tbuckley/cabot-search huggingface dataset:
Role of Lipoprotein(a) and Apolipoprotein(a) Phenotype in Atherogenesis
Authors: Florian Kronenberg, Martina F. Kronenberg, Stefan Kiechl, Evi Trenkwalder, Peter Santer, Friedrich Oberhollenzer, Georg Egger, Gerd Utermann, Johann Willeit
Journal: Circulation (1999)

Background —Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a) [Lp(a)], depending on Lp(a) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a) [apo(a)] isoforms. Epidemiological studies may contribute to assessment of the relevance of these findings in the general population. Methods and Results —This study prospectively investigated the association between Lp(a) plasma concentrations, apo(a) phenotypes, and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a random sample population of 826 individuals. We differentiated early atherogenesis (incident nonstenotic atherosclerosis) from advanced (stenotic) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms. Lp(a) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion, with this association being confined to subjects with LDL cholesterol levels above the population median (3.3 mmol/L). Apo(a) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis. In contrast, apo(a) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis, especially when associated with high Lp(a) plasma concentrations (odds ratio, 6.4; 95% CI, 2.8 to 14.9). Conclusions —Lp(a) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis. Lp(a) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol. Low-molecular-weight apo(a) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis.
Safety and effectiveness of vascular endoprosthesis for malignant superior vena cava syndrome
Authors: N P Nguyen, T L Borok, J Welsh, V Vinh-Hung
Journal: Thorax (2009)

Superior vena cava syndrome management has been traditionally radiation therapy, chemotherapy or chemoradiation, depending on the underlying malignancy involved and individual clinicopathological features of the case. Recent emergence of endovascular stents offer the opportunity for immediate relief of the venous stenosis. This review examines findings from the published series which used endovascular prosthesis for this syndrome with regards to efficacy and safety.Literature search identified studies using endovascular stents as initial therapy or for recurrence of malignant superior vena cava syndrome. Effectiveness and toxicity from stent placement was assessed.Endovascular stent placement provides immediate haemodynamic relief of venous compression either before or after definitive therapy in the majority of cancer patients. Severe bleedings, cardiopulmonary complications and stent migrations remain significant problems for patient management.Endovascular prosthesis is an effective modality for malignant superior vena cava syndrome with acceptable morbidity. Prospective studies should be performed to determine the optimal anticoagulation regimen.
Adverse Symptom Event Reporting by Patients vs Clinicians: Relationships With Clinical Outcomes
Authors: Ethan Basch, Xiaoyu Jia, Glenn Heller, Allison Barz, Laura Sit, Michael Fruscione, Mark Appawu, Alexia Iasonos, Thomas Atkinson, Shari Goldfarb, Ann Culkin, Mark G. Kris, Deborah Schrag
Journal: JNCI Journal of the National Cancer Institute (2009)

In cancer treatment trials, the standard source of adverse symptom data is clinician reporting by use of items from the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Patient self-reporting has been proposed as an additional data source, but the implications of such a shift are not understood. Patients with lung cancer receiving chemotherapy and their clinicians independently reported six CTCAE symptoms and Karnofsky Performance Status longitudinally at sequential office visits. To compare how patient's vs clinician's reports relate to sentinel clinical events, a time-dependent Cox regression model was used to measure associations between reaching particular CTCAE grade severity thresholds with the risk of death and emergency room visits. To measure concordance of CTCAE reports with indices of daily health status, Kendall tau rank correlation coefficients were calculated for each symptom with EuroQoL EQ-5D questionnaire and global question scores. Statistical tests were two-sided. A total of 163 patients were enrolled for an average of 12 months (range = 1–28 months), with a mean of 11 visits and 67 (41%) deaths. CTCAE reports were submitted by clinicians at 95% of visits and by patients at 80% of visits. Patients generally reported symptoms earlier and more frequently than clinicians. Statistically significant associations with death and emergency room admissions were seen for clinician reports of fatigue ( P < .001), nausea ( P = .01), constipation ( P = .038), and Karnofsky Performance Status ( P < .001) but not for patient reports of these items. Higher concordance with EuroQoL EQ-5D questionnaire and global question scores was observed for patient-reported symptoms than for clinician-reported symptoms. Longitudinally collected clinician CTCAE assessments better predict unfavorable clinical events, whereas patient reports better reflect daily health status. These perspectives are complementary, each providing clinically meaningful information. Inclusion of both types of data in treatment trial results and drug labels appears to be warranted.
Dissociation of Glycoprotein IIb/IIIa Antagonists From Platelets Does Not Result in Fibrinogen Binding or Platelet Aggregation
Authors: Andrew L. Frelinger, Mark I. Furman, Lori A. Krueger, Marc R. Barnard, Alan D. Michelson
Journal: Circulation (2001)

The primary mechanism of action of glycoprotein (GP) IIb/IIIa antagonists is inhibition of the final common pathway of platelet aggregation: fibrinogen binding to the GP IIb/IIIa complex. However, it has been reported that induction of fibrinogen binding and platelet aggregation is an intrinsic prothrombotic property of low-dose GP IIb/IIIa antagonists. These apparently paradoxical results have been extensively referenced in the cardiology literature.By platelet aggregation and flow cytometry, we demonstrate that (1) dissociation of GP IIb/IIIa antagonists (abciximab, tirofiban, eptifibatide, or xemilofiban) from platelets does not result in platelet aggregation; (2) tirofiban and eptifibatide can induce a fibrinogen-binding-competent conformation of the GP IIb/IIIa receptor, but stable fibrinogen binding does not occur without fixation; (3) the slow off-rate of abciximab exposes only a small proportion of unblocked GP IIb/IIIa receptors at any time, and these also fail to stably bind fibrinogen; and (4) the GP IIb/IIIa antagonist-induced fibrinogen binding in some previously reported experiments was probably the result of artifactual thrombin generation.Under physiological conditions, GP IIb/IIIa antagonists currently in clinical use do not have an intrinsic activating property that results in platelet aggregation or stable fibrinogen binding to GP IIb/IIIa.
Antigen-antibody complexes enhance the production of complement component C3 by human mesangial cells.
Authors: J J Timmerman, D J Van Gijlswijk-Janssen, S W Van Der Kooij, L A Van Es, M R Daha
Journal: Journal of the American Society of Nephrology (1997)

Deposition of immune complexes (ICX), with or without complement, occurs in various forms of glomerulonephritis. It has been reported that upregulation of complement C3 mRNA expression is found in kidneys of patients with ICX glomerulonephritis. In vitro studies have indicated that mesangial cells (MC) synthesize C3. Furthermore, MC express Fc gammaRIII receptors. This study investigates whether ICX alter C3 and factor H production by MC. MC were cultured in medium alone or in medium with insoluble heat-aggregated rat IgG (AIgG) or with insoluble ICX. Basal production of C3 and factor H was 10 +/- 1 ng/10(6) and 605 +/- 15 ng/10(6) cells, respectively. The presence of 400 microg/ml AIgG or ICX resulted in upregulation of C3 production to 999 +/- 15 ng/10(6) and 510 +/- 1 ng/10(6) cells, respectively, whereas no significant change in factor H production was observed. The upregulation of C3 was inhibitable by cycloheximide, suggesting that de novo protein synthesis was required. By reverse transcription PCR and Northern blot analysis, it was demonstrated that C3 and interleukin-6 mRNA expression was upregulated in MC after incubation with AIgG. No detectable change in factor H mRNA expression was seen. In conclusion, it is shown that incubation of MC with AIgG or ICX not only results in upregulated production of inflammatory mediators such as cytokines, but also leads to an upregulation of C3 synthesis. Therefore, it is hypothesized that ICX deposited within the mesangium may enhance the local production of C3 via interaction with Fc receptors on MC.
Barking up the wrong tree? Use of polymerase chain reaction to diagnose syphilitic aortitis
Authors: A W O'Regan
Journal: Thorax (2002)

The presentation of syphilitic aortitis is often atypical and available serological tests are non-specific. The diagnostic gold standard remains direct identification of microorganisms in tissue. We present a case of syphilitic aortitis that presented as a mediastinal mass and report the use of polymerase chain reaction for <i>Treponema pallidum</i> to diagnose syphilitic aortic disease.
Ankle-Brachial Index and Bone Turnover in Patients on Dialysis
Authors: Gérard M. London, Sylvain J. Marchais, Alain P. Guérin, Marie-Christine de Vernejoul
Journal: Journal of the American Society of Nephrology (2014)

An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH.
Indoor mite allergens in patients with respiratory allergy living in Porto, Portugal
Authors: J. L. Plácido, C. Cuesta, L. Delgado, J. P. Moreira da Silva, M. Miranda, P. Ventas, M. Vaz
Journal: Allergy (1996)

We investigated the levels of mite allergens (Der p 1, Der f 1, Der 2, and Lep d 1) in dust samples from the homes of 59 patients with asthma, 36 sensitized to house-dust mites (HDM) and 23 to grass pollen (controls), living in Porto, northern Portugal. The relationship between exposure and sensitization to HDM and the influence of housing conditions on mite-allergen levels were also evaluated. Der p 1 (median 9.2 micrograms/g) and Der 2 (4.6 micrograms/g) were the main allergens, while Der f 1 and Lep d 1 levels were always < 1 microgram/g dust and undetectable in 11% and 47% of samples, respectively. All HDM-sensitized asthmatics were exposed to Der p 1 levels > 2 micrograms/g and their homes contained significantly higher levels of Der p 1 (median 12.5 vs 6.4 micrograms/g; P = 0.008) and Der 2 (6.2 vs 3.0 micrograms/g; P = 0.004) when compared to the control group. A significant correlation was observed between the exposure to Der p 1 and the wheal area at skin testing with the Dermatophagoides pteronyssinus (Dp) extract (P = 0.01) as well as with serum specific IgE levels to Dp (P = 0.03). Patients with higher levels of serum specific IgE (> or = 17.5 HRU/ml) were also more frequently exposed to Der p 1 levels > or = 10 micrograms/g (P = 0.002). Old homes, presence of carpets, and signs of dampness were conditions associated with significantly higher levels of mite allergens. In conclusion, we found high levels of Der p 1 and Der 2 particularly in the homes of HDM-sensitized patients and we confirm the relationship between exposure and sensitization to HDM, assessed by both in vivo and in vitro methods. In additional to a favorable outdoor climate, we found in our region housing conditions propitious to mite growth, suggesting that specific geographic characteristics must also be taken into account for the correct planning of mite-avoidance measures.
Traumatic Grief Among Adolescents Exposed to a Peer’s Suicide
Authors: Nadine M Melhem, Nancy Day, M Katherine Shear, Richard Day, Charles F Reynolds, David Brent
Journal: American Journal of Psychiatry (2004)

The phenomenology of grief among children and adolescents is not well studied. A syndrome of traumatic grief, distinct from depression and anxiety, has been described among bereaved adults. The purpose of this study was to describe the symptoms and course of traumatic grief among adolescents exposed to a peer's suicide and to examine the relationship between traumatic grief and depression and posttraumatic stress disorder (PTSD) in this population.A total of 146 friends and acquaintances of 26 suicide victims were included in this study. Subjects were interviewed at 6, 12-18, and 36 months after the peer's suicide. A subgroup was also interviewed 6 years afterward. The Texas Revised Inventory of Grief was administered at 6, 12-18, and 36 months; the Inventory of Complicated Grief was administered at the 6-year assessment.Principal component analysis of the Texas Revised Inventory of Grief resulted in two factors: one assessing a traumatic grief reaction and another assessing a milder or even normal grief reaction. The occurrence of traumatic grief was found to be independent from that of depression and PTSD. Traumatic grief at 6 months predicted the onset or course of depression and PTSD at subsequent assessments.Similar to adults, adolescents experience a traumatic grief reaction after exposure to a peer's suicide. Clinicians should be alerted to the occurrence of traumatic grief reactions among adolescents and the need to assess these reactions and address them in their treatment approaches.
Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled
Authors: U. Eriksson
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To test the hypothesis that amphotericin B deoxycholate is less toxic when given by continuous infusion than by conventional rapid infusion. <b>Design:</b> Randomised, controlled, non-blinded, single centre study. <b>Setting:</b> University hospital providing tertiary clinical care. <b>Patients:</b> 80 mostly neutropenic patients with refractory fever and suspected or proved invasive fungal infections. <b>Intervention:</b> Patients were randomised to receive 0.97 mg/kg amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid infusion over four hours. <b>Main outcome measures:</b> Patients were evaluated for side effects related to infusion, nephrotoxicity, and mortality up to three months after treatment. Analysis was on an intention to treat basis. <b>Results:</b> Patients in the continuous infusion group had fewer side effects and significantly reduced nephrotoxicity than those in the rapid infusion group. Overall mortality was higher during treatment and after three months9 follow up in the rapid infusion than in the continuous infusion group. <b>Conclusion:</b> Continuous infusions of amphotericin B reduce nephrotoxicity and side effects related to infusion without increasing mortality
Null mutation in the human 11-cis retinol dehydrogenase gene associated with fundus albipunctatus11The authors have no proprietary interest in any of the materials used in this study.
Authors: Carola A.G.G Driessen, Bert P.M Janssen, Huub J Winkens, Leonoor D Kuhlmann, Anke H.M Van Vugt, Alfred J.L.G Pinckers, August F Deutman, Jacques J.M Janssen
Journal: Ophthalmology (2001)
Immune manipulation of advanced breast cancer: An interpretative model of the relationship between immune system and tumor cell biology
Authors: Andrea Nicolini, Angelo Carpi
Journal: Medicinal Research Reviews (2008)

Abstract This review summarizes some recent clinical immunological approaches with cytokines and/or antibodies for therapy of advanced breast cancer. It considers the recent advances in genetics and molecular tumor biology related to impaired immunosurveillance involving cytokines and growth factors to explain clinical results. Evasion of the host immune attack might be induced by the following groups of mechanisms: (a) tumor dependent (genomic instability, HLA class I antigen abnormalities, upregulation of fetal type nonclassical HLA class I molecules, epitope immunodominance, apoptosis inhibition by defective death receptor signaling, apoptosis of activated T cells, tumor cannibalism and constitutive activation of signal transducer, and activator of transcription‐3 (Stat 3) and nuclear factor‐κB (NF‐kB) signaling); (b) host dependent (CD4+CD25+ regulatory T cells (T reg), CD4+ T cells anergy, Th2 antitumor immunity diversion and myeloid suppressor cells); (c) tumor and host dependent (lack of co‐stimulation molecules, immunosuppressive cytokines (vascular endothelial growth factor (VEGF), interleukin (IL)‐10, prostaglandin (PG)E2, transforming growth factor (TGF)‐β)). Cytokines and growth factors are involved in virtually all three types of mechanisms. These mechanisms are integrated with the current knowledge of tumor growth and inhibited apoptosis primarily mediated by cytokines and growth factors to propose an interpretation of the relationships among tumor cells, tumor stroma, and tumor‐infiltrating lymphocytes. Tumor growth, defective immunorecognition and immunosuppression are the three principal effects considered responsible for immune evasion. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 3, 436‐471, 2009
Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study
Authors: J.B. Cwikla, A. Sankowski, N. Seklecka, J.R. Buscombe, A. Nasierowska-Guttmejer, K.G. Jeziorski, R. Mikolajczak, D. Pawlak, K. Stepien, J. Walecki
Journal: Annals of Oncology (2009)
Surgeons' leaders call for ban on cosmetic surgery advertising
Authors: A. O'Dowd
Journal: BMJ (2012)

Leading plastic surgeons have called for a complete ban on all advertising of cosmetic surgery as part of new measures to regulate the industry more closely.

The British Association of Aesthetic Plastic Surgeons published a six point plan on 23 January in which it called for steps to be taken to improve the regulation of the cosmetic industry and to protect patients’ interests.

The association, which promotes education and patient safety in cosmetic surgery, said that action was needed to combat a growth in recent years of inappropriate and aggressive marketing gimmicks that trivialised surgery.

The move comes after recent concerns over possible rupturing of breast implants made by the former French company Poly Implant Prosthese (PIP)—which closed after …
Improved Outcome With Dose-Dense Chemotherapy
Authors: Bruce Keith, Rob Hall, Aaron Scholnik
Journal: Journal of Clinical Oncology (2004)

TO THE EDITOR: Citron et al [1] have tested the hypothesis that outcome is improved with increased dose density of chemotherapy. Although it is not stated, it is likely that the dose-dense arms received considerably more granulocyte colony-stimulating factor (G-CSF) than the conventionally scheduled arms. An assumption is that G-CSF had no effect other than increasing neutrophil count and activity against infection. However, G-CSF has been found to stimulate other potentially antitumor immune functions, including chemotaxis [2], adhesion [3], pre–B cells [4], and T helper cell type 2–inducing dendritic cells [5]. G-CSF can also have an anti-inflammatory effect [6]. Inflammation is thought to play an important role in cancer, and an antiinflammatory approach to cancer treatment has been proposed [7]. Is the improved outcome due to increased dose density of chemotherapy, to increased G-CSF use, or both? To answer that question, an appropriate trial would be “dose-dense” adjuvant chemotherapy (with scheduled G-CSF) versus “standard” adjuvant chemotherapy (with scheduled G-CSF in the same dose) versus “standard” adjuvant chemotherapy (with G-CSF as clinically indicated).
Early noninvasive detection of successful reperfusion in patients with acute myocardial infarction.
Authors: A K Ellis, T Little, A R Masud, H A Liberman, D C Morris, F J Klocke
Journal: Circulation (1988)

Myoglobin (Mb) is a protein that enters rapidly and is rapidly cleared from plasma after coronary reperfusion. We sought to determine the accuracy with which a rapid rise in plasma [Mb] could predict successful coronary artery reopening in patients undergoing coronary arteriography in conjunction with attempted reperfusion in acute myocardial infarction. In 42 patients, plasma Mb levels were measured before and for at least 4 hours after attempted reperfusion. Thirty-five patients were successfully reperfused. In each, the plasma Mb level rose rapidly with peak [Mb] occurring at 111 +/- 8.1 (+/- SEM) minutes after application of therapy. In contrast, Mb levels rose more slowly in the seven patients who were not reperfused, with peak [Mb] occurring 360 +/- 61.4 minutes after attempted reperfusion. T25-100 (the time required for [Mb] to rise from 25% to 100% of peak value) was shorter in patients successfully reperfused (71 +/- 7.9 minutes) and longer (341 +/- 35.3 minutes) in patients in whom therapy was unsuccessful. A rapid rise in [Mb] after successful reperfusion was also evident by a more than 4.6-fold rise in [Mb] over the first 2 hours after reperfusion in all but five patients; in contrast, [Mb] rose by less than 4.6-fold over this same interval in every patient not successfully reperfused (sensitivity, 85%; specificity, 100%; predictive accuracy, 88%). We conclude that a rapid rise in plasma Mb level over the initial 2 hours after attempted reperfusion in acute myocardial infarction provides a useful index of successful reperfusion.
Bortezomib-thalidomide-dexamethasone (VTD) is superior to bortezomib-cyclophosphamide-dexamethasone (VCD) as induction therapy prior to autologous stem cell transplantation in multiple myeloma
Authors: M Cavo, L Pantani, A Pezzi, M T Petrucci, F Patriarca, F Di Raimondo, G Marzocchi, M Galli, V Montefusco, E Zamagni, B Gamberi, P Tacchetti, A Brioli, A Palumbo, P Sonneveld
Journal: Leukemia (2015)