Our results indicate that an IL-4R-dependent signaling pathway regulates tumor cell progression in RMS, and inhibition of this pathway could be a promising adjuvant therapeutic approach. Clin Cancer Res; 17(9); 2757–66. ©2011 AACR.
Reduced Interferon- γ Expression in Peripheral Blood Mononuclear Cells of Infants with Severe Respiratory Syncytial Virus Disease
Authors: JUDITH H. ABERLE, STEPHAN W. ABERLE, MICHAEL N. DWORZAK, CHRISTIAN W. MANDL, WINFRIED REBHANDL, GEORG VOLLNHOFER, MICHAEL KUNDI, THERESE POPOW-KRAUPP
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We examined the in vivo cell-mediated immune response in infants with respiratory syncytial virus (RSV) infection in order to gain information about the pathogenesis of severe RSV disease in infancy. Semiquantitative reverse transcription-polymerase chain reaction and three-color flow cytometry were used to determine the levels of messenger RNA (mRNA) for interferon (IFN)-gamma in peripheral blood mononuclear cells, and the distribution of lymphocyte subsets in infants with acute RSV infection. The findings were correlated with the severity of the patients' illness and the production of RSV-specific IgE antibodies (RSV-IgE). Significantly lower IFN-gamma levels and T-lymphocyte counts in the acute phase of illness were observed in infants with severe RSV disease than in those with a milder clinical course of illness. The induction of RSV-IgE was not related to IFN-gamma levels in the acute phase of illness, but rather correlated with IFN-gamma expression during convalescence. The data indicate that reduced IFN-gamma expression may be an important factor in the pathogenesis of severe RSV disease in infancy.
Viral induction of a chronic asthma phenotype and genetic segregation from the acute response
Authors: Michael J. Walter, Jeffrey D. Morton, Naohiro Kajiwara, Eugene Agapov, Michael J. Holtzman
Journal: Journal of Clinical Investigation (2002)

Paramyxoviral infections cause most of the acute lower respiratory tract illness in infants and young children and predispose to the development of chronic wheezing, but the relationship between these short- and long-term viral effects are uncertain. Here we show that a single paramyxoviral infection of mice (C57BL6/J strain) not only produces acute bronchiolitis, but also triggers a chronic response with airway hyperreactivity and goblet cell hyperplasia lasting at least a year after complete viral clearance. During the acute response to virus, same-strain ICAM-1-null mice are protected from airway inflammation and hyperreactivity despite similar viral infection rates, but the chronic response proceeds despite ICAM-1 deficiency. Neither response is influenced by IFN-gamma deficiency, but the chronic response is at least partially prevented by glucocorticoid treatment. In contrast to viral infection, allergen challenge caused only short-term expression of asthma phenotypes. Thus, paramyxoviruses cause both acute airway inflammation/hyperreactivity and chronic airway remodeling/hyperreactivity phenotypes (the latter by a hit-and-run strategy, since viral effects persist after clearance). These two phenotypes can be segregated by their dependence on the ICAM-1 gene and so depend on distinct controls that appear critical for the development of lifelong airway diseases such as asthma.
UTAH'S EXPERIENCE WITH THE NATIONAL DRAFT ACT FOR HOSPITALIZATION OF THE MENTALLY ILL
Authors: C. H. HARDIN BRANCH
Journal: American Journal of Psychiatry (1952)

1.The experience of a year with the Federal Security Agency Draft Act incorporated into the State Law of Utah in May, 1951, indicates that this "model law" has distinct advantages and, in general, has proved itself to be efficient and workable. 2. Two major and rather important revisions of the law are indicated: (a). Provision for some form of legally authorized medical personnel to handle the patient who is not dangerous, but is merely uncooperative, lacking in insight, stubborn, or recalcitrant. These persons would have authority to assist in the examination of such patients and to transport them to the hospital as directed by the appropriate commitment procedure. (b). A regularly constituted medical authority to review the admissions to the hospital and investigate complaints, thus protecting the superintendent and his staff from the often unjust criticism directed at them and protecting the patients from those rare situations in which there is grossly inadequate care and observation.
Multiple crashes on motor ways.
Authors: M S Christian
Journal: BMJ (1972)

suspected until a few months before death when increased pain necessitated surgery.All these patients had severe anaemia (Hb 55-60%) at diagnosis.All had a longstanding history of duodenal ulcer and were then found to have gastric cancer.It seems, therefore, that such cases need very careful examination if they come to operation for a duodenal ulcer.Tragically, all were late diagnoses chiefly because dyspeptic symp- toms were wrongly interpreted in the 16-12 months before laparotomy.It is said that duodenal ulcer and gastric cancer only rarely coexist,' and a report from the Birmingham Regional Cancer Registry and the United Birmingham Hos- pitals stated that no association was found between cancer and peptic ulcer.2-Iam, etc.,
Erosive osteoarthritis: a more severe form of radiographic hand osteoarthritis rather than a distinct entity?
Authors: Michelle Marshall, Elaine Nicholls, Wing-Yee Kwok, George Peat, Margreet Kloppenburg, Danielle van der Windt, Helen Myers, Krysia Dziedzic
Journal: Annals of the Rheumatic Diseases (2013)

Objectives To determine whether erosive osteoarthritis shares the same pattern of joint involvement and risk profile as increasing grades of non-erosive hand osteoarthritis. Methods Participants were from two population-based cohorts, aged ≥50 years, reporting hand symptoms in the previous month. Interphalangeal joints were assessed for erosive osteoarthritis (Verbruggen–Veys erosive or remodelled phase) and radiographic osteoarthritis (sliding cut-offs of K&amp;L≥2, K&amp;L≥3 and K&amp;L=4). At the joint level, similarities in the frequency and pattern of erosive and non-erosive osteoarthritis were assessed by Spearman's rank correlation coefficients and generalised estimating equations. At the person level, individuals with erosive osteoarthritis were compared to those with non-erosive osteoarthritis using logistic regression, adjusted for age and gender (aOR), for the following exposures: family history, previous injury, overuse and metabolic factors (BMI, dyslipidaemia, hypertension, diabetes). Results In 1076 symptomatic participants the ranked frequency of involvement for erosive joints was comparable to joints with K&amp;L≥3 and K&amp;L=4 (r&gt;0.95). Patterns of joint involvement in erosive osteoarthritis were strongest for symmetry (aOR=6.5; 95% CI 3.0 to 14.1), followed by row (2.0; 0.8 to 5.0) and ray (0.3; 0.0 to 2.5), which was similar to joints with K&amp;L≥3 and K&amp;L=4. Individuals with erosive osteoarthritis (n=80) had an increased risk of metabolic syndrome (2.7; 1.0 to 7.1), notably dyslipidaemia (4.7; 2.1 to 10.6) compared with non-erosive osteoarthritis classed K&amp;L≥3 (n=193). Conclusions The similar frequency of radiographic joint involvement and patterning in erosive osteoarthritis and more severe non-erosive osteoarthritis is consistent with prevalent erosive osteoarthritis being a severe form of hand osteoarthritis rather than a distinct entity. Metabolic exposures, dyslipidaemia in particular, may be implicated in erosive osteoarthritis.
Germinal center B cells govern their own fate via antibody feedback
Authors: Yang Zhang, Michael Meyer-Hermann, Laura A. George, Marc Thilo Figge, Mahmood Khan, Margaret Goodall, Stephen P. Young, Adam Reynolds, Francesco Falciani, Ari Waisman, Clare A. Notley, Michael R. Ehrenstein, Marie Kosco-Vilbois, Kai-Michael Toellner
Journal: The Journal of Experimental Medicine (2013)

Affinity maturation of B cells in germinal centers (GCs) is a process of evolution, involving random mutation of immunoglobulin genes followed by natural selection by T cells. Only B cells that have acquired antigen are able to interact with T cells. Antigen acquisition is dependent on the interaction of B cells with immune complexes inside GCs. It is not clear how efficient selection of B cells is maintained while their affinity matures. Here we show that the B cells’ own secreted products, antibodies, regulate GC selection by limiting antigen access. By manipulating the GC response with monoclonal antibodies of defined affinities, we show that antibodies in GCs are in affinity-dependent equilibrium with antibodies produced outside and that restriction of antigen access influences B cell selection, seen as variations in apoptosis, plasma cell output, T cell interaction, and antibody affinity. Feedback through antibodies produced by GC-derived plasma cells can explain how GCs maintain an adequate directional selection pressure over a large range of affinities throughout the course of an immune response, accelerating the emergence of B cells of highest affinities. Furthermore, this mechanism may explain how spatially separated GCs communicate and how the GC reaction terminates.
Comparison of Large Versus Smaller Randomized Trials for Mental Health-Related Interventions
Authors: Despina G. Contopoulos-Ioannidis, Simon M. Gilbody, Thomas A. Trikalinos, Rachel Churchill, Kristian Wahlbeck, John P.A. Ioannidis
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The extent of disagreement between large and smaller randomized, controlled trials on mental health issues is unknown. The authors aimed to compare the results of large versus smaller trials on mental health-related interventions. METHOD: The authors screened 161 Cochrane and 254 Database of Abstracts of Reviews of Effectiveness systematic reviews on mental health-related interventions. They identified 16 meta-analyses with at least one "large" randomized trial with sample size >800 and at least one "smaller" trial. Effect sizes were calculated separately for large and smaller trials. Heterogeneity was assessed between all studies, within each group (large and smaller studies), and between large and smaller studies. RESULTS: Significant between-study heterogeneity was seen in five meta-analyses. By random-effects calculations, the results of large and smaller trials differed beyond chance in four meta-analyses (25%). In three of these disagreements (effect of day care on IQ, discontinuation of antidepressants, risperidone versus typical antipsychotics for schizophrenia), the smaller trials showed greater effect sizes than the large trials. The inverse was seen in one case (olanzapine versus typical antipsychotics for schizophrenia). With fixed-effects models, disagreements beyond chance occurred in five cases (31%). In four meta-analyses, the effect size differed over twofold between large and smaller trials. Various quality and design parameters were identified as potential explanations for some disagreements. CONCLUSIONS: Large trials are uncommon in mental health. Their results are usually comparable with the results of smaller studies, but major disagreements do occur. Both large and smaller trials should be scrutinized as they offer a continuum of randomized evidence.
Nuclear Factor-κB Contributes to Hedgehog Signaling Pathway Activation through Sonic Hedgehog Induction in Pancreatic Cancer
Authors: Hiroshi Nakashima, Masafumi Nakamura, Hiroshi Yamaguchi, Naoki Yamanaka, Takashi Akiyoshi, Kenichiro Koga, Koji Yamaguchi, Masazumi Tsuneyoshi, Masao Tanaka, Mitsuo Katano
Journal: Cancer Research (2006)

Abstract The hedgehog (Hh) signaling pathway, which functions as an organizer in embryonic development, is implicated in the development of various tumors. In pancreatic cancer, pathway activation is reported to result from aberrant expression of the ligand, sonic Hh (Shh). However, the details of the mechanisms regulating Shh expression are not yet known. We hypothesized that nuclear factor-κB (NF-κB), a hallmark transcription factor in inflammatory responses, contributes to the overexpression of Shh in pancreatic cancer. In the present study, we found a close positive correlation between NF-κB p65 and Shh expression in surgically resected pancreas specimens, including specimens of chronic pancreatitis and pancreatic adenocarcinoma. We showed that blockade of NF-κB suppressed constitutive expression of Shh mRNA in pancreatic cancer cells. Further activation of NF-κB by inflammatory stimuli, including interleukin-1β, tumor necrosis factor-α, and lipopolysaccharide, induced overexpression of Shh, resulting in activation of the Hh pathway. Overexpression of Shh induced by these stimuli was also suppressed by blockade of NF-κB. NF-κB-induced Shh expression actually activated the Hh pathway in a ligand-dependent manner and enhanced cell proliferation in pancreatic cancer cells. In addition, inhibition of the Hh pathway as well as NF-κB suppressed the enhanced cell proliferation. Our data suggest that NF-κB activation is one of the mechanisms underlying Shh overexpression in pancreatic cancer and that proliferation of pancreatic cancer cells is accelerated by NF-κB activation in part through Shh overexpression. (Cancer Res 2006; 66(14): 7041-9)
Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study—a randomised controlled trial
Authors: Peter A Frith, Philip J Thompson, Rajeev Ratnavadivel, Catherina L Chang, Peter Bremner, Peter Day, Christina Frenzel, Nicol Kurstjens
Journal: Thorax (2015)

<h3>Background</h3> The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). <h3>Methods</h3> This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV<sub>1</sub> after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. <h3>Results</h3> 773 patients (mean FEV<sub>1</sub> 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV<sub>1</sub>: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL. There was significant increase in week 12 trough FEV<sub>1</sub> with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p&lt;0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George9s Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p&lt;0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. <h3>Conclusions</h3> GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP. <h3>Trial registration number</h3> NCT01513460.
Isolated hepatic melphalan perfusion of colorectal liver metastases: outcome and prognostic factors in 154 patients
Authors: L.B.J. van Iersel, H. Gelderblom, A.L. Vahrmeijer, E.L. van Persijn van Meerten, F.G.J. Tijl, H. Putter, H.H. Hartgrink, P.J.K. Kuppen, J.W.R. Nortier, R.A.E.M. Tollenaar, C.J.H. van de Velde
Journal: Annals of Oncology (2008)
Gene Signatures of Progression and Metastasis in Renal Cell Cancer
Authors: Jon Jones, Hasan Otu, Dimitrios Spentzos, Shakirahmed Kolia, Mehmet Inan, Wolf D. Beecken, Christian Fellbaum, Xuesong Gu, Marie Joseph, Allan J. Pantuck, Dietger Jonas, Towia A. Libermann
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC). Experimental Design: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Results: Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern (“metastatic signature”) derived from primary tumor was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described “global” metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Conclusion: Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.
Use of a T-cell interferon- release assay for the diagnosis of tuberculous pleurisy
Authors: M. Losi, A. Bossink, L. Codecasa, C. Jafari, M. Ernst, S. Thijsen, D. Cirillo, M. Ferrarese, U. Greinert, L. M. Fabbri, L. Richeldi, C. Lange
Journal: European Respiratory Journal (2007)

The diagnosis of pleural tuberculosis (plTB) by the analysis of pleural effusions (PEs) with standard diagnostic tools is difficult. In routine clinical practice, the present authors evaluated the performance of a commercially available Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot assay on peripheral blood mononuclear cells (PBMCs) and pleural effusion mononuclear cells (PEMCs) in patients with suspect plTB. The T-SPOT. TB test (Oxford Immunotec Ltd, Abingdon, UK) was performed on PBMCs and PEMCs in 20 patients with a clinical and radiological suspect of plTB and in 21 control subjects with a diagnosis of PE of nontuberculous origin at four centres participating in the European Tuberculosis Network. In total, 18 (90%) out of 20 patients with plTB tested T-SPOT. TB -positive on PBMCs and 19 (95%) out of 20 on PEMCs. Among controls, T-SPOT. TB was positive in seven out of 21 (33%) patients when performed on PBMCs (these patients were assumed to be latently infected with MTB) and five (23%) out of 21 when performed on PEMCs. Sensitivity and specificity of T-SPOT. TB for the diagnosis of active plTB when performed on PEMCs were 95 and 76%, respectively. Enumerating Mycobacterium tuberculosis -specific T-cells in pleural effusion mononuclear cells by ELISPOT is feasible in routine clinical practice and may be useful for a rapid and accurate diagnosis of pleural tuberculosis.