tbuckley/cabot-search huggingface dataset:
Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care?
Authors: R. Raine
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To determine the strength of evidence for the effectiveness of mental health interventions for patients with three common somatic conditions (chronic fatigue syndrome, irritable bowel syndrome, and chronic back pain). To assess whether results obtained in secondary care can be extrapolated to primary care and suggest how future trials should be designed to provide more rigorous evidence. <b>Design:</b> Systematic review. <b>Data sources:</b> Five electronic databases, key texts, references in the articles identified, and citations from expert clinicians. <b>Study selection:</b> Randomised controlled trials including participants with one of the three conditions for which no physical cause could be found. Two reviewers screened sources and independently extracted data and assessed quality. <b>Results:</b> Sixty one studies were identified; 20 were classified as primary care and 41 as secondary care. For some interventions, such as brief psychodynamic interpersonal therapy, little research was identified. However, results of meta-analyses and of randomised controlled trials suggest that cognitive behaviour therapy and behaviour therapy are effective for chronic back pain and chronic fatigue syndrome and that antidepressants are effective for irritable bowel syndrome. Cognitive behaviour therapy and behaviour therapy were effective in both primary and secondary care in patients with back pain, although the evidence is more consistent and the effect size larger for secondary care. Antidepressants seem effective in irritable bowel syndrome in both settings but ineffective in chronic fatigue syndrome. <b>Conclusions:</b> Treatment seems to be more effective in patients in secondary care than in primary care. This may be because secondary care patients have more severe disease, they receive a different treatment regimen, or the intervention is more closely supervised. However, conclusions of effectiveness should be considered in the light of the methodological weaknesses of the studies. Large pragmatic trials are needed of interventions delivered in primary care by appropriately trained primary care staff. <h3>What is already known on this topic</h3> Patients with functional somatic symptoms are common in primary care and may not receive effective mental health interventions <h3>What this study adds</h3> Research in secondary and primary care shows that cognitive behaviour therapy and behaviour therapy help patients with back pain and that antidepressants benefit patients with irritable bowel syndrome Effect sizes are larger in secondary care than in primary care Patients in secondary care with chronic fatigue syndrome may benefit from cognitive behaviour therapy Future research should focus on large pragmatic trials with longer term follow up and economic evaluation
Biophysical Cues and Cell Behavior: The Big Impact of Little Things
Authors: Joshua Z. Gasiorowski, Christopher J. Murphy, Paul F. Nealey
Journal: Annual Review of Biomedical Engineering (2013)

The extracellular matrix is composed of a variety of proteins, polysaccharides, and glycosaminoglycans that self-assemble into a hierarchical order of nanometer- to micrometer-scale fibrils and fibers. The shapes, sizes, and elasticity present within this highly ordered meshwork regulate behaviors in most cell types. It has been well documented that cellular migration, proliferation, differentiation, and tissue development are all influenced by matrix geometries and compliance, but how these external biophysical cues are translated into activated intracellular signaling cascades remains poorly understood. Fortunately, technological improvements in artificial substrate fabrication have provided biologists with tools to test cellular interactions within controlled three-dimensional environments. Here, we review cellular responses to biophysical cues and discuss their clinical relevancy and application. We focus especially on integrative approaches that aim to first characterize the properties of specific extracellular matrices and then precisely fabricate biomimetic materials to elucidate how relevant cells respond to the individual biophysical cues present in their native tissues. Through these types of comprehensive studies, biologists have begun to understand and appreciate how exceedingly small features can have a significant impact on the regulation, development, and homeostasis of cells and tissues.
URTICARIA PIGMENTOSA IN ADULTS. *
Authors: M. G. HANNAY
Journal: British Journal of Dermatology (1925)

Journal Article URTICARIA PIGMENTOSA IN ADULTS. Get access M. G. HANNAY, M.D., M.R.C.P. M. G. HANNAY, M.D., M.R.C.P. Late Hon. Physician, St. John's Hospital for Diseases of the Skin Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 1, 1 January 1925, Pages 1–13, https://doi.org/10.1111/j.1365-2133.1925.tb09214.x Published: 01 January 1925
Amino-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein as Predictors of Sudden Cardiac Death Among Women
Authors: Ethan C. Korngold, James L. Januzzi, Mary Lou Gantzer, M.V. Moorthy, Nancy R. Cook, Christine M. Albert
Journal: Circulation (2009)

Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been found to predict risk of sudden cardiac death (SCD) in patients with known cardiac disease, and C-reactive protein levels have been found to predict risk among apparently healthy men. However, there are no data on SCD risk prediction for either of these markers in a population of women unselected on the basis of cardiovascular disease.In a prospective, nested, case-control analysis within the 121,700-participant Nurses' Health Study, 99 cases of definite or probable SCD were identified and matched to 294 controls. In multivariable models that adjusted for coronary heart disease risk factors, glomerular filtration rate, and other biomarkers, the trend across quartiles approached significance for NT-proBNP (rate ratio=2.37 for comparison of the highest and lowest quartile; P for trend=0.05) but not for high-sensitivity C-reactive protein (P for trend=0.60). When examined continuously, both NT-proBNP and high-sensitivity C-reactive protein were significantly associated with SCD risk in age- and fasting-adjusted models (P for linear trend=0.04 and 0.03). Adjustment for coronary heart disease risk factors and other biomarkers strengthened the relationship with NT-proBNP and SCD (relative risk for 1-SD increment=1.49; 95% confidence interval, 1.09 to 2.05; P=0.01) but eliminated the relationship with high-sensitivity C-reactive protein (P=0.34). Women with NT-proBNP levels above the prespecified cut point of 389 pg/mL were at a markedly increased risk of SCD in both models (rate ratio=5.68; 95% confidence interval, 1.78 to 18.2; P=0.003).In this population of women, baseline levels of NT-proBNP were associated with subsequent risk of SCD. If this association is confirmed in larger prospectively studied populations, these findings might provide another useful marker contributing to efforts to screen and prevent SCD among women.
Long-term mortality among adults with or without asthma in the PAARC study
Authors: S. Vandentorren, I. Baldi, I. Annesi Maesano, D. Charpin, F. Neukirch, L. Filleul, A. Cantagrel, J.F. Tessier
Journal: European Respiratory Journal (2003)

The Pollution Atmosphérique et Affections Respiratoires Chroniques (PAARC; Air Pollution and Chronic Respiratory Diseases) study provided the opportunity to examine the 25-yr mortality of 940 asthmatic adults drawn from a large population-based sample of 14,267 adults investigated during 1974–1976 in seven French cities. Vital statistics were collected in 2001 for the whole population. Multivariate survival analysis was used to assess exact survival rates in asthmatics and nonasthmatics taking relevant confounders into account. On average, the mortality rates obtained were 10.4 and 6.9 deaths·1,000 person-yrs<sup>−1</sup> in asthmatics and nonasthmatics, respectively. On univariate analysis, asthma increased the relative risk (RR) of death by 1.48 (95% confidence interval (CI) 1.29–1.69). The association between asthma and death had an RR of 1.16 (95% CI 0.99–1.37) when age, sex, educational level, smoking habits, occupational exposure and forced expiratory volume in one second (FEV<sub>1</sub>) were taken into account. FEV<sub>1</sub> was an important contributive factor causing increased risk of death in both smokers and nonsmokers. For instance, in asthmatics, the numbers of deaths due to respiratory disease and cancer appeared excessive. The present study suggests that asthmatics exhibit a higher risk of mortality.
Rheumatological diseases and cancer: the hidden variable of radiation exposure
Authors: Eugenio Picano, Richard Semelka, James Ravenel, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2014)

Understanding the mechanisms of host macrophage responses to <i>Mycobacterium tuberculosis</i> is essential for uncovering potential avenues of intervention to boost host resistance to infection. Macrophage transcriptome profiling revealed that <i>M. tuberculosis</i> infection strongly induced the expression of several enzymes controlling tryptophan catabolism. These included IDO1 and tryptophan 2,3-dioxygenase, which catalyze the rate-limiting step in the kynurenine pathway, producing ligands for the aryl hydrocarbon receptor (AHR). The AHR and heterodimeric partners AHR nuclear translocator and RELB are robustly expressed, and AHR and RELB levels increased further during infection. Infection enhanced AHR/AHR nuclear translocator and AHR/RELB DNA binding and stimulated the expression of AHR target genes, including that encoding the inflammatory cytokine IL-1β. AHR target gene expression was further enhanced by exogenous kynurenine, and exogenous tryptophan, kynurenine, or synthetic agonist indirubin reduced mycobacterial viability. Comparative expression profiling revealed that AHR ablation diminished the expression of numerous genes implicated in innate immune responses, including several cytokines. Notably, AHR depletion reduced the expression of <i>IL23A</i> and <i>IL12B</i> transcripts, which encode subunits of IL-23, a macrophage cytokine that stimulates production of IL-22 by innate lymphoid cells. AHR directly induced <i>IL23A</i> transcription in human and mouse macrophages through near-upstream enhancer regions. Taken together, these findings show that AHR signaling is strongly engaged in <i>M. tuberculosis</i>–infected macrophages and has widespread effects on innate immune responses. Moreover, they reveal a cascade of AHR-driven innate immune signaling, because IL-1β and IL-23 stimulate T cell subsets producing IL-22, another direct target of AHR transactivation.
Randomized Study of Paclitaxel and Tamoxifen Deposition into Human Brain Tumors: Implications for the Treatment of Metastatic Brain Tumors
Authors: Robert L. Fine, Johnson Chen, Casilda Balmaceda, Jeffrey N. Bruce, May Huang, Manisha Desai, Michael B. Sisti, Guy M. McKhann, Robert R. Goodman, Joseph S. Bertino, Anne N. Nafziger, Michael R. Fetell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Drug resistance in brain tumors is partially mediated by the blood-brain barrier of which a key component is P-glycoprotein, which is highly expressed in cerebral capillaries. Tamoxifen is a nontoxic inhibitor of P-glycoprotein. This trial assessed, in primary and metastatic brain tumors, the differential deposition of paclitaxel and whether tamoxifen could increase paclitaxel deposition. Experimental Design: Patients for surgical resection of their primary or metastatic brain tumors were prospectively randomized to prior paclitaxel alone (175 mg/m2/i.v.) or tamoxifen for 5 days followed by paclitaxel. Central and peripheral tumor, surrounding normal brain and plasma, were analyzed for paclitaxel and tamoxifen. Results: Twenty-seven patients completed the study. Based on a multivariate linear regression model, no significant differences in paclitaxel concentrations between the two study arms were found after adjusting for treatment group (tamoxifen versus control). However, in analysis for tumor type, metastatic brain tumors had higher paclitaxel concentrations in the tumor center (1.93-fold, P = 0.10) and in the tumor periphery (2.46-fold, P = 0.039) compared with primary brain tumors. Pharmacokinetic analyses showed comparable paclitaxel areas under the serum concentration between treatment arms. Conclusions: Paclitaxel deposition was not increased with this tamoxifen schedule as the low plasma concentrations were likely secondary to concurrent use of P-450-inducing medications. However, the statistically higher paclitaxel deposition in the periphery of metastatic brain tumors provides functional evidence corroborating reports of decreased P-glycoprotein expression in metastatic versus primary brain tumors. This suggests that metastatic brain tumors may respond to paclitaxel if it has proven clinical efficacy for the primary tumor's histopathology.
Peptide Epitopes from the Wilms' Tumor 1 Oncoprotein Stimulate CD4+ and CD8+ T Cells That Recognize and Kill Human Malignant Mesothelioma Tumor Cells
Authors: Rena J. May, Tao Dao, Javier Pinilla-Ibarz, Tatyana Korontsvit, Victoriya Zakhaleva, Rong H. Zhang, Peter Maslak, David A. Scheinberg
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Wilms' tumor 1 protein (WT1), a transcription factor overexpressed in malignant mesothelioma, leukemias, and other solid tumors, is an ideal target for immunotherapy. WT1 class I peptide epitopes that were identified and shown to stimulate CD8+ T cells are being tested as vaccine candidates in several clinical trials. The induction and maintenance of a robust memory CD8+ cytotoxic T-cell response requires CD4+ T-cell help. Experimental Design: Three HLA class II peptide epitopes of WT1 with high predictive affinities to multiple HLA-DRB1 molecules were identified using the SYFPEITHI algorithm. Due to the highly polymorphic nature of the HLA class II alleles, such reactivity is critical in the development of a broadly useful therapeutic. One of the WT1 CD4+ peptide epitopes, 122-140, comprises a previously identified CD8+ peptide epitope (126-134). By mutating residue 126 from an arginine to a tyrosine, we embedded a synthetic immunogenic analogue CD8+ epitope (126-134) inside the longer peptide (122-140). This analogue was previously designed to improve immunogenicity and induce a potent CD8+ response. Results: WT1 peptides 328-349 and 423-441 are able to stimulate a peptide-specific CD4+ response that can recognize WT1+ tumor cells in multiple HLA-DRB1 settings as determined by IFN-γ enzyme-linked immunospot assays. The mutated WT1 peptide epitope 122-140 is able to induce CD4+ and cytotoxic CD8+ WT1-specific T-cell responses that can recognize the native WT1 epitopes on the surface of human WT1+ cancer cells. Cross-priming experiments showed that antigen-presenting cells pulsed with either mesothelioma or leukemia tumor lysates can process and present each of the CD4+ peptides identified. Conclusions: These studies provide the rationale for using the WT1 CD4+ peptides in conjunction with CD8+ peptide epitopes to vaccinate patients with WT1-expressing cancers.
DOXORUBICIN-INDUCED CARDIOTOXICITY IN MICE IS BLUNTED BY LATE SODIUM CURRENT INHIBITION WITH RANOLAZINE, WITH IMPROVEMENT IN HEART FUNCTION, FIBROSIS AND APOPTOSIS
Authors: Nicola Maurea, Carmela Coppola, Giovanna Piscopo, Clemente Cipresso, Domenica Rea, Aldo Giudice, Carlo Maurea, Claudio Arra, Claudia De Lorenzo, Carlo Gabriele Tocchetti
Journal: Journal of the American College of Cardiology (2013)
Comparison of Three Management Strategies for Patients With Atypical Squamous Cells of Undetermined Significance: Baseline Results From a Randomized Trial
Authors: D. Solomon, M. Schiffman, R. Tarone
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: More than 2 million U.S. women receive an equivocal cervical cytologic diagnosis (atypical squamous cells of undetermined significance [ASCUS]) each year. Effective colposcopy triage strategies are needed to identify the minority of women who have clinically significant disease while avoiding excessive follow-up evaluation for others. Methods: The ASCUS/LSIL (i.e., low-grade squamous intraepithelial lesion) Triage Study (ALTS) is a multicenter, randomized trial comparing the sensitivity and specificity of the following three management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3): 1) immediate colposcopy (considered to be the reference standard), 2) triage to colposcopy based on human papillomavirus (HPV) results from Hybrid Capture 2™ (HC 2) and thin-layer cytology results, or 3) triage based on cytology results alone. This article summarizes the cross-sectional enrollment results for 3488 women with a referral diagnosis of ASCUS. All statistical tests are two-sided. Results: Among participants with ASCUS, the underlying prevalence of histologically confirmed CIN3 was 5.1%. Sensitivity to detect CIN3 or above by testing for cancer-associated HPV DNA was 96.3% (95% confidence interval [CI] = 91.6% to 98.8%), with 56.1% of women referred to colposcopy. Sensitivity of a single repeat cytology specimen with a triage threshold of HSIL or above was 44.1% (95% CI = 35.6% to 52.9%), with 6.9% referred. Sensitivity of a lower cytology triage threshold of ASCUS or above was 85.3% (95% CI = 78.2% to 90.8%), with 58.6% referred. Conclusions: HC 2 testing for cancer-associated HPV DNA is a viable option in the management of women with ASCUS. It has greater sensitivity to detect CIN3 or above and specificity comparable to a single additional cytologic test indicating ASCUS or above.
Inhibition of Collagen Receptor Discoidin Domain Receptor-1 (DDR1) Reduces Cell Survival, Homing, and Colonization in Lung Cancer Bone Metastasis
Authors: Karmele Valencia, Cristina Ormazábal, Carolina Zandueta, Diego Luis-Ravelo, Iker Antón, María J. Pajares, Jackeline Agorreta, Luis M. Montuenga, Susana Martínez-Canarias, Birgit Leitinger, Fernando Lecanda
Journal: Clinical Cancer Research (2012)

We investigated the role of the collagen-binding receptor discoidin domain receptor-1 (DDR1) in the initiation and development of bone metastasis.We conducted immunohistochemical analyses in a cohort of 83 lung cancer specimens and examined phosphorylation status in a panel of human lung cancer cell lines. Adhesion, chemotaxis, invasiveness, metalloproteolytic, osteoclastogenic, and apoptotic assays were conducted in DDR1-silenced cells. In vivo, metastatic osseous homing and colonization were assessed in a murine model of metastasis.DDR1 was expressed in a panel of human lung cancer cell lines, and high DDR1 levels in human lung tumors were associated with poor survival. Knockdown (shDDR1) cells displayed unaltered growth kinetics in vitro and in vivo. In contrast, shDDR1 cells showed reduced invasiveness in collagen matrices and increased apoptosis in basal conditions and induced apoptosis in vitro. More importantly, conditioned media of DDR1-knockdown cells decreased osteoclastogenic activity in vitro. Consequently, in a model of tumor metastasis to bone, lack of DDR1 showed decreased metastatic activity associated with reduced tumor burden and osteolytic lesions. These effects were consistent with a substantial reduction in the number of cells reaching the bone compartment. Moreover, intratibial injection of shDDR1 cells significantly decreased bone tumor burden, suggesting impaired colonization ability that was highly dependent on the bone microenvironment.Disruption of DDR1 hampers tumor cell survival, leading to impaired early tumor-bone engagement during skeletal homing. Furthermore, inhibition of DDR1 crucially alters bone colonization. We suggest that DDR1 represents a novel therapeutic target involved in bone metastasis.
Supervised Preventive Therapy for Latent Tuberculosis Infection in Illegal Immigrants in Italy
Authors: ALBERTO MATTEELLI, CATERINA CASALINI, MARIO C. RAVIGLIONE, ISSA EL-HAMAD, CARLA SCOLARI, ENRICO BOMBANA, MASSIMILIANO BUGIANI, MARIA CAPUTO, CARMELO SCARCELLA, GIAMPIERO CAROSI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In a multicenter, prospective, randomized, open-label study of isoniazid-preventive therapy (IPT) for latent tuberculosis infection, illegal immigrants from countries where tuberculosis is highly endemic were enrolled at two clinical sites in Northern Italy. Of 208 eligible subjects, 82 received supervised IPT at a dose of 900 mg twice weekly for 6 mo (Regimen A), 73 received unsupervised IPT 900 mg twice weekly for 6 mo (Regimen B), and 53 received unsupervised IPT 300 mg daily for 6 mo (Regimen C). Supervised IPT was delivered at either one tuberculosis clinic or one migrant clinic. The probability of completing a 26-wk regimen was 7, 26, and 41% in Regimens A, B, and C, respectively (p < 0.005, Log- rank test calculated using Kaplan-Meier plots). The mean time to dropout was 3.8, 6, and 6.2 wk in Regimens A, B, and C, respectively (p = 0.003 for regimen A versus either Regimens B or C). Treatment was stopped in five subjects (2.4%) because of adverse events. The rate of completion of preventive therapy for latent tuberculosis infection among illegal immigrants was low. Supervised, clinic-based administration of IPT significantly reduced adherence. Alternative strategies to implement preventive therapy in illegal immigrants are clearly required.
Humanized Radioiodinated Minibody For Imaging of Prostate Stem Cell Antigen–Expressing Tumors
Authors: Jeffrey V. Leyton, Tove Olafsen, Eric J. Lepin, Scott Hahm, Karl B. Bauer, Robert E. Reiter, Anna M. Wu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Prostate stem cell antigen (PSCA) is a cell surface glycoprotein that is overexpressed in prostate cancer, including hormone refractory disease. Previous preclinical studies showed the intact anti-PSCA antibodies, 1G8 and hu1G8, localized specifically to PSCA-expressing xenografts. Optimal micro positron emission tomography (microPET) imaging using hu1G8, however, required a delay of 168 hours postinjection. In this study, the 2B3 minibody (an 80-kDa engineered antibody fragment) has been produced for rapid targeting and imaging. Experimental Design: A gene encoding a PSCA-specific minibody, VL-linker-VH-hinge-huIgG1 CH3, was assembled. The minibody was expressed by secretion from mammalian cells and purified by cation exchange chromatography. Relative affinity and specificity were determined by competition ELISA and flow cytometry. Serial microPET imaging using a 124I-labeled minibody was conducted at 4 and 21 hours in mice bearing LAPC-9 AD, LAPC-9 AI, PC-3, and LNCaP-PSCA human prostate cancer xenografts. Tumor and tissue biodistribution was determined, and region of interest analysis of the images was conducted. Results: Yields of 20 mg/L purified 2B3 minibody were obtained that showed specific binding to LNCaP-PSCA cells. Purified 2B3 minibody showed specific binding to LNCaP-PSCA cells with an apparent affinity of 46 nmol/L. Radioiodinated 2B3 minibody showed rapid nontarget tissue and blood clearance kinetics (t1/2β = 11.2 hours). MicroPET scanning using the 124I-2B3 minibody showed both androgen-dependent and -independent tumors as early as 4 hours and excellent high contrast images at 21 hours postinjection. Conclusions: Imaging PSCA-positive prostate cancer is feasible using an intermediate size antibody fragment at 21 hours.