tbuckley/cabot-search huggingface dataset:
Time Trends and Local Variation in Primary Treatment of Localized Prostate Cancer
Authors: Matthew R. Cooperberg, Jeanette M. Broering, Peter R. Carroll
Journal: Journal of Clinical Oncology (2010)

PURPOSE In the absence of high-level evidence or clinical guidelines supporting any given active treatment approach over another for localized prostate cancer, clinician and patient preferences may lead to substantial variation in treatment use. METHODS Data were analyzed from 36 clinical sites that contributed data to the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Distribution of primary treatment use was measured over time. Prostate cancer risk was assessed using the D'Amico risk groups and the Cancer of the Prostate Risk Assessment (CAPRA) score. Descriptive analyses were performed, and a hierarchical model was constructed that controlled for year of diagnosis, cancer risk variables, and other patient factors to estimate the proportion of variation in primary treatment selection explicable by practice site. Results Among 11,892 men analyzed, 6.8% elected surveillance, 49.9% prostatectomy, 11.6% external-beam radiation, 13.3% brachytherapy, 4.0% cryoablation, and 14.4% androgen deprivation monotherapy. Prostate cancer risk drives treatment selection, but the data suggest both overtreatment of low-risk disease and undertreatment of high-risk disease. The former trend appears to be improving over time, while the latter is worsening. Treatment varies with age, comorbidity, and socioeconomic status. However, treatment patterns vary markedly across clinical sites, and this variation is not explained by case-mix variability or known patient factors. Practice site explains a proportion of this variation ranging from 13% for androgen deprivation monotherapy to 74% for cryoablation. CONCLUSION Substantial variation exists in management of localized prostate cancer that is not explained by measurable factors. A critical need exists for high-quality comparative effectiveness research in localized prostate cancer to help guide treatment decision making.
Activation of Cancer Cell Migration and Invasion by Ectopic Synthesis of Coagulation Factor VII
Authors: Shiro Koizume, Ming-Shou Jin, Etsuko Miyagi, Fumiki Hirahara, Yoshiyasu Nakamura, Jin-Hua Piao, Akio Asai, Akira Yoshida, Eiju Tsuchiya, Wolfram Ruf, Yohei Miyagi
Journal: Cancer Research (2006)

Abstract Blood coagulation factor VII (fVII) is physiologically synthesized in the liver and released into the blood. Binding of fVII to tissue factor (TF) at sites of vascular injury triggers coagulation and hemostasis. TF/fVIIa complex formation on the surface of cancer cells plays important roles in cancer biology. Although fVII is synthesized by hepatocellular carcinoma, it remained unclear how TF/fVIIa complex formation and promigratory signaling can occur for most other cancers in extravascular locations. Here, we show by reverse transcription-PCR analysis that nonhepatic cancer cell lines constitutively express fVII mRNA and that endogenously synthesized fVIIa triggers coagulation activation on these cells. fVIIa expression in cancer cells is inducible under hypoxic conditions and hypoxia-inducible factor-2α bound the promoter region of the FVII gene in chromatin immunoprecipitation analyses. Constitutive fVII expression in an ovarian cancer cell line enhanced both migration and invasion. Enhanced motility was blocked by anti-TF antibodies, factor Xa inhibition, and anti–protease-activated receptor-1 antibody treatment, confirming that TF/fVIIa stimulated migration by triggering cell signaling. This study shows that ectopic synthesis of fVII by cancer cells is sufficient to support proinvasive factor Xa–mediated protease-activated receptor-1 signaling and that this pathway is inducible under hypoxia. (Cancer Res 2006; 66(19): 9453-60)
Bioinformatic Analysis of Circadian Gene Oscillation in Mouse Aorta
Authors: R. Daniel Rudic, Peter McNamara, Dermot Reilly, Tilo Grosser, Anne-Marie Curtis, Thomas S. Price, Satchidananda Panda, John B. Hogenesch, Garret A. FitzGerald
Journal: Circulation (2005)

Background— Circadian rhythmicity of many aspects of cardiovascular function—blood pressure, coagulation and contractile function—is well established, as is diurnal variation in important clinical events, such as myocardial infarction and stroke. Here, we undertake studies to globally assess circadian gene expression in murine aorta. Methods and Results— Aortae from mice were harvested at 4-hour intervals for 2 circadian cycles (48 hours). Gene expression was assessed by expression profiling and subjected to a gene ontology bioinformatics analysis. Three hundred thirty transcripts exhibited a circadian pattern of oscillation in mouse aorta, including those intrinsic to the function of the molecular clock. In addition, many genes relevant to protein folding, protein degradation, glucose and lipid metabolism, adipocyte maturation, vascular integrity, and the response to injury are also included in this subset of roughly 7000 genes screened for circadian oscillation. Conclusions— Detection of functional cassettes of vascular genes that exhibit circadian regulation in the mouse will facilitate elucidation of the mechanisms by which the molecular clock may interact with environmental variables to modulate cardiovascular function and the response to therapeutic interventions.
Kaposi-like acroangiodermatitis in an above-knee amputation stump
Authors: G. KOLDE, J. WORHEIDE, R. BAUMGARTNER, EVA-B. BROCKER
Journal: British Journal of Dermatology (1989)

The clinical, histological and immunohistological features of a Kaposi‐like acroangiodermatitis in an above‐knee amputation stump are reported. There was no evidence for an underlying arteriovenous malformation and the irregular purple‐blue skin lesions resulted from chronic circulatory disturbance of the distal stump caused by a poorly fitting suction‐type prosthesis.
Community-acquired pneumonia in younger patients is an entity on its own
Authors: Benjamin Klapdor, Santiago Ewig, Mathias W. Pletz, Gernot Rohde, Hartwig Schütte, Tom Schaberg, Tobias Welte
Journal: European Respiratory Journal (2011)

Community-acquired pneumonia (CAP) is now most frequent in elderly patients. CAP in the younger patient has attracted much less attention. Therefore, we compared patients with CAP aged 18 to &lt;65 yrs with those aged ≥65 yrs. Data from the prospective multicentre Competence Network for Community Acquired Pneumonia Study Group (CAPNETZ) database were analysed for potential differences in baseline characteristics, comorbidities, clinical presentation, microbial investigations, aetiologies, antimicrobial treatment and outcomes. Overall, 7,803 patients were studied. The proportion of younger patients (aged &lt;65 yrs) was 52.3% (18 to &lt;30 yrs 6.4%; &lt;40 yrs 17.1%; &lt;50 yrs 29.4%). Comorbidity was present in only half of the younger patients (46.6% versus 88.2%). Fever and chest pain were more common. Most younger patients presented with mild CAP (74.0% had a CURB-65 score of 0 (confusion of new onset, urea &gt;7 mmol·L −1 , respiratory rate of ≥30 breaths·min −1 , blood pressure &lt;90 mmHg or diastolic blood pressure ≤60 mmHg, age ≥65 yrs)). Overall, Streptococcus pneumoniae and Mycoplasma pneumoniae were the most frequent pathogens in the younger patients. Short-term mortality was very low (1.7% versus 8.2%) and even lower in patients without comorbidity (0.3% versus 2.4%). Long-term mortality was 3.2% versus 15.9%, also lower in patients without comorbidity (0.8% versus 6.1%). Most of the differences found clearly arise after the fifth or within the middle of the sixth decade. CAP in the younger patient is a clinically distinct entity.
Cloned cytotoxic T lymphocytes that recognize an I-A region product in the context of a class I antigen.
Authors: N Shinohara, J A Bluestone, D H Sachs
Journal: The Journal of Experimental Medicine (1986)

Cloned CTLs QM3 and QM7 isolated from a bulk CTL line B10.QBR anti-B10.MBR recognized a combination of the H-2Kb molecule and an I-Ak subregion gene product. Such a combinatorial specificity was revealed by complementation of the target antigen in F1 animals between two negative parental strains carrying H-2Kb and I-Ak, respectively. We confirmed the involvement of the H-2Kb molecule by blocking killing with anti-Kb mAb and failure of certain mutant H-2Kb genes to complement with I-Ak to generate the determinant in F1 animals. Although the nature of the I-Ak subregion gene product is not definitive, there was a correlation between the expression of Ia antigens on the cell surface and susceptibility of the cells to lysis by these CTLs, suggesting that it is the classical I-Ak class II antigen.
Activation of Sphingosine-1-Phosphate 1 Receptor in the Proximal Tubule Protects Against Ischemia-Reperfusion Injury
Authors: Amandeep Bajwa, Sang-Kyung Jo, Hong Ye, Liping Huang, Krishna R. Dondeti, Diane L. Rosin, Volker H. Haase, Timothy L. Macdonald, Kevin R. Lynch, Mark D. Okusa
Journal: Journal of the American Society of Nephrology (2010)

Agonists of the sphingosine-1-phosphate receptor (S1PR) attenuate kidney ischemia-reperfusion injury (IRI). Previous studies suggested that S1P1R-induced lymphopenia mediates this protective effect, but lymphocyte-independent mechanisms could also contribute. Here, we investigated the effects of S1PR agonists on kidney IRI in mice that lack T and B lymphocytes (Rag-1 knockout mice). Administration of the nonselective S1PR agonist FTY720 or the selective S1P1R agonist SEW2871 reduced injury in both Rag-1 knockout and wild-type mice. In vitro, SEW2871 significantly attenuated LPS- or hypoxia/reoxygenation-induced apoptosis in cultured mouse proximal tubule epithelial cells, supporting a direct protective effect of S1P1R agonists via mitogen-activated protein kinase and/or Akt pathways. S1P1Rs in the proximal tubule mediated IRI in vivo as well: Mice deficient in proximal tubule S1P1Rs experienced a greater decline in renal function after IRI than control mice and their kidneys were no longer protected by SEW2871 administration. In summary, S1PRs in the proximal tubule are necessary for stress-induced cell survival, and S1P1R agonists are renoprotective via direct effects on the tubule cells. Selective agonists of S1P1Rs may hold therapeutic potential for the prevention and treatment of acute kidney injury.
Chitin Particles Are Multifaceted Immune Adjuvants
Authors: Carla A. Da Silva, Pierre Pochard, Chun Geun Lee, Jack A. Elias
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Chitin is a ubiquitous polysaccharide in fungi, insects, allergens, and parasites that is released at sites of infection. Its role in the generation of tissue inflammation, however, is not fully understood.We hypothesized that chitin is an important adjuvant for adaptive immunity.Mice were injected with a solution of ovalbumin and chitin.We used in vivo and ex vivo/in vitro approaches to characterize the ability of chitin fragments to foster adaptive immune responses against ovalbumin and compared these responses to those induced by aluminum hydroxide (alum). In vivo, ovalbumin challenge caused an eosinophil-rich pulmonary inflammatory response, Th2 cytokine elaboration, IgE induction, and mucus metaplasia in mice that had been sensitized with ovalbumin plus chitin or ovalbumin plus alum. Toll-like receptor-2, MyD88, and IL-17A played critical roles in the chitin-induced responses, and MyD88 and IL-17A played critical roles in the alum-induced responses. In vitro, CD4(+) T cells from mice sensitized with ovalbumin plus chitin were incubated with ovalbumin-stimulated bone marrow-derived dendritic cells. In these experiments, CD4(+) T-cell proliferation, IL-5, IL-13, IFN-γ, and IL-17A production were appreciated. Toll-like receptor-2, MyD88, and IL-17A played critical roles in these in vitro adjuvant properties of chitin. TLR-2 was required for cell proliferation, whereas IL-17 and TLR-2 were required for cytokine elaboration. IL-17A also inhibited the generation of adaptive Th1 responses.These studies demonstrate that chitin is a potent multifaceted adjuvant that induces adaptive Th2, Th1, and Th17 immune responses. They also demonstrate that the adjuvant properties of chitin are mediated by a pathway(s) that involves and is regulated by TLR-2, MyD88, and IL-17A.
Patterns of Survival Among Patients With Myeloproliferative Neoplasms Diagnosed in Sweden From 1973 to 2008: A Population-Based Study
Authors: Malin Hultcrantz, Sigurdur Yngvi Kristinsson, Therese M.-L. Andersson, Ola Landgren, Sandra Eloranta, Åsa Rangert Derolf, Paul W. Dickman, Magnus Björkholm
Journal: Journal of Clinical Oncology (2012)

Reported survival in patients with myeloproliferative neoplasms (MPNs) shows great variation. Patients with primary myelofibrosis (PMF) have substantially reduced life expectancy, whereas patients with polycythemia vera (PV) and essential thrombocythemia (ET) have moderately reduced survival in most, but not all, studies. We conducted a large population-based study to establish patterns of survival in more than 9,000 patients with MPNs.We identified 9,384 patients with MPNs (from the Swedish Cancer Register) diagnosed from 1973 to 2008 (divided into four calendar periods) with follow-up to 2009. Relative survival ratios (RSRs) and excess mortality rate ratios were computed as measures of survival.Patient survival was considerably lower in all MPN subtypes compared with expected survival in the general population, reflected in 10-year RSRs of 0.64 (95% CI, 0.62 to 0.67) in patients with PV, 0.68 (95% CI, 0.64 to 0.71) in those with ET, and 0.21 (95% CI, 0.18 to 0.25) in those with PMF. Excess mortality was observed in patients with any MPN subtype during all four calendar periods (P < .001). Survival improved significantly over time (P < .001); however, the improvement was less pronounced after the year 2000 and was confined to patients with PV and ET.We found patients with any MPN subtype to have significantly reduced life expectancy compared with the general population. The improvement over time is most likely explained by better overall clinical management of patients with MPN. The decreased life expectancy even in the most recent calendar period emphasizes the need for new treatment options for these patients.
Interleukin-17 cytokine signalling in patients with asthma
Authors: Anders Lindén, Barbro Dahlén
Journal: European Respiratory Journal (2014)

Asthma remains a global health problem and, therefore, more effective pharmacotherapy is needed. This is particularly true for chronic and severe asthma. In these clinical phenotypes, chronic inflammation involving neutrophils is likely to play a pathogenic role, making it interesting to target cytokine signalling involved in the accumulation of neutrophils. Therefore, it is of interest that the archetype T-helper 17 cell cytokine interleukin (IL)-17A, perhaps also IL-17F, controls neutrophil accumulation, mucus secretion, macrophage mobilisation and smooth muscle reactivity in various experimental airway models. However, much less is known about the involvement of signalling via IL-17 cytokines in humans with asthma. Existing evidence suggests that these cytokines are released from several types of immune cells in asthma and, for IL-17A, there is a local increase associated with disease severity, with the mobilisation of neutrophils and smooth muscle cells locally in the airways. Even though the causative role of IL-17 cytokines remains unclear, there is potential for clinical utility in targeting IL-17A specifically in patients with moderate-to-severe asthma and high reversibility. There is a need for new and well-powered clinical investigations of signalling via IL-17 cytokines in this clinical phenotype.
Impact of Tic Disorders on ADHD Outcome Across the Life Cycle: Findings From a Large Group of Adults With and Without ADHD
Authors: T J Spencer, J Biederman, S Faraone, E Mick, B Coffey, D Geller, J Kagan, S K Bearman, T Wilens
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The impact of tic disorders on the outcome of attention deficit hyperactivity disorder (ADHD) remains a subject of high scientific and clinical interest. To evaluate the impact of comorbid ADHD and tic disorders from a lifespan perspective, the authors systematically examined data from adults with and without ADHD. METHOD: They comprehensively evaluated 312 consecutively referred adults with ADHD and 252 comparison subjects without ADHD. Tic disorders were characterized along with a wide range of neuropsychiatric correlates, including other comorbid disorders as well as indexes of function in the domains of school, cognition, and interpersonal functioning. RESULTS: A significantly greater proportion of adults with ADHD (12%) than those without ADHD (4%) had tic disorders. Tic disorders followed a mostly remitting course and had little impact on functional capacities. In addition, tic disorders were not associated with stimulant use. CONCLUSIONS: These findings in adults with ADHD confirm and extend previous findings in young subjects with ADHD, documenting that although individuals with ADHD are at greater risk for tic disorders, the presence of tic disorders has a limited impact on ADHD outcome.
Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomized, placebo-controlled safety and efficacy study of imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and liver transplant patients
Authors: C. Ulrich, J. Bichel, S. Euvrard, B. Guidi, C.M. Proby, P.C.M. Van De Kerkhof, P. Amerio, J. Rønnevig, H.B. Slade, E. Stockfleth
Journal: British Journal of Dermatology (2007)

Objective In this study the safety and efficacy of imiquimod 5% cream for the treatments of actinic keratoses in kidney, heart and liver transplant recipients is evaluated. Background Growing populations of organ transplant recipients face increased risk of developing actinic keratosis (AK) and skin cancer secondary to continuous systemic immunosuppressive therapy. Imiquimod 5% cream is an effective option for the treatment of AK, but the safety of topical immune stimulation in immunocompromised patients has not been widely evaluated. Methods A total of 43 patients in six European transplant centres applied two sachets of topical imiquimod or vehicle cream three times per week to a 100 cm2 field. Dosing continued for 16 weeks regardless of lesion clearance. Patients were assessed for safety variables that included adverse events, local skin reactions, laboratory results, vital signs, dosage of immunosuppressive medication and indication of graft rejection. A blinded independent expert committee was responsible for safety monitoring and final safety assessment. Results No graft rejections or trends for a deterioration of graft function were detected. No meaningful trends were observed in laboratory results. Among patients randomized to imiquimod, the complete clearance rate was 62·1% (18/29); for vehicle patients, the complete clearance rate was 0% (0/14). Clinical clearance was confirmed histologically in all cases. Conclusions Imiquimod appears to be a safe alternative for the treatment of multiple actinic keratoses in patients with solid organ transplants. Efficacy was within the range previously observed in nontransplanted populations.
Time Course of Functional Recovery of Stunned and Hibernating Segments After Surgical Revascularization
Authors: J J Bax, F C Visser, D Poldermans, A Elhendy, J H Cornel, E Boersma, A van Lingen, P M Fioretti, C A Visser
Journal: Circulation (2001)

Recovery of function is possible in patients with ischemic cardiomyopathy when left ventricular dysfunction is caused by stunning or hibernation. It is plausible that recovery of function after revascularization may take a longer time in hibernating myocardium compared with stunned myocardium. Accordingly, the time courses of functional recovery in hibernating and stunned myocardium were compared.Patients (n=26) with ischemic cardiomyopathy undergoing surgical revascularization were studied; regional perfusion (resting (201)Tl single-photon emission CT), glucose utilization ((18)F-2-deoxyglucose single-photon emission CT), and contractile function (2D echocardiography) were assessed before revascularization. Dysfunctional segments with normal perfusion/glucose utilization were considered to be stunned, and dysfunctional segments with reduced perfusion/preserved glucose utilization were considered to be hibernating. Contractile function was reevaluated 3 months (early) and 14 months (late) after revascularization. Of the 266 dysfunctional segments, 57 (22%) were stunned, 62 (23%) were hibernating, and 147 (55%) were scar tissue. In stunned myocardium, contractile function improved significantly at 3 months, without further improvement at 14 months; 61% of the stunned segments improved at 3 months, and 9% improved at 14 months. In hibernating myocardium, contractile function improved at 3 months, with a further improvement at 14 months; 31% of the hibernating segments improved at 3 months, and 61% showed (additional) recovery at 14 months.Stunned myocardium is likely to demonstrate early recovery of function, whereas hibernating myocardium may take a longer time to (fully) recover in function after revascularization.
Analysis of current data on the use of methotrexate in the treatment of pemphigus and pemphigoid
Authors: H.M. Gürcan, A. Razzaque Ahmed
Journal: British Journal of Dermatology (2009)

Methotrexate (MTX) is primarily used in the treatment of malignancies. It has also been used as an immunosuppressive agent in the treatment of pemphigus and pemphigoid. The objective of this study was to determine the role of MTX in the treatment of pemphigus and pemphigoid based on an analysis of the available literature. A retrospective analysis of the English language literature was conducted. The studies included in this analysis were required to fulfil the following inclusion criteria: English language; diagnosis based on histology and immunopathology; minimum of five patients in each series; and data for efficacy, spectrum of responses and follow-up. A total of 136 patients with pemphigus were reported in seven studies. One hundred and eleven of the 136 patients (82%) showed clinical improvement with MTX. A total of 79 patients with pemphigoid were reported in six studies. Overall, 74 of the 79 patients (94%) showed clinical improvement. Nausea and infection were the most common side-effects. Death due to MTX resulted in seven of 215 patients (3%). There is a lack of randomized controlled trials. In many studies in this review there was insufficient information on clinical follow-up post-therapy and on serological correlations. Analysis of the data suggests that MTX may be useful and effective in patients with pemphigus vulgaris, who are corticosteroid dependent or who develop significant complications in relation to corticosteroids. MTX is likely to be more beneficial in patients with pemphigoid, particularly in bullous pemphigoid, than in patients with pemphigus. Given the limitations of the available data, it appears that when there is a need for adjuvant therapy, MTX may be considered early in the management of moderate to moderately severe disease.