tbuckley/cabot-search huggingface dataset:
Tumor-Associated Macrophages in Pediatric Classical Hodgkin Lymphoma: Association with Epstein-Barr Virus, Lymphocyte Subsets, and Prognostic Impact
Authors: Mário Henrique M. Barros, Rocio Hassan, Gerald Niedobitek
Journal: Clinical Cancer Research (2012)

Tumor-infiltrating macrophages are associated with adverse outcome in adult classical Hodgkin lymphoma (cHL). We have previously shown age-related changes in the lymphocyte composition of pediatric cHL. We therefore hypothesized that the number, function, and prognostic impact of macrophages in pediatric cHL would be different from adult cases.We analyzed the number of macrophages and dendritic cells (DC) in the tumor microenvironment of pediatric cHL by immunohistochemistry. Results were analyzed in context of age, histologic characteristics, Epstein-Barr virus (EBV) status, clinical follow-up, and our previous study of T-cell populations in these cases.One hundred cHL cases were studied, including 69% nodular sclerosis and 23% mixed cellularity cases. A total of 44.8% of cases were EBV-positive. Patients ≤10 years displayed more CD14(+) cells (P = 0.025). In comparison with nodular sclerosis, mixed cellularity was characterized by higher numbers of CD14(+), (P = 0.003) and CD163(+) cells (P = 0.027). EBV(+) cases exhibited higher numbers of CD14(+) (P < 0.0005), CD68(+) (P = 0.005), and CD163(+) cells (P = 0.02). CD68-positive cells did not display an effect on outcome. Worse overall survival was observed in cases with CD163/CD8 ratio ≥2 (P = 0.007). High numbers of CD163(+) cells were associated with worse progression-free survival (PFS; P = 0.015). Furthermore, high numbers of CD163(+) and granzyme B(+) cells were associated with worse PFS in EBV-negative (P = 0.005) but not in EBV-positive cases.Our results suggest that macrophage composition in pediatric cHL is distinct from adults. Functional status of macrophages and their value as prognostic indicators in pediatric cHL may depend on EBV status.
Tuberculosis screening in Portuguese healthcare workers using the tuberculin skin test and the interferon- release assay
Authors: J. Torres Costa, R. Sa, M. J. Cardoso, R. Silva, J. Ferreira, C. Ribeiro, M. Miranda, J. L. Placido, A. Nienhaus
Journal: European Respiratory Journal (2009)

The prevalence of latent tuberculosis (TB) infection (LTBI) and the incidence of active tuberculosis in healthcare workers (HCWs) in a Portuguese hospital were examined. This cross-sectional study comprises 4,735 hospital workers screened between May 2005 and September 2008. Tuberculin skin test (TST) and interferon-gamma release assay (IGRA) were used simultaneously in 1,219 HCWs (25.7%). Radiographs were taken in symptomatic HCWs or in test-positive HCWs. The tests were repeated annually or bi-annually depending on risk assessment. IGRA was positive in 32.6% and TST in 74.2% of the HCWs. Years spent in healthcare were a risk factor for a positive IGRA, but not for a positive TST. Repeated bacillus Calmette-Guérin vaccination increased the probability of TST+/IGRA- discordance (35.4% versus 54.4%, respectively). In those tested three times with TST during the study period (n = 59), the mean diameter of TST increased from 5 to 7 to 10 mm. Within 3 yrs, 31 HCWs were diagnosed with active TB (annual incidence rate 191 out of 100,000 people). In eight HCWs with active TB, TST and IGRA were performed at the time of diagnosis and each test was positive. TB burden in HCWs in Portugal is high. With IGRA, the number of radiographs needed to exclude active TB could have been reduced by about half without missing a case of active TB. Therefore IGRA should be introduced into TB screening programmes.
Chemotherapy for Metastatic Non-Small-Cell Lung Cancer -- Can That Dog Hunt?
Authors: D. H. Johnson
Journal: JNCI Journal of the National Cancer Institute (1993)

Although no longer the most common cancer diagnosed in the United States, a dubious distinction now credited to breast cancer, bronchogenic carcinoma remains by far the principal cause of cancer-related deaths. Little progress has been made in the management of lung cancer during the past 20 years because of the systemic nature of this carcinoma and the lack of effective therapy other than surgical resection. More than 75% of patients with non-small-cell lung cancer present with unresectable disease, and even those with resectable lesions have a high propensity to experience recurrence with extrathoracic metastases. Unfortunately, an effective systemic therapy for non-small-cell lung cancer does not exist. Indeed, chemotherapy has failed to prove curative in even an occasional patient with metastatic disease. Since chemotherapy regimens used to treat metastatic non-small-cell lung cancer have no curative potential, what can one reasonably expect from them? An improvement in a patient's quality of life or a prolongation in survival would make therapy warranted. Presumably, a prolongation of life would be accompanied by a reduction in tumor-related symptoms, although this is not necessarily the case. Does chemotherapy improve the survival of non-small-cel l lung cancer patients with metastatic disease? In this issue of the Journal, Cartei et al. describe the results of a randomized phase III trial in which 102 patients with metastatic nonsmall-cell lung cancer received either supportive care or a cisplatin-based chemotherapy regimen plus supportive care (/). Supportive care consisted of analgesics, an antitussive, antibiotics, steroids, palliative radiotherapy, and the relief of increased intracranial pressure. Patients given combination chemotherapy survived a median of 8.5 months compared with just 4 months for those randomly assigned to receive supportive care alone, a difference that has high statistical significance (P<.0001). This observation is encouraging, especially because it is not the first study to demonstrate an improvement in the median survival of patients with stage IV non-small-cell lung cancer treated with chemotherapy. A well-designed Canadian trial of similar size (2) also demonstrated a doubling of the median survival for patients receiving chemotherapy. Does this mean that patients with stage IV non-small-cel l lung cancer routinely benefit from chemotherapy? Unfortunately, the answer is no. Other investigators (3-6) have conducted well-designed randomized studies with negative results.
Regulation of transforming growth factor-beta 1 gene expression by glucocorticoids in normal human T lymphocytes.
Authors: O AyanlarBatuman, A P Ferrero, A Diaz, S A Jimenez
Journal: Journal of Clinical Investigation (1991)

Glucocorticoids (GC) modulate immune function in a number of ways, including suppression of T cell proliferation and other IL-2-mediated T cell functions. These inhibitory effects are similar to those induced by transforming growth factor-beta 1 (TGF-beta 1), a cytokine with potent T cell inhibiting activities. We examined the hypothesis that GC effects may be at least partially achieved through modulation of the expression of the TGF-beta 1 gene in activated T cells. Normal T cells were cultured with or without purified phytohemagglutinin (PHA-p) and 4 beta-phorbol 12-myristate 13-acetate (PMA) in the presence or absence of the synthetic GC, dexamethasone (100-200 micrograms/ml). The production of latent and active forms of TGF beta by these cells were analyzed by immunoblotting and bioassays. The steady-state levels of TGF-beta 1 mRNA were analyzed in total RNA from these cells by Northern hybridizations using a human TGF-beta 1 cDNA. The results showed that dexamethasone caused an increase in TGF beta production and a dose-dependent two to fourfold increase in TGF-beta 1 mRNA in activated as well as in unstimulated T cells, 1 h after exposure of the cultures to the steroid. The increase in TGF-beta 1 mRNA levels by dexamethasone was further potentiated two to threefold by cycloheximide, suggesting that the steroid effect may be due to inhibition of the synthesis of proteins that decrease TGF-beta 1 gene transcription or the stability of its transcripts. Finally, in vitro nuclear transcription studies indicated the dexamethasone effects on TGF-beta 1 gene expression to be largely transcriptional.
A CRIMINOLOGIST LOOKS AT PRIVILEGE
Authors: AUSTIN MACCORMICK
Journal: American Journal of Psychiatry (1959)

The usefulness of psychiatry and acceptance of its enormous potential value in the law enforcement and correctional fields are growing steadily. The development of programs of individual and group therapy in correctional institutions seems to me the most significant thing that has happened in the correctional field in the past 40 years. Psychiatrists can speed their acceptance by fitting easily into the prison setting, and by making compromises that will make them more acceptable to old-line institution officials. I hope nothing I have said will sound as though I advocate such trimming of one's sails to the wind. In dealing with questions of privilege and in every other professional relationship, I believe unequivocally that principle, not mere practicality, should prevail. As an old hand in "the prison business," however, I do not believe they are always incompatible.
Dietary Folate Intake and Incidence of Ovarian Cancer: The Swedish Mammography Cohort
Authors: S. C. Larsson, E. Giovannucci, A. Wolk
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Mounting evidence suggests that a low intake of the water-soluble B vitamin folate is associated with breast and colorectal carcinogenesis, especially among alcohol drinkers. However, epidemiologic data specifically linking folate intake to ovarian cancer risk are limited. Methods: We examined the association between dietary folate intake (i.e., folate from food sources) and the incidence of total epithelial ovarian cancer and its subtypes by analyzing data from the Swedish Mammography Cohort, a population-based prospective cohort of 61 084 women, aged 38–76 years, who, at baseline (i.e., from 1987 to 1990), were cancer-free and had completed a food-frequency questionnaire. Through June 30, 2003, 266 incident cases of invasive epithelial ovarian cancer were diagnosed. We used Cox proportional hazards models to estimate multivariable relative risks (RRs) of ovarian cancer with 95% confidence intervals (CIs). All statistical tests were two-sided. Results: Overall, dietary folate intake was weakly inversely associated with total epithelial ovarian cancer risk (RR for highest versus lowest quartile of intake = 0.67, 95% CI = 0.43 to 1.04; Ptrend = .08). Among women who consumed more than 20 g of alcohol (approximately two drinks) per week, there was a strong inverse association between dietary folate intake and total epithelial ovarian cancer risk (RR for highest versus lowest quartile of intake = 0.26, 95% CI = 0.11 to 0.60; Ptrend = .001), but among women who consumed 20 g or less of alcohol per week, there was no such association (RR for highest versus lowest quartile of intake = 1.00, 95% CI = 0.59 to 1.70; Ptrend = .80). The absolute risk of epithelial ovarian cancer for the lowest three quartiles versus the highest quartile of folate intake was 8 per 100 000 person-years (95% CI = 0 to 16 per 100 000 person-years) overall and 26 per 100 000 person-years (95% CI = 10 to 42 per 100 000 person-years) among those who consumed more than 20 g of alcohol per week. The association between dietary folate intake and cancer risk did not vary substantially among subtypes of epithelial ovarian cancer. Conclusion: A high dietary folate intake may play a role in reducing the risk of ovarian cancer, especially among women who consume alcohol.
Medical aspects of sports injuries.
Authors: I. D. Adams
Journal: British Journal of Sports Medicine (1981)

The aims of medicine in sport--treatment and prevention of injury of high-performance athletes, rehabilitation--and its beneficial effects are considered. The types of sporting injuries are described. Collision and contact sports tend to be characterised by injuries caused by direct or indirect trauma, while athletic injuries tend to result from a variety of factors that, instead of producing excellence as intended, produce injury. The physiological changes in a top-class sportsman may also be characteristic of disease, making diagnosis of injury difficult. The importance of the sportsman's mental attitude is stressed.
Somatic FGFR3 and PIK3CA mutations are present in familial seborrhoeic keratoses
Authors: C. Hafner, T. Vogt, M. Landthaler, J. Müsebeck
Journal: British Journal of Dermatology (2008)

Seborrhoeic keratosis (SK) represents one of the most common benign skin tumours. Familial occurrence of multiple SKs has been reported, but the genetic basis of these SKs has not been investigated so far. We present a German family with at least seven affected members in two generations and occurrence of high numbers of SKs at an unusually young age, suggesting a hereditary background.Because FGFR3 and PIK3CA mutations have been reported to be involved in the pathogenesis of sporadic SK, we analysed five SKs of an affected family member for hotspot mutations of these genes.A SNaPshot multiplex assay was used for analysis of 11 previously described FGFR3 hotspot mutations. In addition, exon 9 of PIK3CA was directly sequenced and the H1047R hotspot mutation in exon 20 was analysed by a SNaPshot assay.FGFR3 mutations were present in three of five SKs. One SK with a FGFR3 mutation additionally showed a hotspot PIK3CA mutation. None of these mutations was present in the germline.The results show that this case of familial SK reveals the same mutational spectrum as sporadic SK. Because FGFR3 and PIK3CA germline mutations can be excluded as an underlying genetic basis, alternative mechanisms have to contribute to familial SK such as inherited susceptibility factors predisposing to the acquisition of somatic FGFR3 and PIK3CA mutations in skin, or increased exposure of the family members to yet unknown environmental risk factors causing these mutations.
MicroRNA 135 Is Essential for Chronic Stress Resiliency, Antidepressant Efficacy, and Intact Serotonergic Activity
Authors: Orna Issler, Sharon Haramati, Evan D. Paul, Hiroshi Maeno, Inbal Navon, Rayya Zwang, Shosh Gil, Helen S. Mayberg, Boadie W. Dunlop, Andreas Menke, Rajeshwar Awatramani, Elisabeth B. Binder, Evan S. Deneris, Christopher A. Lowry, Alon Chen
Journal: Neuron (2014)
Angiotensin II Induces Leukocyte–Endothelial Cell Interactions In Vivo Via AT <sub>1</sub> and AT <sub>2</sub> Receptor–Mediated P-Selectin Upregulation
Authors: Laura Piqueras, Paul Kubes, Angeles Alvarez, Enrique O’Connor, Andrew C. Issekutz, Juan V. Esplugues, Maria-Jesus Sanz
Journal: Circulation (2000)

Background —Angiotensin II (Ang II) plays a critical role in the development of vascular lesions in hypertension, atherosclerosis, and several renal diseases. Because Ang II may contribute to the leukocyte recruitment associated with these pathological states, the aim of the present study was to assess the role of Ang II in leukocyte–endothelial cell interactions in vivo. Methods and Results —Intravital microscopy of the rat mesenteric postcapillary venules was used. Sixty minutes of superfusion with 1 nmol/L Ang II induced a significant increase in leukocyte rolling flux (83.8±20.7 versus 16.4±3.1 cells/min), adhesion (11.4±1.0 versus 0.8±0.5 cells/100 μm), and emigration (4.0±0.7 versus 0.2±0.2 cells/field) without any vasoconstrictor activity. These effects were not mediated by mast cell activation. Intravenous pretreatment with AT 1 (losartan) or AT 2 (PD123,319) receptor antagonists significantly reduced Ang II–induced responses. A combination of both receptor antagonists inhibited the leukocyte rolling flux, adhesion, and extravasation elicited by Ang II at 60 minutes. Pretreatment of animals with fucoidin or an adhesion-blocking anti–rat P-selectin monoclonal antibody abolished Ang II–induced leukocyte responses. Furthermore, rat platelet P-selectin expression was not affected by Ang II stimulation. Conclusions —Ang II induces significant leukocyte rolling, adhesion, and emigration, which may contribute not only to hypertension but also to the onset and progression of the vascular damage associated with disease states in which plasma levels of this peptide are elevated.
Altered self-perception in adult survivors treated for a CNS tumor in childhood or adolescence: population-based outcomes compared with the general population
Authors: L. Hornquist, J. Rickardsson, B. Lannering, G. Gustafsson, K. K. Boman
Journal: Neuro-Oncology (2014)

Survivors of pediatric CNS tumors are at risk for persistent tumor/treatment-related morbidity, physical disability and social consequences that may alter self-perception, vital for self-identity, mental health and quality of survival. We studied the long-term impact of childhood CNS tumors and their treatment on the self-perception of adult survivors and compared outcomes with those of the general population.The cohort included 697 Swedish survivors diagnosed with a primary CNS tumor during 1982-2001. Comparison data were randomly collected from a stratified general population sample. Survivors and general population individuals were compared as regards self-perception in 5 domains: body image, sports/physical activities, peers, work, and family, and with a global self-esteem index. Within the survivor group, determinants of impact on self-perception were identified.The final analyzed sample included 528 survivors, 75.8% of the entire national cohort. The control sample consisted of 995, 41% of 2500 addressed. Survivors had significantly poorer self-perception outcomes in domains of peers, work, body image, and sports/physical activities, and in the global self-perception measure, compared with those of the general population (all P < .001). Within the survivor group, female gender and persistent visible physical sequelae predicted poorer outcomes in several of the studied domains. Tumor type and a history of cranial radiation therapy were associated with outcomes.An altered self-perception is a potential late effect in adult survivors of pediatric CNS tumors. Self-perception and self-esteem are significant elements of identity, mental health and quality of survival. Therefore, care and psychosocial follow-up of survivors should include measures for identifying disturbances and for assessing the need for psychosocial intervention.
Letter by Brewster and van Montfrans Regarding Article, “Risks Associated With Statin Therapy: A Systematic Overview of Randomized Clinical Trials”
Authors: Lizzy M. Brewster, Gert A. van Montfrans
Journal: Circulation (2007)

Kashani et al 1 report that in randomized trials, statin therapy (with the exclusion of cerivastatin) did not result in significant absolute increases in myalgias (risk difference per 1000 patients, 2.7 (95% CI, Ϫ3.2 to 8.7), or mild creatine kinase (CK) elevations 0.2 (95% CI, Ϫ0.6 to 0.9).The authors used data from published trials to reach this conclusion.][4][5] On the basis of the complete exclusion criteria, up to 76% of the screened participants in statin trials are not randomized and excluded. 2-5Thus, the incidence of hyperCKemia with the use of statins that emerges from these trials may mainly concern subjects in the lower part of the CK distribution, with a low a priori risk to develop highly elevated CK levels.The exclusion of these patients before randomization may lead to biased reports on the frequency of occurrence of side effects with statin use.This should be acknowledged to be a limitation when adverse effects associated with statins are assessed in published trials.
Drugs (including oxygen) in severe COPD
Authors: P. Albert, P. M. A. Calverley
Journal: European Respiratory Journal (2008)

Access to comprehensive guidelines on the management of chronic obstructive pulmonary disease (COPD) is now available, and several treatment goals of therapy have been identified from these guidelines, which have since been studied in clinical trials. Drug therapy is a key component of an individual patient’s management plan, particularly in more severe disease. During the past few years, a number of new drug treatments have become available, although these are not always appropriately prescribed; this is particularly the case for oxygen. For patients with a history of exacerbations, there is good evidence for the use of inhaled long-acting anticholinergic agents or combined inhaled steroids and long-acting β-agonists. Evidence for prophylactic antibiotics and antioxidant agents is lacking. Nutritional and calorie supplementation have not been shown to improve exercise capacity. Statins may improve outcomes in COPD, but prospective trials are needed to confirm this. The evidence for the use of long-term oxygen therapy in hypoxaemic patients is robust. Ambulatory oxygen improves exercise capacity, but whether it is used appropriately is in doubt. Overall, short burst oxygen therapy does not offer a benefit and therefore cannot be recommended.
Thrombelastography‐guided blood product use before invasive procedures in cirrhosis with severe coagulopathy
Authors: Michael J.R. Desborough, Vipul Jairath
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: The study by De Pietri et al.1 is important, given the pressing need to reduce transfusions in cirrhosis. The authors conclude that thromboelastography (TEG) can reduce transfusions for coagulopathic patients undergoing procedures and recommend reevaluation of viscoelastic test parameters for guiding transfusion. Standard coagulation measures such as the prothrombin time and activated partial thromboplastin time have little value in cirrhosis as they reflect deficiencies in procoagulant factors, without balancing concurrent deficiencies of anticoagulant factors such as antithrombin, protein C, and protein S.2 There has been a paradigm shift such that patients with cirrhosis are considered to have rebalanced hemostasis.2 A systematic review comparing patients with a prolonged international normalized ratio to those with normal coagulation indices found no difference in bleeding between the groups for patients with cirrhosis.3 TEG is a global measure of hemostasis. The R time is similar to the prothrombin time or activated partial thromboplastin time (depending on the triggering agent). Maximum amplitude is related to a combination of platelets and fibrinogen. However, TEG has similar limitations to the prothrombin time and activated partial thromboplastin time, reflecting the degree of underlying liver disease rather than bleeding risk.4 TEG also does not account for high levels of von Willebrand factor and low levels of ADAMTS13, which compensate for thrombocytopathy and thrombocytopenia in cirrhosis. Thrombin generation, another global hemostasis assay, measures the total amount of thrombin generated, rather than the amount necessary to trigger fibrin formation, and is increased in cirrhosis.4 This is likely to provide a better global assessment of coagulation in cirrhosis. In this study 47% of procedures were associated with a low risk of bleeding where transfusion should not be considered; thus, it is unclear why these patients were included in the trial design. Furthermore, the center appears to follow a liberal transfusion practice given that there was more fresh frozen plasma infused in the low‐risk compared to the high‐risk procedure group in the standard of care arm. Whether the striking treatment difference in the primary endpoint would be observed in other centers is uncertain. Overall, we suspect that the results of this study reflect that the patients with cirrhosis, even those with dramatically prolonged international normalized ratios, were not hypocoagulable (and may have been hypercoagulable). The reduction in blood component transfusions without an increase in bleeding is likely to reflect this.
Efficacy of Tumor-Targeting Salmonella Typhimurium A1-R on Highly Metastatic Human Pancreatic Cancer in Nude Mice
Authors: Robert M. Hoffman, Yukihiko Hiroshima, Ming Zhao, Ali Maawy, Yong Zhang, Fuminari Uehara, Shinji Miwa, Shuya Yano, Michael Bouvet, Itaru Endo
Journal: Annals of Oncology (2014)