tbuckley/cabot-search huggingface dataset:
Abstract P5-13-01: Does empowering patients improve accrual to breast cancer trials?
Authors: A Arnaout, I Kuchuk, N Bouganim, S Verma, M Clemons
Journal: Cancer Research (2012)

Abstract BACKGROUND Many international oncology professional and patient advocacy groups recommend that a minimum of 5% of eligible new patients should be entered into a clinical trial. Unfortunately, physician and patient related barriers translates to a much lower accrual rate in reality. We performed a prospective single arm pilot study evaluating the efficacy of implementing various physician and patient related strategies in enhancing clinical trial accrual. METHODS All patients with newly diagnosed breast cancer seen at the breast surgery clinic were eligible for the study. Patients were offered information packages by their surgeons on non-surgical clinical trials that they might be eligible for, prior to their initial oncologist visit. Oncologists were informed of the information given to the prospective patient consultation via email and chart flagging. Patient were then given a questionnaire assessing the feedback on this method of introducing clinical trials. The primary outcome was the number of patients consenting to clinical trials. Secondary outcomes included the number of patients actually enrolling in clinical trials, screen failure rate, and overall patient satisfaction with this method of potentially enhancing accrual to clinical trials. RESULTS 36 patients consented to this pilot study. 51% of oncologists mentioned the clinical trials to the patients. For those patients with which clinical trials were discussed, 72% went on to consent for a trial of which 31% were ultimately found to be ineligible (screen failure rate). The overall 14% clinical trial enrolment was significantly higher than our historical average of 7%. 100% of the patients found that the information package very helpful and was noted to reduce anxiety (39%) and empower (31%) the patients. 19% of the patients felt that this information should have been offered by the oncologist during the initial consultation as opposed to the surgeon prior to the oncology visit. CONCLUSIONS The findings of this study could have a major impact on the way that cancer centres across the world approach patients for clinical trial options. Physicians remain an important barrier to trial accrual. The results of this study demonstrate that combined patient and physician centered approach to clinical trial enrolment may be the most effective. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-13-01.
High-mobility group box 1 activates caspase-1 and promotes hepatocellular carcinoma invasiveness and metastases
Authors: Wei Yan, Ying Chang, Xiaoyan Liang, Jon S. Cardinal, Hai Huang, Stephen H. Thorne, Satdarshan P.S. Monga, David A. Geller, Michael T. Lotze, Allan Tsung
Journal: Hepatology (2012)

Hypoxia is often found in solid tumors and is associated with tumor progression and poor clinical outcomes. The exact mechanisms related to hypoxia-induced invasion and metastasis remain unclear. We elucidated the mechanism by which the nuclear-damage–associated molecular pattern molecule, high-mobility group box 1 (HMGB1), released under hypoxic stress, can induce an inflammatory response to promote invasion and metastasis in hepatocellular carcinoma (HCC) cells. Caspase-1 activation was found to occur in hypoxic HCC cells in a process that was dependent on the extracellular release of HMGB1 and subsequent activation of both Toll-like receptor 4 (TLR4)- and receptor for advanced glycation endproducts (RAGE)-signaling pathways. Downstream from hypoxia-induced caspase-1 activation, cleavage and release of proinflammatory cytokines interleukin (IL)-1β and -18 occurred. We further demonstrate that overexpression of HMGB1 or treatment with recombinant HMGB1 enhanced the invasiveness of HCC cells, whereas stable knockdown of HMGB1 remarkably reduced HCC invasion. Moreover, in a murine model of HCC pulmonary metastasis, stable knockdown of HMGB1 suppressed HCC invasion and metastasis. Conclusion: These results suggest that in hypoxic HCC cells, HMGB1 activates TLR4- and RAGE-signaling pathways to induce caspase-1 activation with the subsequent production of multiple inflammatory mediators, which, in turn, promote cancer invasion and metastasis. (HEPATOLOGY 2012;55:1866–1875)
B-Type Natriuretic Peptide Predicts Sudden Death in Patients With Chronic Heart Failure
Authors: Rudolf Berger, Martin Huelsman, Karin Strecker, Anja Bojic, Petra Moser, Brigitte Stanek, Richard Pacher
Journal: Circulation (2002)

Given the high incidence of sudden death in patients with chronic heart failure (CHF) and the efficacy of implantable cardioverter-defibrillators, an appropriate tool for the prediction of sudden death is desirable. B-type natriuretic peptide (BNP) has prognostic significance in CHF, and the stimuli for its production cause electrophysiological abnormalities. This study tests BNP levels as a predictor of sudden death.BNP levels, in addition to other neurohormonal, clinical, and hemodynamic variables, were obtained from 452 patients with a left ventricular ejection fraction (LVEF) < or =35%. For prediction of sudden death, only survivors without heart transplantation (HTx) or a mechanical assist device and patients who died suddenly were analyzed. Up to 3 years, 293 patients survived without HTx or a mechanical assist device, 89 patients died, and 65 patients underwent HTx. Mode of death was sudden in 44 patients (49%), whereas 31 patients (35%) had pump failure and 14 patients (16%) died from other causes. Univariate risk factors of sudden death were log BNP (P=0.0006), log N-terminal atrial natriuretic peptide (P=0.003), LVEF (P=0.005), log N-terminal BNP (P=0.006), systolic blood pressure (P=0.01), big endothelin (P=0.03), and NYHA class (P=0.04). In the multivariate model, log BNP level was the only independent predictor of sudden death (P=0.0006). Using a cutoff point of log BNP <2.11 (130 pg/mL), Kaplan-Meier sudden death-free survival rates were significantly higher in patients below (99%) compared with patients above (81%) this cutoff point (P=0.0001).BNP levels are a strong, independent predictor of sudden death in patients with CHF.
P16.31 * THERANOSTIC APPLICATION OF WATER-SOLUBLE GADOLINIUM FULLERENE (GD@FUL) IN EXPERIMENTAL GLIOMA MODEL
Authors: M. Shevtsov, B. Nikolaev, Y. Marchenko, L. Yakovleva, A. Dobrodumov, G. Torok, E. Pitkin, V. Lebedev
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GMB) is a highly invasive brain tumour with poor prognosis. Alternative treatments offering a better outcome are needed. Novel approach could be based on gadofullerenes that can be used as diagnostic MR imaging contrast agent and as a therapeutic drug. Water soluble gadofullerene Gd@Ful with composition Gd@C82(OH)x x ≥20 was synthesized for theranostic study. Nanosuspensions of Gd@Ful were used for magnetic relaxation measurements in vitro and for MR imaging of a rat with intracranially implanted C6 glioma. Gd@Ful was shown to reduce proton relaxation times in vitro, and provide dual contrast of T1- and T2-weighted images in a rat brain tumour model after paramagnetic intravenous delivery. Magnetic relaxation times and relaxivity of water protons under action of Gd@Ful were strongly shortened due to cluster formation and increase of motional correlation times of protons in the vicinity of the fulleren cage. The Gd@Ful administration promoted the improvement of glioma contrast enhancement at T2-weighted images due to accumulation of paramagnetic substance at the tumour site. The contrast efficiency of Gd@Ful corresponds to the characteristics of negative contrast agent. Retention of the Gd@Ful in the C6 glioma provides not only the tumor contrast enhancement but also has a high therapeutic relevance. We observed the increased survival rates in animals that were intravenously administered with Gd@Ful. Thus, in experimental group the survival was 75% higher then in the control group, constituting 34.2 ± 9.94 and 19.5 ± 3.02 days respectively (P < 0.001). The Gd@Ful solution is shown to be a contrast enhancer with high anti-tumour therapeutic potency.
Detecting of the minimal residual disease contaminated in peripheral blood stem cell transplantation in the B‐Cell malignant lymphoma patients
Authors: Masaya Nagasu, Shin Aizawa, Hitoshi Hojo, Akemi Tsuda, Makoto Yaguchi, Masaru Nakano, Keisuke Toyama
Journal: American Journal of Hematology (1992)

Abstract For sufficient collection of hemopoietic stem cells from peripheral blood for autologous peripheral blood stem cell transplantation (PBSCT), four patients with B‐cell‐type non‐Hodgkin lymphoma (B‐NHL) were examined for the appearance of circulating hemopoietic progenitors in blood (PSC) during the hemopoietic recovery phase following marrow ablative therapy in combination with or without administration of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF). Each patient received only chemotherapy in the first course, and rhG‐CSF (1 βg/kg/day) was administered for 14 consecutive days from the last day of the second chemotherapy. In the second chemotherapy course with rhG‐CSF administration, white blood cell (WBC) counts demonstrated two peaks, and the appearance of granulocyte–macrophage precursor cells (CFU‐GM) in blood at the maximum level was coincident with the second peak of WBC elevation. Erythroid precursor cells (BFU‐E) were also detectable in blood after chemotherapy but the peak level was not enhanced by the use of rhG‐CSF. To determine whether the minimal residual disease (MRD) cells were contaminated in PSC corrected from blood, kappa–lambda imaging (KLI) analysis was performed to detect the malignant B‐cell population (mBp) before and after chemotherapy. No mBp was found in two of four patients in blood, although three of them were involved with mBp in bone marrow. The presence of mBp was detected in two patients both before and after chemotherapy, even though these cells were hardly detected morphologically, suggesting the necessity of judging for the incidence of contamination of MRD cells when collecting PSCs. © 1992 Wiley‐Liss, Inc.
Selective impairment of baroreflex-mediated vasoconstrictor responses in patients with ventricular dysfunction.
Authors: D W Ferguson, F M Abboud, A L Mark
Journal: Circulation (1984)

Cardiac dysfunction in animals has been associated with impairment of arterial and cardiopulmonary baroreflex control of the circulation. Chronic heart failure in human beings is associated with neurohumoral excitation, which could result in part from impairment in the inhibitory influence of baroreflexes. We postulated that (1) patients with left ventricular dysfunction (LVD) have impaired baroreflex modulation of vascular resistance and (2) administration of a digitalis glycoside would immediately restore baroreflex sensitivity. Eleven patients with LVD (NYHA class, 2.8 +/- 0.2, mean +/- SEM; baseline left ventricular ejection fraction, 18 +/- 2%; cardiac index, 2.4 +/- 0.21/min/m2; and pulmonary capillary wedge pressure, 26.0 +/- 3.2 mm Hg) were compared with 17 normal control subjects. We measured forearm vasoconstrictor responses to simulated orthostatic stress with use of lower body negative pressure (LBNP) at -10 and -40 mm Hg to unload cardiopulmonary and arterial baroreceptors. Baseline forearm vascular resistance (FVR) was higher in patients with LVD than in normal subjects: FVRLVD, 68.8 +/- 15.3 U; FVRN, 23.2 +/- 2.1 U (p less than .001). During unloading of baroreceptors with LBNP -10 mm Hg, normal subjects developed vasoconstriction (delta VRN at LBNP -10 mm Hg, +5.7 +/- 1.6 U) but patients with LVD failed to have vasoconstriction and tended to develop vasodilation (delta FVRLVD at LBNP -10 mm Hg, -8.6 +/- 8.5 U) (p = .05, normals vs patients with LVD at LBNP -10 mm Hg). A more marked disparity in response was seen during unloading of baroreceptors of LBNP -40 mm Hg: delta FVRN at LBNP -40 mm Hg, +16.6 +/- 1.5 U; delta FVRLVD at LBNP -40 mm Hg, -10.3 +/- 9.6 U (p less than .001, normals vs patients with LVD). Despite high baseline values for FVR, patients with LVD developed vasoconstriction during intra-arterial infusions of norepinephrine, thereby excluding a nonspecific depression of vascular reactivity as the mechanism for abnormal responses to LBNP in patients with LVD. We also studied the short-term effects of administration of a digitalis glycoside, ouabain 0.0075 mg/kg (seven patients) or lanatoside C (Cedilanid-D) 0.02 mg/kg (three patients), on baroreflex-mediated vasoconstrictor responses to LBNP in the patients with LVD. Digitalis glycoside reduced baseline FVR from 71.8 +/- 16.6 to 48.6 +/- 12.0 U (p less than .02). Responses to LBNP tended to be normalized after administration of digitalis glycoside: delta FVR during LBNP -40 mm Hg, -11.1 +/- 10.5 U before and +7.8 +/- 5.6 U after the drug (p less than .05).(ABSTRACT TRUNCATED AT 400 WORDS)
Further Applications of Scintillation Scanning Technics to the Diagnosis and Management of Infants and Children with Congenital Heart Disease
Authors: ARTHUR D. HAGAN, WILLIAM F. FRIEDMAN, WILLIAM L. ASHBURN, NAOMI ALAZRAKI
Journal: Circulation (1972)

Radionuclide angiography provides a reliable and extremely rapid technic for assessing the physiologic and pathologic features of cardiovascular malformations. Eighty-six infants and children and seven adults have been studied after intravenous infusion of 99m technetium with a scintillation camera coupled to a computer-tape storage system. Pulmonary vascular isotope-dilution curves detected the presence or absence of left-to-right intra- or extracardiac shunts with great sensitivity. Therefore, the method has especially widespread applicability in the distinction between organic and innocent heart murmurs, in the evaluation of postoperative patients, and in the assessment of the natural course of selected, specific malformations. Moreover, also without resorting to cardiac catheterization, scintillation scanning is capable of defining great artery orientation and position, cardiac chamber position, approximate chamber volumes, and the distribution of pulmonary arterial blood flow. The method described is technically simple, without known risk, is easily applicable to large numbers of patients, and provides clinically important information concerning many forms of congenital heart disease.
The Results of Surgical Treatment of Chronic Regional Enteritis
Authors: LeRoy H. Stahlgren
Journal: JAMA (1961)

Chronic regional enteritis recurred in 28 (53%) of 52 patients within five years after 86 definitive operations. Despite the high rate of recurrence, 42 (81%) of the patients were restored to satisfactory health. Certain conditions predisposed to recurrence. It was more frequent in patients under 30 years of age (62%) than in those over 40 (30%) and more frequent in patients with extensive disease (67%) than in those with localized disease (42%). All patients with extensive mesenteric lymphadenopathy suffered recurrences, and 69% of patients with a previous recurrence suffered further recurrence. Satisfactory rehabilitation was achieved in 62% of the patients with recurrent disease by combined medical and surgical therapy.
Immune Deficiency Syndrome in Children-Reply
Authors: James M. Oleske
Journal: JAMA (1983)

<h3>In Reply.—</h3> Rosner and Giron take issue with our suggestion that infants and children living in high-risk households may be in jeopardy of experiencing AIDS. They seem to believe in an<i>exclusively</i>perinatal or in utero mode of acquisition. We used household exposure in the broadest context to contrast with routine congenital immunodeficiency or infection and included a statement on so-called vertical transmission. Indeed, we have previously written on the latter possibility but believe that the monolithic position they take on pathogenesis is unwarranted.<sup>1</sup> We are aware of the data quoted on immunodeficiency in female sexual partners of men with AIDS. The mothers of the two infants in our report fathered by men with AIDS remain asymptomatic but have now experienced T-cell dysfunction themselves. Nevertheless, we are receptive to suggestions of other possible methods of spread. Analogies between the epidemiology of hepatitis B virus (HBV) and AIDS have been
Widespread expression of Huntington's disease gene (IT15) protein product
Authors: Alan H Sharp, Scott J Loev, Gabriele Schilling, Shi-Hua Li, Xiao-Jiang Li, Jun Bao, Molly V Wagster, Joyce A Kotzuk, Joseph P Steiner, Amy Lo, John Hedreen, Sangram Sisodia, Solomon H Snyder, Ted M Dawson, David K Ryugo, Christopher A Ross
Journal: Neuron (1995)

Huntington's Disease (HD) is caused by expansion of a CAG repeat within a putative open reading frame of a recently identified gene, IT15. We have examined the expression of the gene's protein product using antibodies developed against the N-terminus and an internal epitope. Both antisera recognize a 350 kDa protein, the predicted size, indicating that the CAG repeat is translated into polyglutamine. The HD protein product is widely expressed, most highly in neurons in the brain. There is no enrichment in the striatum, the site of greatest pathology in HD. Within neurons, the protein is diminished in nuclei and mitochondria and is present in the soluble cytoplasmic compartment, as well as loosely associated with membranes or cytoskeleton, in cell bodies, dendrites, and axons. It is concentrated in nerve terminals, including terminals within the caudate and putamen. Thus, the normal HD gene product may be involved in common intracellular functions, and possibly in regulation of nerve terminal function. The product of the expanded allele is expressed, consistent with a gain of function mechanism for HD at the protein level.
Deficiency in the Detection of Microalbuminuria by Urinary Dipstick in Diabetic Patients
Authors: Wayne D. Comper, Tanya M. Osicka
Journal: Diabetes Care (2004)

We would like to assure Selgren (1) that in 2002, the American Diabetes Association could find no published study that fulfilled their requirements of a detection rate of >95% for abnormal samples from patients with microalbuminuria for qualitative (or semiquantitiative) dipstick tests. This was quite independent of measuring albumin by the high-performance liquid chromatography (HPLC) method. We only noted that the American Diabetes Association came to the same conclusion as we …
Insulin Resistance and Hyperinsulinemia
Authors: Michael H. Shanik, Yuping Xu, Jan Škrha, Rachel Dankner, Yehiel Zick, Jesse Roth
Journal: Diabetes Care (2008)

Insulin resistance, recently recognized as a strong predictor of disease in adults, has become the leading element of the metabolic syndrome and renewed as a focus of research. The condition exists when insulin levels are higher than expected relative to the level of glucose. Thus, insulin resistance is by definition tethered to hyperinsulinemia. The rising prevalence of medical conditions where insulin resistance is common has energized research into the causes. Many causes and consequences have been identified, but the direct contributions of insulin itself in causing or sustaining insulin resistance have received little sustained attention. We examine situations where insulin itself appears to be a proximate and important quantitative contributor to insulin resistance. 1) Mice transfected with extra copies of the insulin gene produce basal and stimulated insulin levels that are two to four times elevated. The mice are of normal weight but show insulin resistance, hyperglycemia, and hypertriglyceridemia. 2) Somogyi described patients with unusually high doses of insulin and hyperglycemia. Episodes of hypoglycemia with release of glucose-raising hormones, postulated as the culprits in early studies, have largely been excluded by studies including continuous glucose monitoring. 3) Rats and humans treated with escalating doses of insulin show both hyperinsulinemia and insulin resistance. 4) The pulsatile administration of insulin (rather than continuous) results in reduced requirements for insulin. 5) Many patients with insulinoma who have elevated basal levels of insulin have reduced (but not absent) responsiveness to administered insulin. In summary, hyperinsulinemia is often both a result and a driver of insulin resistance.
Relation of bronchial responsiveness to body mass index in the ECRHS
Authors: S Chinn, D Jarvis, P Burney
Journal: Thorax (2002)

<b>Background:</b> There is substantial evidence for an association between symptoms of asthma and overweight or obesity. However, a study that reported no association between bronchial responsiveness (BHR) and body mass index (BMI) suggested that the relation of symptoms to obesity was due to increased diagnosis of asthma. The relation of BHR to BMI was therefore investigated in a large multicentre study. <b>Methods:</b> Data were obtained for 11 277 participants in stage II of the European Community Respiratory Health Survey (ECRHS). BHR to methacholine was analysed in relation to BMI adjusted for a number of factors known to be associated with BHR, including baseline lung function and allergen sensitisation, and combined across 34 centres using random effects meta-analysis. <b>Results:</b> BHR increased with increasing BMI in men (ECRHS slope changed by –0.027 for each unit increase in BMI, 95% confidence interval –0.044 to –0.010, p=0.002), but the relation in women was weak (–0.014, 95% CI –0.033 to 0.005, p=0.14). There was no evidence for an interaction of sex with BMI (p=0.41). <b>Conclusions:</b> BHR is related to BMI in the ECRHS. This suggests that the association is not due to greater diagnosis or perception of symptoms in obese people compared with those of normal weight. The data do not support the finding by some studies of a relation between asthma and obesity in women but not in men.
<i>N</i>‐trimethylchitosan/Alginate Layer‐by‐Layer Self Assembly Coatings Act as “Fungal Repellents” to Prevent Biofilm Formation on Healthcare Materials
Authors: Fuguang Jiang, Chih‐Ko Yeh, Jianchuan Wen, Yuyu Sun
Journal: Advanced Healthcare Materials (2014)

Fungal biofilm formation on healthcare materials is a significant clinical concern, often leading to medical-device-related infections, which are difficult to treat. A novel fungal repellent strategy is developed to control fungal biofilm formation. Methylacrylic acid (MAA) is grated onto poly methyl methacrylate (PMMA)-based biomaterials via plasma-initiated grafting polymerization. A cationic polymer, trimethylchitosan (TMC), is synthesized by reacting chitosan with methyl iodide. Sodium alginate (SA) is used as an anionic polymer. TMC/SA multilayers are coated onto the MAA-grafted PMMA via layer-by-layer self-assembly. The TMC/SA multilayer coatings significantly reduce fungal initial adhesion, and effectively prevent fungal biofilm formation. It is concluded that the anti-adhesive property of the surface is due to its hydrophilicity, and that the biofilm-inhibiting action is attributed to the antifungal activity of TMC as well as the chelating function of TMC and SA, which may have acted as fungal repellents. Phosphate buffered saline (PBS)-immersion tests show that the biofilm-modulating effect of the multilayer coatings is stable for more than 4 weeks. Furthermore, the presence of TMC/SA multilayer coatings improves the biocompatibility of the original PMMA, offering a simple, yet effective, strategy for controlling fungal biofilm formation.