tbuckley/cabot-search huggingface dataset:
Injectable Sustained Release Microparticles of Curcumin: A New Concept for Cancer Chemoprevention
Authors: Komal Shahani, Suresh Kumar Swaminathan, Diana Freeman, Angela Blum, Linan Ma, Jayanth Panyam
Journal: Cancer Research (2010)

Abstract Poor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and biocompatible polymer, poly(d,l-lactide-co-glycolide), was used to fabricate curcumin microparticles. When injected s.c. in mice, a single dose of microparticles sustained curcumin levels in the blood and other tissues for nearly a month. Curcumin levels in the lungs and brain, frequent sites of breast cancer metastases, were 10- to 30-fold higher than that in the blood. Further, curcumin microparticles showed marked anticancer efficacy in nude mice bearing MDA-MB-231 xenografts compared with other controls. Repeated systemic injections of curcumin were not effective in inhibiting tumor growth. Treatment with curcumin microparticles resulted in diminished vascular endothelial growth factor expression and poorly developed tumor microvessels, indicating a significant effect on tumor angiogenesis. These results suggest that sustained delivery of chemopreventives such as curcumin using polymeric microparticles is a promising new approach to cancer chemoprevention and therapy. Cancer Res; 70(11); 4443–52. ©2010 AACR.
Psychosocial Treatment for First-Episode Psychosis: A Research Update
Authors: David L Penn, Evan J Waldheter, Diana O Perkins, Kim T Mueser, Jeffrey A Lieberman
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This article reviews research on psychosocial treatment for first-episode psychosis. METHOD: PsycINFO and MEDLINE were systematically searched for studies that evaluated psychosocial interventions for first-episode psychosis. RESULTS: Comprehensive (i.e., multielement) treatment approaches show promise in reducing symptoms and hospital readmissions, as well as improving functional outcomes, although few rigorously controlled trials have been conducted. Individual cognitive behavior therapy has shown modest efficacy in reducing symptoms, assisting individuals in adjusting to their illness, and improving subjective quality of life, but it has shown minimal efficacy in reducing relapse. Some controlled research supports the benefits of family interventions, while less controlled research has evaluated group interventions. CONCLUSIONS: Adjunctive psychosocial interventions early in psychosis may be beneficial across a variety of domains and can assist with symptomatic and functional recovery. More randomized, controlled trials are needed to evaluate the effectiveness of these interventions, particularly for multielement, group, and family treatments.
A Phase III Trial of Fluoropyrimidines (FP) Plus Bevacizumab (BEV) vs. Bev Alone, or No Treatment as Maintenance Strategy, Following a Standard Combination of FP, Oxaliplatin (OX), and Bev as First-Line Treatment for Patients with Metastatic Colorectal Cancer (MCRC): AIO KRK 0207
Authors: D. Arnold, C. Lerchenmüller, B. Killing, R. Depenbusch, C.C. Steffens, S.E. Al-Batran, J. Quidde, T. Lange, G. Dietrich, J. Stoehlmacher, A. Reinacher-Schick, A. Tannapfel, T. Graeven, H.J. Schmoll, S. Hegewisch-Becker
Journal: Annals of Oncology (2014)
The Pharmacokinetics and Safety of ABT-751, a Novel, Orally Bioavailable Sulfonamide Antimitotic Agent: Results of a Phase 1 Study
Authors: Kenneth R. Hande, Anne Hagey, Jordan Berlin, Yingna Cai, Kysa Meek, Hiro Kobayashi, A. Craig Lockhart, Diane Medina, Jeffrey Sosman, Gary B. Gordon, Mace L. Rothenberg
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Microtubules play a critical role in many cellular functions, including cell division and mitosis. ABT-751 is a novel sulfonamide antimitotic that binds to the colchicine site on β-tubulin that leads to a block in the cell cycle at the G2M phase, resulting in cellular apoptosis. ABT-751 was investigated in this phase 1 trial designed to assess its maximum tolerated dose (MTD), dose-limiting toxicity (DLT), tolerability, and pharmacokinetics. Experimental Design: ABT-751 was administered on a daily (q.d.) or twice daily (b.i.d.) oral schedule for 7 days every 3 weeks to 39 patients with refractory solid tumors. Toxicity was monitored weekly. Plasma and urine ABT-751 and metabolite pharmacokinetics were determined. Results: The MTD for the q.d. schedule was 250 mg/d. DLTs during cycle 1 were abdominal pain, constipation, and fatigue. The MTD on the b.i.d. schedule was 150 mg. Cycle 1 of therapy with the 175 mg b.i.d. schedule was tolerated without DLT. However, six of seven patients reported grade 3 toxicity (ileus, constipation, abdominal pain, or fatigue), which occurred in cycle 2 or 3. ABT-751 was absorbed after oral administration with an overall mean Tmax of about 2 hours. The pharmacokinetics of ABT-751 were dose-proportional and time-independent. There was minimal accumulation of ABT-751 after multiple q.d. and b.i.d. doses. Efficacious concentrations, as determined from preclinical models (0.5-1.5 μg/mL), were achieved in all subjects. ABT-751 metabolism occurred primarily by glucuronidation and sulfation. No complete or partial tumor responses were noted, but one patient had a minor response, and four patients had stable disease lasting at least 6 months. Conclusions: The MTD and recommended phase 2 doses for ABT-751 were 250 mg q.d. and 150 mg b.i.d. on a 7-day schedule given every 3 weeks, due to subsequent cycle toxicities at 175 mg b.i.d. dosing. Toxicities were abdominal pain, constipation, and neuropathy.
Laboratory diagnosis of porphyria
Authors: S. R. Gambino
Journal: JAMA (1969)

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis.Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations.Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients.Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying presymptomatic carriers.The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria.This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.
Effects of different sodium concentrations in replacement fluids during prolonged exercise in women
Authors: R Twerenbold, B Knechtle, T H Kakebeeke, P Eser, G Müller, P von Arx, H Knecht
Journal: British Journal of Sports Medicine (2003)

To investigate the effect of different sodium concentrations in replacement fluids on haematological variables and endurance performance during prolonged exercise.Thirteen female endurance athletes completed three four hour runs on a 400 m track. Environmental conditions differed between the three trials: 5.3 degrees C and snow (trial 1), 19.0 degrees C and sunny weather (trial 2), 13.9 degrees C and precipitation (trial 3). They consumed 1 litre of fluid an hour during the trials with randomised intake of fluids: one trial (H) with high sodium concentration (680 mg/l), one trial (L) with low sodium concentration (410 mg/l), and one trial with only water (W). Before and after the trials, subjects were weighed and blood samples were taken for analysis of [Na(+)](plasma), packed cell volume, and mean corpuscular volume.The mean (SD) decrease in [Na(+)](plasma) over the whole trial was significantly (p<0.001) less in trial H (2.5 (2.5) mmol/l) than in trial W (6.2 (2.1) mmol/l). Mild hyponatraemia ([Na(+)](plasma) = 130-135 mmol/l) was observed in only six women (46%) in trial H compared with nine (69%) in trial L, and 12 (92%) in trial W. Two subjects (17%) in trial W developed severe hyponatraemia ([Na(+)](plasma)<130 mmol/l). No significant differences were found in performance or haematological variables with the three different fluids. There was no significant correlation between[Na(+)](plasma) after the run and performance. There was a significant correlation between changes in [Na(+)](plasma) and changes in body weight.Exercise induced hyponatraemia in women is likely to develop from fluid overload during prolonged exercise. This can be minimised by the use of replacement fluids of high sodium concentration. Sodium replacement of at least 680 mg/h is recommended for women in a state of fluid overload during endurance exercise of four hours. However, higher [Na(+)](plasma) after the run and smaller decreases in [Na(+)](plasma) during the trials were no indication of better performance over four hours.
Vascular Morphogenesis and Remodeling in a Model of Tissue Repair
Authors: Sybill Patan, Lance L. Munn, Shigeru Tanda, Sylvie Roberge, Rakesh K. Jain, Rosemary C. Jones
Journal: Circulation Research (2001)

To investigate mechanisms of vascular morphogenesis in tissue repair, we performed ovariectomy with resection of the corresponding branches of the ovarian vessels in nude mice. This induces a vascular network remodeling response in the healing ovarian pedicle. Reconstruction of 2000 histological serial sections demonstrated that a new vascular network composed of venous-venous loops forms in the wall of the dilated ovarian vein. Preexisting veins of all sizes, including a branch of the main artery, are subjected to segmentation. Loop formation and segmentation are based on intussusceptive microvascular growth. Loop formation is followed by elongation. Loop remodeling occurs also by intussusception and results in the formation of compound loop systems. All loop systems observed were completely patent. Blind-ending sprouts were extremely rare. Anastomoses between the preexisting vessels subjected to segmentation and the loop systems were established to include the newly formed vessels into the preexisting vascular network. The formation of an increasing number of patent loop systems likely decreases hypoxia and subsequently arrests angiogenesis with transformation of the granulation tissue into a scar. Loop formation also occurred inside a large thrombus that occluded a part of the lumen of the main vein.
Use of a Continuous-Flow Device in Patients Awaiting Heart Transplantation
Authors: Leslie W. Miller, Francis D. Pagani, Stuart D. Russell, Ranjit John, Andrew J. Boyle, Keith D. Aaronson, John V. Conte, Yoshifumi Naka, Donna Mancini, Reynolds M. Delgado, Thomas E. MacGillivray, David J. Farrar, O.H. Frazier
Journal: New England Journal of Medicine (2007)

The use of left ventricular assist devices is an accepted therapy for patients with refractory heart failure, but current pulsatile volume-displacement devices have limitations (including large pump size and limited long-term mechanical durability) that have reduced widespread adoption of this technology. Continuous-flow pumps are newer types of left ventricular assist devices developed to overcome some of these limitations.In a prospective, multicenter study without a concurrent control group, 133 patients with end-stage heart failure who were on a waiting list for heart transplantation underwent implantation of a continuous-flow pump. The principal outcomes were the proportions of patients who, at 180 days, had undergone transplantation, had cardiac recovery, or had ongoing mechanical support while remaining eligible for transplantation. We also assessed functional status and quality of life.The principal outcomes occurred in 100 patients (75%). The median duration of support was 126 days (range, 1 to 600). The survival rate during support was 75% at 6 months and 68% at 12 months. At 3 months, therapy was associated with significant improvement in functional status (according to the New York Heart Association class and results of a 6-minute walk test) and in quality of life (according to the Minnesota Living with Heart Failure and Kansas City Cardiomyopathy questionnaires). Major adverse events included postoperative bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in two patients.A continuous-flow left ventricular assist device can provide effective hemodynamic support for a period of at least 6 months in patients awaiting heart transplantation, with improved functional status and quality of life. (ClinicalTrials.gov number, NCT00121472 [ClinicalTrials.gov].).
THE BACTERIOSTATIC ACTION OF CERTAIN COMPONENTS OF COMMERCIAL PEPTONES AS AFFECTED BY CONDITIONS OF OXIDATION AND REDUCTION
Authors: René Dubos
Journal: The Journal of Experimental Medicine (1930)

There are present in commercial peptones substances which exhibit bacteriostatic properties for certain bacterial species. These substances are bacteriostatic in the oxidized form, but not in the reduced form. Their bacteriostatic action can be overcome, and their concentration titrated, by the addition of reduced thiol compounds to the media in which they are present. Different brands of peptone differ greatly in the amount of bacteriostatic substances they contain; these differences account, in part at least, for the fact that media prepared from the same meat infusion, but with different kinds of peptone, vary in their ability to support bacterial growth. The bacteriostatic fraction of a certain peptone solution can be completely removed by precipitation with acid and acetone. A peptone which has thus been purified becomes capable of supporting the growth of very small inocula of Pneumococcus. The significance of the sensitiveness of certain bacterial species to substances which are bacteriostatic in the oxidized but not in the reduced form is considered with reference to (a) the mechanism of bacteriostasis, (b) the growth of bacterial species in artificial media, (c) the problem of infection.
Reforming the Cancer Drug Fund
Authors: M. Buxton, L. Longworth, J. Raftery, M. Sculpher, A. Towse
Journal: BMJ (2014)

Focus on drugs that might be shown to be cost effective

The Cancer Drug Fund was originally conceived as a temporary measure, until value based pricing for drugs was introduced, to give NHS cancer patients access to drugs not approved by NICE. Spending on these drugs rose from less than the £50m (€63m; $79m) budgeted for the first year in 2010-11 to well over £200m in 2013-14, and the budget for the scheme—now extended for a further two years—will reach £280m by 2016.1 The recent changes to the fund recognise the impossibility, within any sensible budget limit, of providing all the new cancer drugs that offer possible benefit to patients. More radical changes are needed to the working of the fund, given the failure to introduce value based pricing, so that it deals with the underlying problem of inadequate information on the effectiveness and cost effectiveness of new cancer drugs when used in the NHS.

A recent The BMJ briefing identified major problems with the fund.2 The opportunity costs in terms of the treatments that cannot, as a result, be afforded elsewhere in the NHS are substantial, with consequent decrements to other patients’ health. Its operation undermines the role of the National Institute for Health and Care Excellence (NICE). A rejection from NICE on the grounds that a drug is not cost effective (at the price proposed …
Utilizing the adjuvant properties of CD1d-dependent NK T cells in T cell–mediated immunotherapy
Authors: Jonathan D. Silk, Ian F. Hermans, Uzi Gileadi, Tsung Wen Chong, Dawn Shepherd, Mariolina Salio, Bini Mathew, Richard R. Schmidt, Sarah Jane Lunt, Kaye J. Williams, Ian J. Stratford, Adrian L. Harris, Vincenzo Cerundolo
Journal: Journal of Clinical Investigation (2004)

Activation of invariant CD1d-dependent NK T cells (iNKT cells) in vivo through administration of the glycolipid ligand α-galactosylceramide (α-GalCer) or the sphingosine-truncated α-GalCer analog OCH leads to CD40 signaling as well as the release of soluble molecules including type 1 and γ interferons that contribute to DC maturation. This process enhances T cell immunity to antigens presented by the DC. The adjuvant activity is further amplified if APCs are stimulated through Toll-like receptor 4, suggesting that iNKT cell signals can amplify maturation induced by microbial stimuli. The adjuvant activity of α-GalCer enhances both priming and boosting of CD8+ T cells to coadministered peptide or protein antigens, including a peptide encoding the clinically relevant, HLA-A2–restricted epitope of the human tumor antigen NY-ESO-1. Importantly, α-GalCer was used to induce CD8+ T cells to antigens delivered orally, despite the fact that this route of administration is normally associated with blunted responses. Only T cell responses induced in the presence of iNKT cell stimulation, whether by the i.v. or oral route, were capable of eradicating established tumors. Together these data highlight the therapeutic potential of iNKT cell ligands in vaccination strategies, particularly "heterologous prime-boost" strategies against tumors, and provide evidence that iNKT cell stimulation may be exploited in the development of oral vaccines.
An indolent penile herpetic ulcer in a patient with previously undiagnosed human immunodeficiency virus infection
Authors: None Tayal, None Pattman, None Mclelland, None Sviland, None Snow
Journal: British Journal of Dermatology (1998)

We report a case of an atypical penile herpetic ulcer in a man with previously undiagnosed human immunodeficiency virus (HIV) infection. Swabs of the lesion were negative for herpes simplex virus (HSV) by culture and electron microscopy. However, histopathology of biopsy material showed characteristic herpetic multinucleate giant cells. Immunochemistry using polyclonal antibodies was positive for HSV1 and HSV2. The lesion completely resolved after treatment with aciclovir and the patient subsequently tested positively for HIV antibodies.
The College Student in the Psychiatric Clinic: Syndromes and Subcultural Sanctions
Authors: JAMES L. EVANS
Journal: American Journal of Psychiatry (1970)

In presenting his observations about college students who seek psychiatric help, the author offers some suggestions for a clinical and psychodynamic approach that takes into consideration the current subcultural group characteristics of college students. Also described are the ways in which the student's environment affects his adaptation and the ways in which the environment may in turn be used by the student in maintaining various drive-defense combinations.
Circulating 25-hydroxyvitamin D is associated with insulin resistance cross-sectionally but not longitudinally in older adults: The Cardiovascular Health Study
Authors: John Danziger, Mary L. Biggs, Matt Niemi, Joachim H. Ix, Jorge R. Kizer, Luc Djoussé, Ian H. de Boer, David S. Siscovick, Bryan Kestenbaum, Kenneth J. Mukamal
Journal: Metabolism (2013)
DNA bend sites in the human beta-globin locus: evidence for a basic and universal structural component of genomic DNA
Authors: Y. Wada-Kiyama, K. Suzuki, R. Kiyama
Journal: Molecular Biology and Evolution (1999)

Here we summarize the DNA bend sites in a 66-kb region of the human beta-globin locus. A total of 98 sites were mapped by circular permutation assay along the locus with an average interval of 679.2 +/- 229.6 bp between them. The distribution of the bend sites indicated that although the most frequent distance was about 650-700 bp, there appeared to be preferences at 300-400, 500-550, 800-850, 1,000-1,050, and 1,150-1,200 bp, indicating that these distances are multimers of a 170-bp basic unit. DNA bend sites in the globin-encoding regions indicated that most of their locations relative to the cap sites were conserved during evolution. Insertion of Alu and L1 sequences that occurred at various times and changed the distances of the sites was corrected for the epsilon-, psi beta-, and delta-globin genes. The only exception of the conservation was observed at the duplication junctions of the two gamma-globin genes, which occurred 25-35 MYA. Among the 75 A/A/A (A2N8A2N8A2) sequences found in the 51 bend sites, 59 sequences from 47 sites showed bending profiles by oligonucleotide-based assay. All of these sites were included in the sites predicted by computer analysis based on the distribution of AA and TT dinucleotides. These lines of evidence suggest that these DNA bend sites are one of the basic structural components universally present in genomic DNA.
Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation Reduced-Dose Whole-Brain Radiotherapy and Cytarabine in Newly Diagnosed Primary CNS Lymphoma: Final Results and Long-Term Outcome
Authors: Patrick G. Morris, Denise D. Correa, Joachim Yahalom, Jeffrey J. Raizer, David Schiff, Barbara Grant, Sean Grimm, Rose K. Lai, Anne S. Reiner, Kathy Panageas, Sasan Karimi, Richard Curry, Gaurav Shah, Lauren E. Abrey, Lisa M. DeAngelis, Antonio Omuro
Journal: Journal of Clinical Oncology (2013)

A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma.Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor.Fifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R-MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was 7.7 years. Median overall survival (OS) was not reached (median follow-up for survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3 years, and median OS was 6.6 years. Cognitive assessment showed improvement in executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and follow-up scores remained relatively stable across the various domains (n = 12). All examined MRIs (n = 28) displayed a Fazekas score of ≤ 3, and no patient developed scores of 4 to 5; differences in ADC values did not predict response (P = .15), PFS (P = .27), or OS (P = .33).R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity.