tbuckley/cabot-search huggingface dataset:
Remarks on Dr. Herbert Davies's Method of Treating Acute Rheumatism
Authors: W. O. Markham
Journal: BMJ (1865)

DAVIEs recommends a new method* of treating acute rheumatic fever; viz., " exclusively by free blistering.He has lately systematically pur- sued this plan in the London Hospital.The treat- ment is absolutely local, without the aid of " alkalies, nitre, leimon-juice, bark, opium, colchicum, or, in fact, any of the internal remedies which are and have been considered as specific in that affection."The result, Dr. Davies says, is in all respects highly satisfactory.His theory of rheumatism is the ordi- narily accepted one, that there exists in the system a materies morbi, consisting either of an excess of some normal element, or of a new product, intensely acid, and highly irritating to synovial alnd fibrous tissues.
Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis
Authors: L C Doward, A Spoorenberg, S A Cook, D Whalley, P S Helliwell, L J Kay, S P McKenna, A Tennant, D van der Heijde, M A Chamberlain
Journal: Annals of the Rheumatic Diseases (2002)

<b>Background:</b> Although disease-specific health status measures are available for ankylosing spondylitis (AS), no instrument exists for assessing quality of life (QoL) in the condition. <b>Objective:</b> To produce an AS-specific QoL measure that would be relevant and acceptable to respondents, valid, and reliable. <b>Methods:</b> The ASQoL employs the needs-based model of QoL and was developed in parallel in the UK and the Netherlands (NL). Content was derived from interviews with patients in each country. Face and content validity were assessed through patient field test interviews (UK and NL). A postal survey in the UK produced a more efficient version of the ASQoL, which was tested for scaling properties, reliability, internal consistency, and validity in a further postal survey in each country. <b>Results:</b> A 41 item questionnaire was derived from interview transcripts. Field testing interviews confirmed acceptability. Rasch analysis of data from the first survey (n=121) produced a 26 item questionnaire. Rasch analysis of data from the second survey (UK: n=164; NL: n=154) showed some item misfit, but showed that items formed a hierarchical order and were stable over time. Problematic items were removed giving an 18 item scale. Both language versions had excellent internal consistency (α=0.89–0.91), test-retest reliability (<i>r</i><sub>s</sub>=0.92 UK and <i>r</i><sub>s</sub>=0.91 NL), and validity. <b>Conclusions:</b> The ASQoL provides a valuable tool for assessing the impact of interventions for AS and for evaluating models of service delivery. It is well accepted by patients, taking about four minutes to complete, and has excellent scaling and psychometric properties.
Radioactive yttrium in the treatment of rheumatoid knee effusions. Preliminary evaluation.
Authors: J F Bridgman, F Bruckner, N M Bleehen
Journal: Annals of the Rheumatic Diseases (1971)

Irradiation of the synovium for the treatment of chronic knee effusions associated with rheumatoid arthritis and allied conditions is being increasingly used as an alternative to surgical synovectomy.Intra- articular injections of a colloidal solution of radio- active gold (19"8Au) has been tried with some success (Ansell, Crook, Mallard, and Bywaters, 1963; Virkkunen, Krusius, and Heiskanen, 1967; Makin and Robin, 1968; Grahame, Ramsey, and Scott, 1970).However, as 198Au has a beta-particle maximum range in tissue of only 4 mm.and as the synovium in these chronic knee effusions can attain a thickness of greater than 1 cm., a complete synovial ablation is not produced.A serious disadvantage of intra- articular 198Au is that there may be marked leakage from the joint to the regional lymph nodes, the liver, and spleen in as many as 36 per cent. of patients so treated (Virkkunnen and others, 1967).Moreover, radioactive gold possesses a significant gamma-ray component and this gives an unwanted whole body radiation to the patient.Because of these disadvantages it has been suggested that radioactive yttrium (90Y) may be a more suitable agent (Ansell and others, 1963; Grahame and others, 1970).90Y is a pure beta-emitter with a maximum range in tissue of 10 mm.It has a higher maximum energy than gold, 2 26 MeV compared with 0 9 MeV, and it has a half-life of 2-7 days.The whole body distribution of 90Y silicate and 90Y resin after intra- articular injections has been compared (Prichard, Bridgman, and Bleehen, 1970).It was found that silicate preparations were associated with an appreciable leakage from the joint, but that the resin remained localized.It has also been shown that the 90Y resin was taken up more or less evenly in both normal and inflamed rabbit synovia (Webb, Lowe, and Bluestone, 1969).
Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition
Authors: Gordon S. Doig, Fiona Simpson, Elizabeth A. Sweetman, Simon R. Finfer, D. Jamie Cooper, Philippa T. Heighes, Andrew R. Davies, Michael O’Leary, Tom Solano, Sandra Peake
Journal: JAMA (2013)

Systematic reviews suggest adult patients in intensive care units (ICUs) with relative contraindications to early enteral nutrition (EN) may benefit from parenteral nutrition (PN) provided within 24 hours of ICU admission.To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes.Multicenter, randomized, single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zealand. Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days.Random allocation to pragmatic standard care or early PN.Day-60 mortality; quality of life, infections, and body composition.A total of 1372 patients were randomized (686 to standard care, 686 to early PN). Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4). Patients receiving early PN commenced PN a mean of 44 minutes after enrollment (95% CI, 36 to 55). Day-60 mortality did not differ significantly (22.8% for standard care vs 21.5% for early PN; risk difference, -1.26%; 95% CI, -6.6 to 4.1; P = .60). Early PN patients rated day-60 quality of life (RAND-36 General Health Status) statistically, but not clinically meaningfully, higher (45.5 for standard care vs 49.8 for early PN; mean difference, 4.3; 95% CI, 0.95 to 7.58; P = .01). Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference, -0.47; 95% CI, -0.82 to -0.11; P = .01) and, based on Subjective Global Assessment, experienced less muscle wasting (0.43 vs 0.27 score increase per week; mean difference, -0.16; 95% CI, -0.28 to -0.038; P = .01) and fat loss (0.44 vs 0.31 score increase per week; mean difference, -0.13; 95% CI, -0.25 to -0.01; P = .04).The provision of early PN to critically ill adults with relative contraindications to early EN, compared with standard care, did not result in a difference in day-60 mortality. The early PN strategy resulted in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays.anzctr.org.au Identifier: ACTRN012605000704695.
Fluoroquinolones: are they essential to treat multidrug-resistant tuberculosis?
Authors: G. B. Migliori, C. Lange, E. Girardi, R. Centis, G. Besozzi, K. Kliiman, L. R. Codecasa, A. Spanevello, D. M. Cirillo
Journal: European Respiratory Journal (2008)

To the Editors: 

We read with interest the excellent letter by Holtz and Cegielski 1 contributing to the current discussion on extensively drug-resistant (XDR)-tuberculosis (TB). Several publications have already demonstrated that resistance to fluoroquinolones (FQ) is independently associated with poor outcome and/or that the possibility of including FQ in regimens improves treatment outcomes of multidrug-resistant (MDR)-TB cases 2–4. This happened before the (recent) description of XDR-TB 1, 5. We do not know how many of the patients with MDR-TB strains were, in fact, infected with XDR Mycobacterium tuberculosis .

We wanted to establish the role of the different XDR-defining components ( e.g. isoniazid and rifampicin, FQ and injectable second-line drugs) in determining poor treatment outcomes.

Our group has shown for the first time that XDR-TB cases in Italy and Germany have a five-fold increase in the risk of death (relative risk (RR) 5.45; 95% …
Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma
Authors: Valerie Chew, Jinmiao Chen, Deming Lee, Evelyn Loh, Joyce Lee, Kiat Hon Lim, Achim Weber, Ksenija Slankamenac, Ronnie T P Poon, Henry Yang, London Lucien P J Ooi, Han Chong Toh, Mathias Heikenwalder, Irene O L Ng, Alessandra Nardin, Jean-Pierre Abastado
Journal: Gut (2011)

Hepatocellular carcinoma (HCC) is a heterogeneous disease with poor prognosis and limited methods for predicting patient survival. The nature of the immune cells that infiltrate tumours is known to impact clinical outcome. However, the molecular events that regulate this infiltration require further understanding. Here the ability of immune genes expressed in the tumour microenvironment to predict disease progression was investigated.Using quantitative PCR, the expression of 14 immune genes in resected tumour tissues from 57 Singaporean patients was analysed. The nearest-template prediction method was used to derive and test a prognostic signature from this training cohort. The signature was then validated in an independent cohort of 98 patients from Hong Kong and Zurich. Intratumoural components expressing these critical immune genes were identified by in situ labelling. Regulation of these genes was analysed in vitro using the HCC cell line SNU-182.The identified 14 immune-gene signature predicts patient survival in both the training cohort (p=0.0004 and HR=5.2) and the validation cohort (p=0.0051 and HR=2.5) irrespective of patient ethnicity and disease aetiology. Importantly, it predicts the survival of patients with early disease (stages I and II), for whom classical clinical parameters provide limited information. The lack of predictive power in late disease stages III and IV emphasises that a protective immune microenvironment has to be established early in order to impact disease progression significantly. This signature includes the chemokine genes CXCL10, CCL5 and CCL2, whose expression correlates with markers of T helper 1 (Th1), CD8(+) T and natural killer (NK) cells. Inflammatory cytokines (tumour necrosis factor α, interferon γ) and Toll-like receptor 3 ligands stimulate intratumoural production of these chemokines which drive tumour infiltration by T and NK cells, leading to enhanced cancer cell death.A 14 immune-gene signature, which identifies molecular cues driving tumour infiltration by lymphocytes, accurately predicts survival of patients with HCC especially in early disease.
<i>ATM, CTLA4, MNDA</i>, and<i>HEM1</i>in High versus Low CD38–Expressing B-Cell Chronic Lymphocytic Leukemia
Authors: Avadhut D. Joshi, Ganapati V. Hegde, John D. Dickinson, Amit K. Mittal, James C. Lynch, James D. Eudy, James O. Armitage, Philip J. Bierman, R. Gregory Bociek, Marcel P. Devetten, Julie M. Vose, Shantaram S. Joshi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In B-cell chronic lymphocytic leukemia (CLL), high CD38 expression has been associated with unfavorable clinical course, advanced disease, resistance to therapy, shorter time to first treatment, and shorter survival. However, the genes associated with CLL patient subgroups with high and low CD38 expression and their potential role in disease progression is not known. Experimental Design: To identify the genes associated with the clinical disparity in CLL patients with high versus low CD38 expression, transcriptional profiles were obtained from CLL cells from 39 different patients using oligonucleotide microarray. Gene expression was also compared between CLL cells and B cells from healthy individuals. Results: Gene expression analysis identified 76 differentially expressed genes in CD38 high versus low groups. Out of these genes, HEM1, CTLA4, and MNDA were selected for further studies and their differential expression was confirmed by real-time PCR. HEM1 overexpression was associated with poor outcome, whereas the overexpression of CTLA4 and MNDA was associated with good outcome. Down-regulation of HEM1 expression in patient CLL cells resulted in a significant increase in their susceptibility to fludarabine-mediated killing. In addition, when gene expression patterns in CD38 high and low CLL cells were compared with normal B-cell profiles, ATM expression was found to be significantly lower in CD38 high compared with CD38 low CLL as confirmed by real-time reverse transcription-PCR. Conclusions: These results identify the possible genes that may be involved in cell proliferation and survival and, thus, determining the clinical behavior of CLL patients expressing high or low CD38.
Avoiding backward steps in COPD: looking again at roflumilast
Authors: E. D. Bateman, K. F. Rabe, P. M. A. Calverley, U. M. Goehring, M. Brose, D. Bredenbroker, L. Fabbri
Journal: European Respiratory Journal (2011)

addressing several other mechanisms and comorbidities in COPD.
Compliance for NIMV treatment in moderate and severe OSAS patients
Authors: Hatice Kutbay Özçelik, Ersan Atahan, Muhammed Emin Akkoyunlu, Mehmet Bayram, Fatmanur Karaköse, Murat Sezer, Levent Kart
Journal: European Respiratory Journal (2012)

Aim: In the non-invasive mechanic ventilation (NIMV) using in the treatment of obstructive sleep apnea syndrome (OSAS), compliance problem is a frequently seen difficulty. Aim in this study is to analyze the compliance of the OSAS patients to the NIMV treatment, and to search the factors affecting the compliance.  Method: The patients given NIMV treatment in the sleep laboratory of the university hospital due to moderate or severe OSAS between 1 January 2011 and 31 December 2011 were included to our study. Polisomnographic findings of the patients were recorded. A questionnaire about compliance to the NIMV that had been set by our clinic applied to the patients by the phone calls.  Results: 75,4% of the 134 included patients were male. The mean age was 49,9±12,3. Mean BMI, Epworth and RDI of the patients were 32,55±5,9, 10,6 ±6,0 and 43± 23,1. Complication related to the NIMV device use was seen in 37 (27%) of the patients. The most frequently seen complications were dryness of mouth, discomfort due to mask, dryness of throat, irritation of the eyes, nasal congestion, bloating, claustrophobia and headache. Sixteen (11,9%) patients was not using the NIMV device due to device discordance. Six of these patients have severe, and 10 of these patients have moderate OSAS.  Conclusion: Compliance to the NIMV in the OSAS treatment is still an important problem. Patients treated with NIMV should be kept under close observation and should be informed about the risks of the disease if not used the device.
Human Osteocalcin and Bone Sialoprotein Mediating Osteomimicry of Prostate Cancer Cells: Role of cAMP-Dependent Protein Kinase A Signaling Pathway
Authors: Wen-Chin Huang, Zhihui Xie, Hiroyuki Konaka, Jaro Sodek, Haiyen E. Zhau, Leland W.K. Chung
Journal: Cancer Research (2005)

Abstract Osteocalcin and bone sialoprotein are the most abundant noncollagenous bone matrix proteins expressed by osteoblasts. Surprisingly, osteocalcin and bone sialoprotein are also expressed by malignant but not normal prostate epithelial cells. The purpose of this study is to investigate how osteocalcin and bone sialoprotein expression is regulated in prostate cancer cells. Our investigation revealed that (a) human osteocalcin and bone sialoprotein promoter activities in an androgen-independent prostate cancer cell line of LNCaP lineage, C4-2B, were markedly enhanced 7- to 12-fold in a concentration-dependent manner by conditioned medium collected from prostate cancer and bone stromal cells. (b) Deletion analysis of human osteocalcin and bone sialoprotein promoter regions identified cyclic AMP (cAMP)–responsive elements (CRE) as the critical determinants for conditioned medium–mediated osteocalcin and bone sialoprotein gene expression in prostate cancer cells. Consistent with these results, the protein kinase A (PKA) pathway activators forskolin and dibutyryl cAMP and the PKA pathway inhibitor H-89, respectively, increased or repressed human osteocalcin and bone sialoprotein promoter activities. (c) Electrophoretic mobility shift assay showed that conditioned medium–mediated stimulation of human osteocalcin and bone sialoprotein promoter activities occurs through increased interaction between CRE and CRE-binding protein. (d) Conditioned medium was found to induce human osteocalcin and bone sialoprotein promoter activities via increased CRE/CRE-binding protein interaction in a cell background–dependent manner, with marked stimulation in selected prostate cancer but not bone stromal cells. Collectively, these results suggest that osteocalcin and bone sialoprotein expression is coordinated and regulated through cAMP-dependent PKA signaling, which may define the molecular basis of the osteomimicry exhibited by prostate cancer cells.
Vancomycin-Induced Immune Thrombocytopenia
Authors: Annette Von Drygalski, Brian R. Curtis, Daniel W. Bougie, Janice G. McFarland, Scott Ahl, Indra Limbu, Kelty R. Baker, Richard H. Aster
Journal: New England Journal of Medicine (2007)

Vancomycin has only rarely been implicated as a cause of thrombocytopenia, and there is only limited evidence that this complication is caused by immune mechanisms. We conducted a study to determine whether thrombocytopenia is caused by vancomycin-dependent antibodies in patients being treated with vancomycin.We identified and characterized vancomycin-dependent, platelet-reactive antibodies in patients who had been referred for testing during a 5-year period because of a clinical suspicion of vancomycin-induced thrombocytopenia. We obtained clinical information about the patients from their referring physicians.Drug-dependent, platelet-reactive antibodies of the IgG class, the IgM class, or both were identified in 34 patients, and clinical follow-up information was obtained from 29 of these patients. The mean nadir platelet count in these patients was 13,600 per cubic millimeter, and severe bleeding occurred in 10 patients (34%). Platelet levels returned to baseline in all 26 surviving patients after vancomycin was stopped. In 15 patients, the drug was continued for 1 to 14 days while other possible causes of thrombocytopenia were investigated. Vancomycin-dependent antibodies were not found in 25 patients who had been given vancomycin and in whom thrombocytopenia did not develop.Severe bleeding can occur in patients with vancomycin-induced immune thrombocytopenia. The detection of vancomycin-dependent antiplatelet antibodies in patients receiving the antibiotic in whom thrombocytopenia develops, and the absence of antibodies in patients given the drug in whom platelet counts remain stable, indicate that these antibodies are the cause of the thrombocytopenia.
Astrocyte Elevated Gene-1 Interacts with Akt Isoform 2 to Control Glioma Growth, Survival, and Pathogenesis
Authors: Bin Hu, Luni Emdad, Manny D. Bacolod, Timothy P. Kegelman, Xue-Ning Shen, Mohammad A. Alzubi, Swadesh K. Das, Devanand Sarkar, Paul B. Fisher
Journal: Cancer Research (2014)

Abstract The oncogene astrocyte elevated gene-1 (AEG-1; MTDH) is highly expressed in glioblastoma multiforme (GBM) and many other types of cancer, where it activates multiple signaling pathways that drive proliferation, invasion, angiogenesis, chemoresistance, radioresistance, and metastasis. AEG-1 activates the Akt signaling pathway and Akt and c-Myc are positive regulators of AEG-1 transcription, generating a positive feedback loop between AEG-1 and Akt in regulating tumorigenesis. Here, we describe in GBM cells a direct interaction between an internal domain of AEG-1 and the PH domain of Akt2, a major driver in GBM. Expression and interaction of AEG-1 and Akt2 are elevated in GBM and contribute to tumor cell survival, proliferation, and invasion. Clinically, in silico gene expression and immunohistochemical analyses of patient specimens showed that AEG-1 and Akt2 expression correlated with GBM progression and reduced patient survival. AEG-1–Akt2 interaction prolonged stabilization of Akt2 phosphorylation at S474, regulating downstream signaling cascades that enable cell proliferation and survival. Disrupting AEG-1–Akt2 interaction by competitive binding of the Akt2-PH domain led to reduced cell viability and invasion. When combined with AEG-1 silencing, conditional expression of Akt2-PH markedly increased survival in an orthotopic mouse model of human GBM. Our study uncovers a novel molecular mechanism by which AEG-1 augments glioma progression and offers a rationale to block AEG-1–Akt2 signaling function as a novel GBM treatment. Cancer Res; 74(24); 7321–32. ©2014 AACR.
Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer patients: acute toxicity analyses from the French multicentric study
Authors: Y. Belkacémi, J. Gligorov, M. Ozsahin, H. Marsiglia, B. De Lafontan, H. Laharie-Mineur, L. Aimard, E.-C. Antoine, B. Cutuli, M. Namer, D. Azria
Journal: Annals of Oncology (2008)
Sensitization to the Lysosomal Cell Death Pathway by Oncogene-Induced Down-regulation of Lysosome-Associated Membrane Proteins 1 and 2
Authors: Nicole Fehrenbacher, Lone Bastholm, Thomas Kirkegaard-Sørensen, Bo Rafn, Trine Bøttzauw, Christina Nielsen, Ekkehard Weber, Senji Shirasawa, Tuula Kallunki, Marja Jäättelä
Journal: Cancer Research (2008)

Abstract Expression and activity of lysosomal cysteine cathepsins correlate with the metastatic capacity and aggressiveness of tumors. Here, we show that transformation of murine embryonic fibroblasts with v-H-ras or c-srcY527F changes the distribution, density, and ultrastructure of the lysosomes, decreases the levels of lysosome-associated membrane proteins (LAMP-1 and LAMP-2) in an extracellular signal-regulated kinase (ERK)- and cathepsin-dependent manner, and sensitizes the cells to lysosomal cell death pathways induced by various anticancer drugs (i.e., cisplatin, etoposide, doxorubicin, and siramesine). Importantly, K-ras and erbb2 elicit a similar ERK-mediated activation of cysteine cathepsins, cathepsin-dependent down-regulation of LAMPs, and increased drug sensitivity in human colon and breast carcinoma cells, respectively. Notably, reconstitution of LAMP levels by ectopic expression or by cathepsin inhibitors protects transformed cells against the lysosomal cell death pathway. Furthermore, knockdown of either lamp1 or lamp2 is sufficient to sensitize the cells to siramesine-induced cell death and photo-oxidation–induced lysosomal destabilization. Thus, the transformation-associated ERK-mediated up-regulation of cysteine cathepsin expression and activity leads to a decrease in the levels of LAMPs, which in turn contributes to the enhanced sensitivity of transformed cells to drugs that trigger lysosomal membrane permeabilization. These data indicate that aggressive cancers with high cysteine cathepsin levels are especially sensitive to lysosomal cell death pathways and encourage the further development of lysosome-targeting compounds for cancer therapy. [Cancer Res 2008;68(16):6623–33]
Mycobacterium avium infection of the skin resembling lepromatous leprosy
Authors: GARY W. COLE, JOHN GEBHARD
Journal: British Journal of Dermatology (1979)

A patient on systemic steroid therapy developed a cutaneous papule which histologically resembled lepromatous leprosy. Cultures of this lesion grew Mycobacterium avium. Since there was no evidence of disseminated infection the lesion was excised and the patient continues to do well.