tbuckley/cabot-search huggingface dataset:
P01.15 * ASSESSMENT OF A NOVEL MODIFIED KYTOZYME NANOPARTICLE TO CROSS AN 'ALL HUMAN' BLOOD BRAIN BARRIER MODEL
Authors: Z. Maherally, R. Philpott, E. Barbu, H. L. Fillmore, G. J. Pilkington
Journal: Neuro-Oncology (2014)

The blood brain barrier (BBB) consists mainly of endothelial cells, astrocytes and pericytes embedded in a specialized basement membrane. To properly evaluate the ability of novel brain tumour therapeutics to cross the BBB, an ‘all human’ model that better reflects in vivo conditions, critical for the BBB function and integrity has been developed to assess the delivery of modified Kytozyme nanoparticles (NPs). Human brain endothelial cells (hCMEC/D3), human cortical astrocytes (SC-1800) and human brain vascular pericytes (HBVP) in mono-, co- and tri- cultures were plated and TEER values were measured using an Electric Cell-Substrate Impedance Sensing (ECIS) system. Tight junction protein levels (ZO-1, occludin and β-catenin) were examined by Western blotting and immunocytochemistry. Response of culture combinations post NPs addition was assessed using cytotoxicity assay. Barrier integrity post-injection of NPs loaded in Evans Blue was monitored using live cell imaging. Co-cultures and tri-cultures resulted in significantly higher TEER values compared to endothelial cells alone (p < 0.05). Maximal TEER values for each condition were observed at 120 hours post plating. TEER values for co-culture (E + A) were 1250 Ω/cm2, and for tri-culture (E + A + P), 1190 Ω/cm2 compared to monoculture (E) (950 Ω/cm2). These peak values lasted for an additional 125 hours and provided plenty of time to test NP delivery. Western blot analysis revealed that ZO-1, occludin and β-catenin protein expression was higher in co- and tri-cultures compared to mono culture. In addition, ICC studies revealed localised expression of these tight junction proteins at cell-cell contacts whereas in monoculture, diffuse staining was observed. Following addition of Kytozyme NPs to the co-culture (E + A), at 120 hours, there was a decrease in TEER values (1250 Ω/cm2 to 1120 Ω/cm2) with a full recovery to peak TEER values within 12 hours suggesting passage through this BBB model. The addition of Evans Blue had no effect on TEER values. This study not only confirms that astrocytes contribute to BBB formation in terms of higher TEER values and in higher expression of ZO-1, occludin, and β-catenin proteins which are involved in tight junction formation but also provides an effective model with which to study nanoparticle drug delivery. We are now loading NPs with drugs to provide meaningful data that should help bridge the gap between drug discovery and pre-clinical studies.
FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial
Authors: Volker Heinemann, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christian Lerchenmüller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Jörg Hielscher, Michael Scholz, Sebastian Müller, Hartmut Link, Norbert Niederle, Andreas Rost, Heinz-Gert Höffkes, Markus Moehler, Reinhard U Lindig, Dominik P Modest, Lisa Rossius, Thomas Kirchner, Andreas Jung, Sebastian Stintzing
Journal: The Lancet Oncology (2014)
Change in Patients' Motivation for Psychotherapy
Authors: PETER E. SIFNEOS
Journal: American Journal of Psychiatry (1971)

In dynamic psychotherapy diagnostic and prognostic criteria are necessary in order to determine the kind of therapy best suited to a patient's idiosyncratic needs. Linked with these needs, and thus one important criterion, is a patient's motivation for change rather than for relief of symptoms. In order to assess this motivation, the author used a seven-point scale. Of 42 patients evaluated over eight treatment sessions, only nine patients' motivation for change decreased.
Enhancement of sickle erythrocyte adherence to endothelium by autologous platelets
Authors: Richard Antonucci, Richard Walker, John Herion, Eugene Orringer
Journal: American Journal of Hematology (1990)

Abstract The increased adhesiveness of sickle erythrocytes (SS RBC) to endothelial cells has been confirmed in a static system utilizing fresh umbilical vein endothelium. Adherence of SS RBC to the endothelium was as great in the presence of calcium‐containing buffer as when incubated in plasma. SS RBC suspended in autologous platelet‐rich plasma adhered to a greater extent than when suspended in autologous platelet poor plasma. Prostacyclin, thromboxane B 2 , and an inhibitor of collagen‐ and epinephrine‐induced platelet aggregation (B13.177) did not affect SS RBC adherence to endothelium. Aspirin in concentration of 5 μg/ml slightly decreased SS RBC adherence to endothelium in the presence of platelats may play a significant role in the increased adhesiveness of SS RBC to endothelium. To the extent that increasede SS RBC adhesiveness contributes to the genesis of painful crises and to the extent platelets augment this adhesiveness, agents affecting platelet function may prove useful in preventing painful crises.
Prognosis after myocardial infarction.
Authors: W Casscells
Journal: BMJ (1980)

dependent of the area of liposclerosis at the beginning of treatment.With leg ulcers there is some evidence' that healing follows a logarithmic curve, large ulcers healing faster than small ones.This biological phenomenon may well apply to the healing of liposclerosis; if so transformation-of the data is essential before paired comparisons are made.In the discussion the authors mention that other methods of assessing healing, such as percentage change, appeared to offer no advantages, but in what respect ?
Student Health and the B.M.S.A
Authors: J. A. Fletcher
Journal: BMJ (1947)

It seems obvious, therefore, that if these suggestions were acted on semi-permanent banishment of the child from its home environment would be necessitated, and I cannot feel that this disruption of family life would be approved of either on humanitarian grounds or by child psychiatrists even if prac- ticable, I was glad to read in your leading article that tuberculin-negative nurses certainly need protection, a point I erndeavoured to make in your correspondence columns some three years ago.Unfortunately, some -of our leading tuberculosis workers still await conversion to this belief.-Iam, etc.,
Voluntary Urine Testing of Physicians
Authors: Michael J. Scotti
Journal: JAMA (1987)

A NUMBER of suggestions have been made recently that American physicians can support the nationwide drive against drug abuse by voluntarily submitting to urine testing to show that they are drug free. As a career medical officer in the US Army, I have watched our mandatory screening program for a number of years and can offer the following observations. Prior to starting any such voluntary program, it is essential that a firm decision be made as to what will be done with a positive result. It is not enough to say that the individual will be retested. An immediate decision must be made regarding clinical privileges and, if privileges are continued, to whom the liability falls for allowing an individual who is now "suspect" to continue in practice should an untoward event occur. Reliability of a drug testing program falls not only on the laboratory, a complex situation in itself,
Extrathymic Aire-Expressing Cells Are a Distinct Bone Marrow-Derived Population that Induce Functional Inactivation of CD4+ T Cells
Authors: James M. Gardner, Todd C. Metzger, Eileen J. McMahon, Byron B. Au-Yeung, Anna K. Krawisz, Wen Lu, Jeffrey D. Price, Kellsey P. Johannes, Ansuman T. Satpathy, Kenneth M. Murphy, Kristin V. Tarbell, Arthur Weiss, Mark S. Anderson
Journal: Immunity (2013)
Orlistat: should we worry about liver inflammation?
Authors: J. Wilding
Journal: BMJ (2013)

Events are rare and a causal link unproved; still a useful option for some obese patients 

In a linked paper (doi:10.1136/bmj.f1936), Douglas and colleagues used data from the UK Clinical Practice Research Datalink and Hospital Episodes Statistics to explore the possible association between orlistat use and abnormalities of liver function in 94 695 patients who received orlistat over a 12 year period.1 Orlistat is an inhibitor of intestinal and pancreatic lipases that was first licensed for the treatment of overweight and obesity in 2008 and became available in the United Kingdom in 2009. It is currently the only prescription drug available for the treatment of obesity and is also available over the counter in a lower strength form, with slightly reduced efficacy. The drug acts within the gastrointestinal tract and less than 1% is absorbed systemically. As a result, circulating concentrations of orlistat are low (<0.02 μmol/L), and at this concentration it has no systemic effects on other lipases.

A meta-analysis of more than 10 000 patients in clinical trials showed a mean placebo subtracted weight loss of 2.9 kg over 12 months of treatment.2 Weight loss was maintained long term for subjects in one study, as long …
Studies on Acquired Hypogammaglobulinemia
Authors: Theophilus S. Painter, Donald R. Korst
Journal: New England Journal of Medicine (1959)

PRIMARY hypogammaglobulinemia or agammaglobulinemia has received considerable attention since the original description by Bruton1 in 1952. Good2 3 4 5 has written extensively on this subject and has defined the condition as a metabolic disorder featured by an enhanced susceptibility to bacterial infection, absence of gamma globulin from the serum, absence of antibodies from blood and tissues and failure of immunologic response to antigenic stimulation. There are two types: the congenital,6 which is a sex-linked mendelian recessive disorder, occurs in males and is manifested early in childhood; and the adult or acquired primary type, which is diagnosed in adult life, occurs in both . . .
Influence of postoperative empyema on survival after pulmonary resection for bronchogenic carcinoma.
Authors: H Minasian, C T Lewis, S J Evans
Journal: BMJ (1978)

Fifty patients who had developed empyema after pulmonary resection for primary carcinoma of the lung were individually paired with patients who had not suffered this complication. Pairs were matched as far as possible for age, sex, extent of operation, histology of tumour, extent of primary spread, extent of lymphatic spread, and use of postoperative radiotherapy. Analysis of survival times both for the matched pairs and for the two groups of patients showed no significant difference in long-term survival. The results suggest that any immunological suppression of carcinoma cells due to sepsis in the pleural space is ineffective in prolonging survival.
S66 The Gli Spirometry Reference Equations Influence The Apparent Rate Of Decline In Fev1 Among Children And Adolescents With Cystic Fibrosis
Authors: G. Davies, P. Aurora, A. McDonald, A. Prasad, D. Bilton, J. Stocks, S. Stanojevic
Journal: Thorax (2014)

<h3>Background</h3> In patients with cystic fibrosis (CF), interpretation of cross-sectional FEV<sub>1</sub> data is greatly influenced by choice of spirometry reference equation, particularly during childhood (Stanojevic; J Cyst Fibros 2014). We hypothesised that availability of the Global Lung Function Initiative (GLI) spirometry reference equations (Quanjer; ERJ 2012) will also affect the apparent rate of decline in lung function over time, thereby potentially altering our understanding of disease progression in CF. <h3>Methods</h3> Data were extracted from two patient registries: the UK CF Registry (n = 6043 subjects; 20,013 test occasions over a period of 5 years) and the Toronto CF database (n = 1023 subjects; 27,868 test occasions over a period of 23 years). Spirometric outcomes were interpreted using%predicted FEV<sub>1</sub> calculated from GLI, Knudson (as currently used by the UK CF Registry), and Wang-Hankinson (as used by the US CF Foundation) reference equations. Patients &gt;30 yrs or with FEV<sub>1</sub> &gt; 130% predicted were excluded. We used a non-linear mixed effects model to describe the average change in FEV<sub>1</sub> with age. To illustrate the importance of reference equation in evaluating risk factors, FEV<sub>1 </sub>decline according to patient gender was also explored. <h3>Results</h3> The pattern of lung function decline at the population level differed according to selected equation (Figure). Average rate of decline was steeper with Knudson or Wang-Hankinson than GLI. Importantly, GLI equations showed a steady decline in FEV<sub>1</sub> starting at 6 yrs, whereas the other equations suggest greater decline during adolescence. Similar patterns were observed in both UK and Toronto populations. When analysed according to gender, the rate of lung function decline was steeper in females during early adolescence compared with males where the decline was steady. <h3>Conclusions</h3> In both datasets, Knudson and Wang-Hankinson reference equations suggest relative preservation of spirometry in childhood followed by rapid decline in adolescence. However using the more robust GLI equations, steady decline throughout childhood with a less dramatic acceleration during adolescence is seen, with differences in pattern of change over time according to patient gender. Accurate identification of critical periods of lung function decline offers novel opportunities to target care. Funded by the UK CF Trust.
BRACHIAL-ANKLE PULSE WAVE VELOCITY CORRELATED WITH AN ENDOTHELIUM-INDEPENDENT VASODILATION IN CONDUIT CORONARY ARTERY
Authors: Takuro Kubozono, Masaaki Miyata, Sanemasa Ishida, Tetsuro Kataoka, Akiko Yoshikawa, Naoya Oketani, Hideki Okui, Takuro Shinsato, So Kuwahata, Hitoshi Ichiki, Shoji Fujita, Satoshi Yoshino, Daisuke Kanda, Osamu Fukumoto, Shuichi Hamasaki, Chuwa Tei
Journal: Journal of the American College of Cardiology (2010)
Safety of air travellers is not protected
Authors: H Swire
Journal: BMJ (1996)

EDITOR,—The Scott report reveals “Whitehall secrecy and deceit…advancing the interests of major industrial concerns even when they mislead parliament and the public in doing so.”1 Here is another example showing how industrial concerns have misled parliament and contributed to the deaths of 270 people.

In 1985 an Air India jet was lost off …
A North West Europe chapter of F.I.M.S?
Authors: H. E. Robson, M. R. Melamed
Journal: British Journal of Sports Medicine (1980)

On the initiative of the Swedish Society of Sports Medicine, an invitation was sent late in 1979 to similar societies in Scandinavia, West Germany, Holland and the United Kingdom to meet in Sweden and discuss sports medicine problems common to these countries, but different from the situation in the Latin countries, Asia, and Eastern Europe.The meeting took place in Ystad in the extreme South of the country on May 28th and 29th, 1980, and was followed immediately by the Swedish society's annual residential meeting, for which we were invited to remain and participate.Some 25 delegates attended the preliminary meeting, and around 250 the society's Symposium.The Saltsjobad Hotel was well equipped to hosue conferences, with a lecture theatre which could house the 250 easily, and other committee rooms for smaller groups and for the trade exhibition held in connection with the symposium.Although there were only four representatives from Britain, BASM was well represented, as another six of our over- seas members came with other delegations.Apart from the business of the first two days, opportunities were made to see some of the county of Skane, once a Danish possession, and still retaining some of the traditions of the Danes and of the many Scottish emigres who came over after the '45, and in subsequent years, and made an impact on the business and agriculture of the region.
β-Endorphin and cortisol abnormalities in spinal cord-injured individuals
Authors: Joan A. Culpepper-Morgan, Donna J. Twist, Claudio R. Petrillo, Kenneth M. Soda, Kreek Mary Jeanne
Journal: Metabolism (1992)

Plasma β-endorphin-like immunoreactivity (BEP-ir) and cortisol levels were measured by radioimmunoassay (RIA) in nine patients who were at least 12 months status post spinal cord injury (SCI). Plasma levels were obtained at 8:00 am and 4:00 pm to determine circadian rhythm, and on the day following administration of 1 mg dexamethasone, levels were again obtained at 8:00 am and 4:00 pm. The mean morning levels of plasma BEP-ir were significantly lower than control values for this laboratory (6.2 ± 1.2 v 12.0 ± 2.3 pg/mL). The morning BEP-ir values were lowest in patients who were closer to the time of injury (described by a second-order polynomial regression, R = .89; P < .01). Mean morning cortisol levels were not significantly different from controls, but showed greater variability (mean, 15.1; range, 0.7 to 22.7 μg/dL v control, 15.5; range, 7 to 35). Dexamethasone suppressed cortisol secretion in all patients and BEP-ir levels in six of nine patients. Failure to detect BEP-ir suppression occurred in patients whose BEP-ir levels were less than 4.5 pg/mL and close to the minimum detection limit of the assay. Depression was present in five of nine patients as measured by the Beck Depression Inventory (BDI) and in three of nine patients as measured by the Hamilton Depression Scale (HSRD). However, the depression indices did not correlate with the neuroendocrine measures.
Antigen-dependent CD28 Signaling Selectively Enhances Survival and Proliferation in Genetically Modified Activated Human Primary T Lymphocytes
Authors: Anja Krause, Hong-Fen Guo, Jean-Baptiste Latouche, Cuiwen Tan, Nai-Kong  V. Cheung, Michel Sadelain
Journal: The Journal of Experimental Medicine (1998)

Most tumor cells function poorly as antigen-presenting cells in part because they do not express costimulatory molecules. To provide costimulation to T lymphocytes that recognize tumor cells, we constructed a CD28-like receptor specific for GD2, a ganglioside overexpressed on the surface of neuroblastoma, small-cell lung carcinoma, melanoma, and other human tumors. Recognition of GD2 was provided by a single-chain antibody derived from the GD2-specific monoclonal antibody 3G6. We demonstrate that the chimeric receptor 3G6-CD28 provides CD28 signaling upon specific recognition of the GD2 antigen on tumor cells. Human primary T lymphocytes retrovirally transduced with 3G6-CD28 secrete interleukin 2, survive proapoptotic culture conditions, and selectively undergo clonal expansion in the presence of an antiidiotypic antibody specific for 3G6-CD28. Polyclonal CD8+ lymphocytes expressing 3G6-CD28 are selectively expanded when cultured with cells expressing allogeneic major histocompatibility complex class I together with GD2. Primary T cells given such an antigen-dependent survival advantage should be very useful to augment immune responses against tumor cells.
Unilateral Arcus Corneae Senilis and Carotid Occlusive Disease
Authors: Sharwan K. Bagla
Journal: JAMA (1975)

ARCUS corneae senilis, a lipid infiltration in the corneoscleral junction of the eyes, is considered to be part of the natural process of aging,<sup>1</sup>and might be expected, therefore, to appear in both eyes. However, Smith and Susac<sup>2</sup>reported a patient who had a severe arcus corneae senilis in the right eye only, with a history of amaurosis fugax in the left eye. Autopsy disclosed a large plaque virtually occluding the lumen of the left internal carotid artery, while the right side was patent. The arcus appeared on the side opposite the carotid occlusion. We wish to report a second case of unilateral arcus corneae in a patient with ophthalmodynanometric evidence of contralateral carotid artery insufficiency. <h3>Report of a Case</h3> A 52-year-old woman with diabetes, peripheral neuropathy, and arteriosclerotic heart disease came to the Northport Veterans Administration Hospital for treatment of a urinary tract infection. She had been
Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma
Authors: Patrick A. Ott, Omid Hamid, Anna C. Pavlick, Harriet Kluger, Kevin B. Kim, Peter D. Boasberg, Ronit Simantov, Elizabeth Crowley, Jennifer A. Green, Thomas Hawthorne, Thomas A. Davis, Mario Sznol, Patrick Hwu
Journal: Journal of Clinical Oncology (2014)

The antibody-drug conjugate glembatumumab vedotin links a fully human immunoglobulin G2 monoclonal antibody against the melanoma-related glycoprotein NMB (gpNMB) to the potent cytotoxin monomethyl auristatin E. This study evaluated the safety and activity of glembatumumab vedotin in patients with advanced melanoma.Patients received glembatumumab vedotin every 3 weeks (schedule 1) in a dose escalation and phase II expansion at the maximum-tolerated dose (MTD). Dosing during 2 of 3 weeks (schedule 2) and weekly (schedule 3) was also assessed. The primary end points were safety and pharmacokinetics. The secondary end points included antitumor activity, gpNMB expression, and immunogenicity.One hundred seventeen patients were treated using schedule 1 (n = 79), schedule 2 (n = 15), or schedule 3 (n = 23). The MTDs were 1.88, 1.5, and 1.0 mg/kg for schedules 1, 2, and 3, respectively. Grade 3/4 treatment-related toxicities that occurred in two or more patients included rash, neutropenia, fatigue, neuropathy, arthralgia, myalgia, and diarrhea. Three treatment-related deaths (resulting from pneumococcal sepsis, toxic epidermal necrolysis, and renal failure) occurred at doses exceeding the MTDs. In the schedule 1 phase II expansion cohort (n = 34), five patients (15%) had a partial response and eight patients (24%) had stable disease for ≥ 6 months. The objective response rate (ORR) was 2 of 6 (33%) for the schedule 2 MTD and 3 of 12 (25%) for the schedule 3 MTD. Rash was correlated with a greater ORR and improved progression-free survival.Glembatumumab vedotin is active in advanced melanoma. The schedule 1 MTD (1.88 mg/kg once every 3 weeks) was associated with a promising ORR and was generally well tolerated. More frequent dosing was potentially associated with a greater ORR but increased toxicity.
Phosphorus-31 magnetic resonance spectroscopy of the human liver using chemical shift imaging techniques
Authors: I.Jane Cox, David K. Menon, Janet Sargentoni, David J. Bryant, Alan G. Collins, Glyn A. Coutts, Richard A. Iles, Jimmy D. Bell, I.S. Benjamin, Stephen Gilbey, Humphrey J.F. Hodgson, Marsha Y. Morgan
Journal: Journal of Hepatology (1992)
Eccentric atherosclerotic plaques with positive remodeling have a pericardial distribution: A permissive role of epicardial fat—A three-dimensional intravascular ultrasound study of left anterior descending artery lesions
Authors: Francesco Prati, Eloisa Arbustini, Antonella Labellarte, Luigi Sommariva, Tomasz Pawlowski, Alessandro Manzoli, Aneta Gziut, Eugenio Caradonna, Alessandro Boccanelli
Journal: Journal of the American College of Cardiology (2003)