tbuckley/cabot-search huggingface dataset:
Safety and Efficacy of Patupilone in Patients With Advanced Ovarian, Primary Fallopian, or Primary Peritoneal Cancer: A Phase I, Open-Label, Dose-Escalation Study
Authors: Wim W. ten Bokkel Huinink, Jozef Sufliarsky, Willem M. Smit, Stanislav Spanik, Maria Wagnerova, Hal W. Hirte, Stan Kaye, Anandhi R. Johri, Amit M. Oza
Journal: Journal of Clinical Oncology (2009)

PURPOSE To evaluate the safety, maximum tolerated dose (MTD), and pharmacokinetics of patupilone administered once every 3 weeks with proactive standardized diarrhea management in patients with resistant or refractory ovarian, fallopian, or peritoneal cancer. PATIENTS AND METHODS Patients received patupilone (6.5 to 11.0 mg/m(2)) every 3 weeks via 20-minute infusion. Adverse events, dose-limiting toxicities (DLT), MTD, and tumor response were determined. The tumor response was measured by Response Evaluation Criteria in Solid Tumors (RECIST) and cancer antigen 125 levels. Results Forty-five patients were enrolled. Adverse events were mild to moderate in intensity, and grade 3 diarrhea (13%) was the most commonly reported serious adverse event. Grade 3 peripheral neuropathy was noted in two patients (4%). Diarrhea, peripheral neuropathy, and fatigue were the most common DLTs; however, these were uncommon in the first cycle and the MTD was therefore not reached in this study. Overall response (OR; complete and partial responses; median cycles, 8) per RECIST in patients with measurable disease (n = 36) was 19.5%. Median duration of disease stabilization (complete and partial responses and stable disease) was 15.8 months. These results appear improved from a previous study in a similar patient population using a weekly schedule (2.5 mg/m(2)/week; N = 53; OR, 5.7%). CONCLUSION Patupilone once every 3 weeks was well-tolerated at doses up to 11.0 mg/m(2). Patupilone demonstrated promising antitumor activity in patients with drug-resistant/refractory disease. An ongoing phase III study in this patient population is testing the 10.0 mg/m(2) dose.
Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies
Authors: D. J. Palmer, T. Sullivan, M. S. Gold, S. L. Prescott, R. Heddle, R. A. Gibson, M. Makrides
Journal: Allergy (2013)

Background Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE-mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated allergic disease in their children. Methods Follow-up of children (n = 706) at hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomized controlled trial. The intervention group (n = 368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338) received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. Results No differences were seen in the overall percentage of children with IgE-mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78; 95% CI 0.58–1.06; P = 0.11). Eczema was the most common allergic disease; 13.8% of children in the n-3 LCPUFA group had eczema with sensitization compared with 19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53–1.05; P = 0.10). Conclusions Overall, n-3 LCPUFA supplementation during pregnancy did not significantly reduce IgE-associated allergic disease in the first 3 years of life. Further studies should examine whether the nonsignificant reductions in IgE-associated allergies are of clinical and public health significance.
Docosahexaenoic Acid Ameliorates Murine Ischemic Acute Renal Failure and Prevents Increases in mRNA Abundance for both TNF-α and Inducible Nitric Oxide Synthase
Authors: Mariusz L. Kielar, D. Rohan Jeyarajah, X. J. Zhou, Christopher Y. Lu
Journal: Journal of the American Society of Nephrology (2003)

This study demonstrates that intraperitoneal injections of DHA (all cis 4,7,10,13,16,19 docosahexaenoic acid C22: n-3) bound to bovine serum albumin ameliorate murine acute renal failure (ARF) induced by temporary occlusion of the renal artery. Three micromoles of DHA decreased serum creatinine (Scr) from 2.3 mg/dl to 1.1 mg/dl 24 h after reperfusion (n = 15; P < 0.05). Scr of the treated animals were significantly lower than controls throughout a 7-d time course. Although lower doses of DHA were less effective, higher doses were not more effective. Ribonuclease (RNase) protection assays showed that ischemia increased mRNA abundance for TNF-alpha and inducible nitric oxide synthase (iNOS) at 24 h. This increase was prevented by DHA administration. Because TNF-alpha and iNOS contribute to renal ischemic injury, their inhibition may contribute to DHA's salutary effect. In addition, the data may have therapeutic implications, because the DHA improves ARF even when administered at 4 h after reperfusion.
THE EFFECT OF WETTING AGENTS ON THE GROWTH OF TUBERCLE BACILLI
Authors: René J. Dubos, Gardner Middlebrook
Journal: The Journal of Experimental Medicine (1948)

Tween 80 and Triton A20 are two water-dispersible, non-ionic, surface-active agents which favor dispersed growth of tubercle bacilli in aqueous media probably by wetting the bacterial surface. Tween 80 is a polyoxyethylene ester of sorbitan monooleate and is liable to enzymatic hydrolysis by lipases. Triton A20 in an arylalkyl polyether of phenol which appears resistant to the known enzymes of animal tissues. Tween 80 loses its ability to disperse cultures of tubercle bacilli in media containing serum; Triton A20 does not. Tween 80 increases the yield of growth, probably by supplying oleic acid to the bacilli; Triton A20 does not. In concentrations sufficient to cause dispersed browth, Tween 80 (purified by removal of unesterified fatty acid) and Triton A20 are completely innocuous for virulent tubercle bacilli. However, Triton A20 exhibits a marked toxic effect on the avirulent variants of mammalian strains; Tween 80 does not. The two wetting agents also differ in their effects on the morphological aspects of the bacterial cultures. Whereas Triton A20 prevents the formation of large amorphous bacillary clumps, it is less effective in preventing the orientation of the virulent bacilli resulting in the formation of long bacillary strands. Tween 80 on the contrary prevents also the formation of these cords of bacilli and exerts therefore a more effective dispersing effect on cultures of virulent tubercle bacilli.
Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies
Authors: M Abu-Shakra, D Buskila, M Ehrenfeld, K Conrad, Y Shoenfeld
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVES</h3> To review the autoimmune and rheumatic manifestations of patients with malignancy. <h3>METHODS</h3> A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes. <h3>RESULTS</h3> Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (<i>a</i>) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). (<i>b</i>) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. (<i>c</i>) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy. <h3>CONCLUSION</h3> Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.
Prolonged Methylprednisolone Treatment Suppresses Systemic Inflammation in Patients with Unresolving Acute Respiratory Distress Syndrome
Authors: G. Umberto Meduri, Elizabeth A. Tolley, George P. Chrousos, Frankie Stentz
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Nuclear factor- κ B (NF- κ B) and glucocorticoid receptor- α (GR- α ) have diametrically opposed functions in regulating inflammation. We investigated whether unresolving acute respiratory distress syndrome (ARDS) is associated with systemic inflammation- induced glucocorticoid resistance and whether prolonged methylprednisolone administration accelerates the suppression of systemic inflammatory indices and normalizes the sensitivity of the immune system to glucocorticoids. Patients enrolled into a randomized trial evaluating prolonged methylprednisolone administration in unresolving ARDS had serial plasma samples collected before and after randomization. In the plasma, we measured the concentrations of tumor necrosis factor- α (TNF- α ), interleukins (IL) IL-1 β and IL-6, adrenocorticotropic hormone (ACTH), and cortisol. The ability of patient plasma to influence the NF- κ B and GR-signal transduction systems of normal peripheral blood leukocytes (PBL) was examined. Patients treated with methylprednisolone had progressive and sustained reductions of TNF- α , IL-1 β , IL-6, ACTH, and cortisol concentrations over time. Normal PBL exposed to plasma samples collected during methylprednisolone exhibited significant progressive increases in all aspects of GR-mediated activity and significant reductions in NF- κ B DNA-binding and transcription of TNF- α and IL-1 β . These findings provide support for the presence of endogenous glucocorticoid inadequacy in the control of inflammation and systemic inflammation-induced peripheral glucocorticoid resistance in ARDS. Prolonged methylprednisolone administration accelerated the resolution of both systemic inflammation and peripheral acquired glucocorticoid resistance in ARDS.
A hydroxyl radical–like species oxidizes cynomolgus monkey artery wall proteins in early diabetic vascular disease
Authors: Subramaniam Pennathur, Janice D. Wagner, Christiaan Leeuwenburgh, Kenneth N. Litwak, Jay W. Heinecke
Journal: Journal of Clinical Investigation (2001)

Recent evidence argues strongly that the marked increase in risk for atherosclerotic heart disease seen in diabetics cannot be explained by a generalized increase in oxidative stress. Here, we used streptozotocin to induce hyperglycemia in cynomolgus monkeys for 6 months and tested whether high glucose levels promote localized oxidative damage to artery wall proteins. We focused on three potential agents of oxidative damage: hydroxyl radical, tyrosyl radical, and reactive nitrogen species. To determine which pathways operate in vivo, we quantified four stable end products of these reactants — ortho-tyrosine, meta-tyrosine, o,o'-dityrosine, and 3-nitrotyrosine — in aortic proteins. Levels of ortho-tyrosine, meta-tyrosine, and o,o'-dityrosine, but not of 3-nitrotyrosine, were significantly higher in aortic tissue of hyperglycemic animals. Of the oxidative agents we tested, only hydroxyl radical mimicked this pattern of oxidized amino acids. Moreover, tissue levels of ortho-tyrosine and meta-tyrosine correlated strongly with serum levels of glycated hemoglobin, a measure of glycemic control. We conclude that short-term hyperglycemia in primates promotes oxidation of artery wall proteins by a species that resembles hydroxyl radical. Our observations suggest that glycoxidation reactions in the arterial microenvironment contribute to early diabetic vascular disease, raising the possibility that antioxidant therapies might interrupt this process.
Graded Activity for Low Back Pain in Occupational Health Care
Authors: J. Bart Staal, Hynek Hlobil, Jos W.R. Twisk, Tjabe Smid, Albère J.A. Köke, Willem van Mechelen
Journal: Annals of Internal Medicine (2004)

Background: Low back pain is a common medical and social problem frequently associated with disability and absence from work. However, data on effective return to work after interventions for low back pain are scarce. Objective: To determine the effectiveness of a behavior-oriented graded activity program compared with usual care. Design: Randomized, controlled trial. Setting: Occupational health services department of an airline company in the Netherlands. Patients: 134 workers who were absent from work because of low back pain were randomly assigned to either graded activity (n = 67) or usual care (n = 67). Intervention: Graded activity, a physical exercise program based on operant-conditioning behavioral principles, to stimulate a rapid return to work. Measurements: Outcomes were the number of days of absence from work because of low back pain, functional status (Roland Disability Questionnaire), and severity of pain (11-point numerical scale). Results: The median number of days of absence from work over 6 months of follow-up was 58 days in the graded activity group and 87 days in the usual care group. From randomization onward, graded activity was effective after 50 days of absence from work (hazard ratio, 1.9 [95% CI, 1.2 to 3.2]; P = 0.009). The graded activity group was more effective in improving functional status and pain than the usual care group. The effects, however, were small and not statistically significant. Conclusions: Graded activity was more effective than usual care in reducing the number of days of absence from work because of low back pain.
Directed neutrophil migration to IL-8 is increased in cystic fibrosis: a study of the effect of erythromycin
Authors: S Brennan
Journal: Thorax (2001)

<h3>BACKGROUND</h3> The aim of this study was to compare neutrophil migration in cystic fibrosis (CF) and non-CF populations and to investigate the effect of erythromycin on directed migration of neutrophils (PMNs) in CF. <h3>METHODS</h3> PMNs were isolated and their migratory capacity in response to interleukin-8 (IL-8) or f-Met-Leu-Phe (fMLP) in the presence or absence of erythromycin (1–100 μg/ml) was assessed. <h3>RESULTS</h3> CF derived PMNs showed significantly increased migration to IL-8 but not to fMLP compared with non-CF PMNs. Erythromycin had no significant effect on migration responses to IL-8 and in vitro exposure of PMNs to erythromycin had no effect. <h3>CONCLUSIONS</h3> CF derived PMNs show higher migratory responsiveness to IL-8 but not to fMLP, suggesting that CF PMNs may be "primed" to IL-8 which is significantly increased in CF serum compared with non-CF serum. Treatment with erythromycin had no significant effect on PMN migration in vitro.
Effects of intrapleural heparin or urokinase on the extent of tetracycline-induced pleural disease.
Authors: C Strange, M H Baumann, S A Sahn, S Idell
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Extravascular fibrin deposition is common at sites of pleural injury and has been related to loculation of pleural fluids. Although thrombolytic therapy has been used to treat pleural loculations, it has not been compared with pleural administration of anticoagulant therapy. We therefore tested interventional strategies designed to compare the relative effects of in vivo anticoagulation or supplemented fibrinolysis on pleural injury, and to characterize the local tissue responses to these modalities. Early intrapleural instillation of saline (Group 1), heparin 1,000 IU (Group 2), or urokinase (uPA) 1,500 IU (Group 3) every 12 h for 3 d was used to interrupt pleural adhesion formation and pleural fibrosis induced by tetracycline hydrochloride in rabbits. Procoagulant and fibrinolytic activities were determined in pleural effusion samples obtained serially every 12 h after the last administered intrapleural dose. Pleural fluid procoagulant activity was blocked by intrapleural heparin (p < 0.001), but plasminogen-dependent fibrinolytic activity was rarely increased by intrapleural urokinase. Most plasminogen activator activity in the pleural fluids was found at high-molecular-weight regions by enzymography, suggesting that it was bound to inhibitor(s). Pathologic analysis at 14 d demonstrated that the number of pleural adhesions in the heparin (8.4 +/- 3.4, mean +/- standard error) and uPA groups (6.1 +/- 2.5) was less than in saline-treated tetracycline controls (20.7 +/- 4.7) (both p < 0.02). Visceral pleural thickness did not differ between groups (p = NS). We conclude that intrapleural heparin or uPA are equally effective in decreasing intrapleural adhesions in tetracycline-induced pleural injury. The data indicate that early anticoagulation or fibrinolytic intervention can attenuate subsequent pleural symphysis in this model.
Aspirin-sensitive rhinitis-associated changes in upper airway innervation
Authors: D.A. Groneberg, W. Heppt, P. Welker, C. Peiser, Q. Thai Dinh, A. Cryer, M. Zweng, C. Witt, A. Fischer
Journal: European Respiratory Journal (2003)

Aspirin-sensitive rhinitis is the manifestation of aspirin intolerance in the upper respiratory tract. The disease represents a pseudoallergy against aspirin or related nonsteroidal anti-inflammatory drugs. As a major immunomodulatory role for airway innervation has been proposed in airway inflammatory diseases, the present study assessed changes in human nasal mucosa innervation in patients with aspirin-sensitive rhinitis in comparison to a control group. Immunohistochemistry for protein gene product 9.5, tachykinins, calcitonin gene-related peptide, vasoactive intestinal peptide (VIP) and neuropeptide tyrosine was performed on cryostats sections of nasal mucosa and neuropeptide containing nerves were examined independently using a score grading. In comparison to the control, the aspirin-sensitive rhinitis group had a significant increase of VIP‐like immunoreactivity in mucosal nerve fibres. In contrast to constant numbers of mast cells, highly significant increases in the numbers of eosinophils were found in the group of aspirin-sensitive rhinitis patients. In summary, the present quantification of neuropeptide-immunoreactivity of mucosal nerves demonstrated differences in the human nasal mucosa innervation between nonrhinitic and aspirin-sensitive rhinitic individuals. These differences may reflect a pathophysiological role of upper airway innervation in pseudoallergic reactions.
Immunosuppressive activity of a subline of the mouse EL-4 lymphoma. Evidence for minute virus of mice causing the inhibition.
Authors: G D Bonnard, E K Manders, D A Campbell, R B Herberman, M J Collins
Journal: The Journal of Experimental Medicine (1976)

Filtered culture fluids from the early in vitro passages of a subline of the C57BL/6 mouse EL-4 lymphoma, EL-4(G-), were strongly inhibitory for BABL/c vs. C57BL/6 mixed lymphocyte cultures (MLC). The inhibitory activity could be preserved by storage at -75 degrees C or 4 degrees C, thus allowing its further characterization. The inhibitory factor was particulate (nondialyzable, sedimentable at 100,000 g for 1 h), very small (recovered after 0.10 mum filtration), sensitive to UV irradiation, but heat stable (56 degrees C, 1 h) and resistant to chloroform. It was infectious, since later, noninhibitory passages of EL-4(G-) tissue culture cells became strongly inhibitory upon inoculation with the culture fluid. This data was consistent with the inhibitory factor being an infectious virus. Virus analysis by mouse antibody production tests revealed that viruses were indeed present in EL-4(G-) ascites cells and in the culture fluid, and not in a late passage of EL-4(G-) tissue culture cells which were not inhibitory. Neutralization of the inhibitory factor was achieved by pretreatment with ascitic fluid or with the sera raised against those (EL-4(G-)-derived materials which contained viruses. Mouse reference immune sera against minute virus of mice (MVM) completely neutralized the inhibitory factor in the culture fluid or in EL-4(G-) ascites cells. Two prototype MVM strains, and one Kilham rat virus preparation, did not inhibit the mouse MLC. Thus, the possibility exists that a variant of MVM, or an unidentified virus, has been grown and selected for in EL-4(G-) cells and recognized, due to its immunosuppressive characteristics. In any event, immunosuppression by EL-4(G-) cells was not mediated by the tumor cells, their metabolic products, or associated endogenous type C viruses, but by an exogenous virus, most likely a variant MVM with immunosuppressive characteristics. This adds weight to a parallel observation from our laboratory on the immunosuppressive effects of Kilham rat virus in rat lymphocyte cultures.
Qualitative Research: Introducing focus groups
Authors: J. Kitzinger
Journal: BMJ (1995)

This paper introduces focus group methodology, gives advice on group composition, running the groups, and analysing the results. Focus groups have advantages for researchers in the field of health and medicine: they do not discriminate against people who cannot read or write and they can encourage participation from people reluctant to be interviewed on their own or who feel they have nothing to say.
Targeted multi-epitope therapeutic vaccine for the treatment of invasive glioblastoma multiforme
Authors: Xiaofang Huang, Rashida Ginwala, Aykan Karabudak, Pooja Jain, Ramila Philip
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Invasive glioblastoma multiforme (GBM) is the most common malignant primary tumor of the central nervous system with an estimated annual incidence of 3.15 cases per 100,000 in the USA. Current therapies have been unsuccessful in curing malignant gliomas that are highly