tbuckley/cabot-search huggingface dataset:
Comparative trial of BBR 2778 (pixantrone) + rituximab vs single agent rituximab in the treatment of relapsed/refractory indolent non-Hodgkin’s lymphoma (NHL)
Authors: A. Santoro, J. Voglova, N. Gabrail, T. Ciuleanu, M. Liberati, B. W. Hancock, S. Stromatt, D. Caballero
Journal: Journal of Clinical Oncology (2006)

7578 Background: BBR 2778 is a novel aza-anthracenedione that shows structural similarities to the anthracyclines, demonstrates single agent activity in patients with NHL, and does not exhibit cardiotoxic effects in animal models. This phase III open-label study was designed to compare the efficacy and tolerability of combination rituximab and BBR 2778, with that of single agent rituximab, in patients (pts) with relapsed or refractory indolent NHL. Methods: Pts were randomly assigned to receive both rituximab and BBR 2778 (experimental arm), or rituximab alone (control arm). In the experimental arm, pts received 375 mg/m 2 rituximab IV on days 1 and 8 of cycles 1 and 2 only, and 90 mg/m 2 BBR 2778 IV on days 2 and 8 of cycle 1, and on days 1 and 8 of all subsequent cycles. Pts could receive six 21-day cycles of BBR 2778. In the control arm, pts received 375 mg/m 2 rituximab IV on days 1, 8 and 15 of cycle 1 and day 1 of cycle 2 only. Disease response was assessed every other cycle according to International Workshop to Standardize Response Criteria for NHL. Toxicities were assessed throughout the study using NCI-CTC criteria. Study was closed early due to poor enrollment. Results: 38 pts (20 experimental, 18 control) were enrolled. Mean age was 66 and 59 years in the experimental and control arm, respectively. Most patients were males and most had ECOG performance status 0 or 1. Efficacy is summarized in the table. Response rate (75 vs 33%) and time to progression (13.2 vs 8.1 months) were better in the BBR 2778 arm. Only pts in the experimental arm had study drug related serious adverse events (2 febrile neutropenia, 1 pneumonia, 1 neutropenia) and adverse events resulting in withdrawal (6 vs 0). Conclusions: Combination of BBR 2778 and rituximab is superior to rituximab alone with regard to time to progression and overall response rate. BBR 2778 combined with rituximab appeared to be a generally well tolerated regimen in patients with relapsed/refractory indolent NHL. [Table: see text] [Table: see text]
Hopes rise for new Alzheimer’s drug after secondary analysis:
Authors: Nigel Hawkes
Journal: BMJ (2015)

Data from a failed trial of a drug for Alzheimer’s disease have generated a slim hope that it was not such a failure after all.

When the drug manufacturer Eli Lilly reported the results of its phase III trial of solanezumab in 2012, it looked like the end. The monoclonal antibody drug had failed to improve either cognitive or functional endpoints in patients with mild to moderate disease. Along with several other drugs that target amyloid β—the protein that forms clumps in the brains of Alzheimer’s patients—solanezumab had been a disappointment.

This week, however, the company announced new results from a secondary analysis of the trial data that suggested a small, sustained effect in patients with mild disease. The original trial lasted 18 months and compared treatment against placebo, followed by a two year period in which patients on a placebo were transferred to the drug. This allowed a comparison between the early …
Phenylephrine-Induced Reversible Cataract in the Mouse
Authors: C M P Claoué
Journal: Journal of the Royal Society of Medicine (1987)

Topical 10% phenylephrine will produce lens opacities in several strains of mouse. These lens opacities resolve spontaneously within 24 hours, leaving an apparently normal eye. Phenylephrine-induced lens opacification in the mouse can be prevented by covering the eye with ointment, suggesting that the underlying mechanism is transcorneal dehydration.
Abstract 301: Deletion of Sam68 Attenuates Myocardial Hypertrophy
Authors: Junlan Zhou, Chan Boriboun, Dauren Biyashev, Gangjian Qin
Journal: Circulation Research (2014)

The Src-associated in mitosis 68 kDa (Sam68) belongs to the STAR (signal transducer and activator of RNA) family of RNA-binding proteins and has recently been shown to regulate angiotensin II (Ang II) signaling in vascular smooth muscle cells. In this study, we investigated the role of Sam68 in cardiac hypertrophy. Wild-type (WT) and Sam68 knockout (KO) mice were administered continuously with Ang II for 14 days via osmotic minipumps. Echocardiography analyses reveled that basal left-ventricular posterior wall thicknesses (LVPTs and LVPTd) and basal chamber sizes (LVIDs and LVIDd) are similar between the 2 groups of mice, that Ang II induced a significant elevation in LVPTs and LVPTd and reduction in LVIDs and LVIDd in both groups of mice, and that the changes of all these hypertrophic parameters were significantly attenuated in Sam68 KO than in WT mice (p&lt;0.05 at day 14, n=15). The increase in the heart weight (HW) / body weight (BW) ratio was also lesser in Sam68 KO mice than in WT mice (p&lt;0.05 at day 14, n=15). Then, we performed transverse aortic constriction (TAC) model. Echocardiography analyses confirmed significantly lower levels of LVPTs/d and LVIDs/d in Sam68 KO mice than in WT mice (LVPTs/d: p&lt;0.05 at weeks 2 and 4, p&lt;0.01 at weeks 8; LVIDs/d: p&lt;0.05 at weeks 2, 4, and 8; n=12), however, left ventricular ejection fraction (LV EF) remained not significantly different at all these time points between the 2 groups. Histological analyses of fibrosis by Masson’s trichrome staining demonstrated a ~ 2-fold less in collagen deposition areas in Sam68 KO than in WT mice (p&lt;0.05 at weeks 8, n=12). The attenuated hypertrophic responses of Sam68 KO mice to both Ang II treatment and TAC surgery was further supported by a lower expression of fetal genes, including β-myosin heavy chain, atrial and brain natriuretic peptides in the heart of Sam68 KO mice than in WT mice (qRT-PCR). Collectively, our results suggest that Sam68 may modulate the cause of cardiac hypertrophy
Factors influencing quality of life in patients with inherited ichthyosis: a qualitative study in adults using focus groups
Authors: J. Mazereeuw-Hautier, I. Dreyfus, S. Barbarot, L. Serrentino, E. Bourdon-Lanoy, K. Ezzedine, A. Maza, I. Aujoulat, A. Le Rhun
Journal: British Journal of Dermatology (2011)

There is limited information regarding quality of life in patients with inherited ichthyosis.To identify factors influencing quality of life in patients with inherited ichthyosis.The study used focus groups and involved adult patients suffering from inherited ichthyosis from three French hospital centres. Group discussions were conducted by two facilitators and were continued until data saturation was reached. The verbatim transcripts were analysed independently by two investigators. Categories considered as key factors in the modulation of quality of life were negotiated until agreement was obtained.Data saturation was reached after the fifth group. A total of 25 patients affected by various forms of ichthyosis attended these focus groups. The identified factors influencing quality of life were related to physical health, daily life, relations with others or oneself. However, together with difficulties related to ichthyosis, patients also underlined some positive aspects of the disease and described specific measures used to improve their quality of life.This is the first study investigating the different factors that could impact quality of life in patients with ichthyosis. This provides an essential framework from which physicians can develop strategies to improve patient care and quality of life and to develop a specific quality of life questionnaire.
IMMUNOHISTOLOGIC STUDIES OF SYNOVIOCYTES AND SYNOVIAL EXUDATE CELLS
Authors: Eric R. Hurd, T. Douglas Kinsella, Morris Ziff
Journal: The Journal of Experimental Medicine (1971)

Inclusions were demonstrated in normal polymorphonuclear cells incubated with rheumatoid factor-positive synovial fluid. These stained positively for IgG, IgM, and the ß1C component of complement. When normal polymorphonuclear cells were incubated with factor-negative rheumatoid fluid, inclusions were not obtained. However, after addition of IgM rheumatoid factor to such fluids, discrete inclusions were observed with similar staining properties. In a minority of nonrheumatoid fluids, inclusions were also obtained after addition of IgM rheumatoid factor. The phagocytosis of inclusions from synovial fluids after addition of IgM rheumatoid factor suggests the presence of aggregated IgG in these fluids. Immunofluorescent staining of phagocytic synovial lining cells, isolated from synovial tissue by trypsin digestion, demonstrated a diffuse staining pattern for IgG and the ß1C component of complement in cells from both seropositive and seronegative patients. In seropositive patients, discrete inclusions were also observed which stained positively for IgG, IgM, and ß1C. These findings provide evidence of in vivo phagocytosis of immune complexes from the synovial fluid.
Personal views: Genetic information and the unexamined life
Authors: John Harris
Journal: BMJ (2001)

There is no right to genetic information nor to access to particular tests. Doctors may need persuading that particular tests are in patients' best interests, and usually such tests are for serious genetic conditions of which there is an established family history. Lack of resources may limit access, but even so called “over-the-counter” or postal tests require licences. In the United Kingdom, the provision of tests has to comply with various codes of practice and guidance, issued by such bodies as the Advisory Committee on Genetic Testing, the Human Fertilisation and Embryology Authority, and the Human Genetics Commission, and it is strictly controlled.

Despite this it is difficult to imagine on what basis people might be denied information about themselves, or might be denied the opportunity to seek that information. There are three powerful reasons why people are entitled to genetic information.


The first and most obvious reason is simply that any genetic information about myself is mine. It is information about me, generated from my DNA. Suppose I could find out this information just by looking in the mirror—would I be wrong to look? If my sight were not sufficiently acute to see the fine detail, would you be wrong to do it for me at my request? How could the fact that I need to rely on medical science for the information change my entitlement to it? 


Genetic information may help me to make rational decisions about my life and priorities




The second reason is that some of this information is medical information. We have surely now established, after long and persistent ethical argument, that patients are entitled to be told the truth if that is what they want. How could “truth” that must be revealed by a test differ from truth already known (except in so far as scarce resources dictate other priorities)? 




The third reason is that respect for autonomy demands it. Genetic information may help me to make rational decisions about my life and priorities. To deny me information which I might need for rational, autonomous decision making is to deny me the most basic and ultimate form of respect. To deny people genetic information that could inform decision making and planning for the future would go against the whole ethos of informed consent so recently endorsed in the aftermath of the Alder Hey inquiry.
Planned Parenthood accuses anti-abortion group of “corporate espionage” for promoting misleading video
Authors: Owen Dyer
Journal: BMJ (2015)

The Planned Parenthood Federation of America this week warned that an undercover video edited to suggest wrongly that the group sold fetal body parts for profit may be the first of many, as the group that released it has been posing as a legitimate biomedical research supply firm for three years.

The nine minute video, cut from three hours, shows a lunchtime restaurant meeting between Planned Parenthood’s chief medical officer, the physician Deborah Nucatola, and two actors with hidden cameras posing as executives from a fake company called Biomax seeking fetal tissue for supply to research institutions.1

In the video Nucatola describes techniques used to remove fetuses without damaging organs donated for research, in cases where parents have signed a consent form. As with hospitals’ organ donations, the clinic generally charges a fee to recoup storage and transport costs. During the video one actor asks about “pricing” of organs, …
Immunoglobulin‐free light chain monomer‐dimer patterns help to distinguish malignant from premalignant monoclonal gammopathies: A pilot study
Authors: Batia Kaplan, Sizilia Golderman, Boris Aizenbud, Konstantin Esev, Olga Kukuy, Merav Leiba, Avi Livneh, Ilan Ben‐Zvi
Journal: American Journal of Hematology (2014)

Multiple myeloma (MM) and AL amyloidosis (AL) are two malignant forms of monoclonal gammopathies. For the purposes of prognosis and treatment, it is important to distinguish these diseases from the premalignant forms of monoclonal gammopathies, such as monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma (SMM). Routine serum/urine tests for monoclonal protein are insufficient for differential diagnosis. Thus, invasive procedures, such as tissue aspiration or biopsy, are applied. In this study, we aimed at characterization of serum-free light chain (FLC) monomer-dimer patterns to distinguish the malignant from the premalignant forms of monoclonal gammopathies. A quantitative Western blotting was applied to estimate the FLC monomer and dimer levels in AL, MM, MGUS, and SMM patients, and in control subjects (healthy individuals and patients with AA amyloidosis). AL and MM patients displayed an abnormally increased dimerization of monoclonal FLC, accompanied by higher clonality values of FLC dimers, as compared to that of monomers. These abnormalities of FLC patterns were not observed in patients with MGUS, SMM, AA amyloidosis, and healthy individuals. Analysis of FLC patterns helped to differentiate AL and MM from MGUS and SMM, a goal difficult to achieve using routine serum tests. Also, our technique might serve as a complimentary diagnostic tool in the cases with suspected AL amyloidosis, where the diagnosis of MM is excluded, while the results of amyloid typing by routine immunohistochemical techniques are inconclusive.
Efficacy and Safety Of Ponatinib Following Failure Of Dasatinib In Patients (pts) With Chronic Phase Chronic Myeloid Leukemia (CP-CML) In The PACE Trial
Authors: Andreas Hochhaus, Jorge E. Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Philipp D le Coutre, Ronald Paquette, Charles Chuah, Franck E. Nicolini, Jane F Apperley, H. Jean Khoury, Moshe Talpaz, John F. DiPersio, Daniel J DeAngelo, Elisabetta Abruzzese, Delphine Rea, Michele Baccarani, Martin C. Müller, Carlo Gambacorti-Passerini, Stephanie Lustgarten, Victor M. Rivera, Tim Clackson, Christopher D Turner, Frank G Haluska, Michael W. Deininger, Timothy P. Hughes, John M Goldman, Neil P. Shah, Hagop M. Kantarjian, François Guilhot
Journal: Blood (2013)
Methods of examining induced sputum: do differences matter?
Authors: JC Kips, RA Peleman, RA Pauwels
Journal: European Respiratory Journal (1998)

Analysis of induced sputum has been proposed as a direct, relatively noninvasive method for the evaluation of airway inflammation in diseases such as asthma or chronic obstructive pulmonary disease (COPD). An important question in the validation of this technique concerns the potential influence of differences in the methods of examining sputum. Up to the present time, two basic techniques for processing sputum have been described. The first approach consists of selecting all viscid portions from the expectorated sample, whereas the second approach processes the whole expectorate, containing sputum plus saliva. Both processing techniques have been shown to provide valid and reliable data on the composition of the cellular and soluble fraction of induced sputum. From the data currently available, it would therefore appear that the usefulness of induced sputum as a method for assessing airway inflammation is not influenced by differences in the methods currently used for examining sputum.
Palliative treatment with gefitinib (G) in advanced and heavy pre-treated non-small cell lung cancer (NSCLC)
Authors: E. Tamburini, S. Nicoletti, M. Papi, M. Fantini, C. Possenti, E. Pasquini, M. Nicolini, P. Fabbri, P. Fattori, D. Tassinari, A. Ravaioli
Journal: Journal of Clinical Oncology (2006)

17139 Background: G has demonstrated to be active in patients with advanced NSCLC pretreated with chemotherapy. We report our experience about activity and safety of G in patients with advanced, heavily pre-treated NSCLC or chemotherapy-naive patients with a low performance status. Methods: The records of the patients treated with G were reviewed; all the patients pre-treated with at least one course of a platinum-containing regimen or with low performance status were considered eligible and enrolled in the trial. All the patients were treated with G 250 mg/die until progression of the disease or intractable toxicity. All the patients were evaluated every 21 days for toxicity and every 2 months for survival. Primary end point was time to progression (TTP); secondary ones were overall survival (OS) and safety. Results: Till today 56 patients were considered eligible and enrolled in the trial; the results are summarised in the table . *: using Kaplan-Meyer test. No significant differences in OS were observed between the patients chemotherapy-naive with low performance status or pre-treated with one line of chemotherapy vs heavily pretreated ones (respectively 170 days vs 120 days, p = 0.85 using the Log-Rank test). Toxicity was mild with no haematological side effects and grade IV diarrhoea in 1 patient (1.7%). Conclusions: G seems to represent an interesting option in patients with NSCLC with low performance status or heavily pre-treated with chemotherapy. Our data seem to confirm that G is an active and safe treatment in such a subset of patients, opening a novel dimension in the treatment of pre-treated NSCLC (supported by IOR). [Table: see text] No significant financial relationships to disclose.
Abstract 16751: Prevalence and Outcome of Cardiogenic Shock in Patients With Takotsubo Cardiomyopathy
Authors: Birke Schneider, Anastasios Athanasiadis, Johannes Schwab, Wolfgang Pistner, Uta Gottwald, Wolfgang Toepel, Tobias Muller-Honold, Ralph Schoeller, Claudia Stollberger, Udo Sechtem
Journal: Circulation (2013)

Purpose: Tako-tsubo cardiomyopathy (TTC) is regarded a benign disease since left ventricular (LV) function returns to normal within a short period of time. However, severe complications have been d...
Weight loss during concomitant chemo-radiation therapy for squamous cell head and neck cancer: Possible role of transient hyperthyroidism
Authors: B. Mehrotra, A. Caramalis, S. Nissel-Horowitz, N. Radhakrishnan, J. Marsh, S. Limaye
Journal: Journal of Clinical Oncology (2007)

16531 Background: Concomitant Chemoradiotherapy (CRT) is a standard treatment modality for locally advanced squamous cell head and neck cancer (HNC). This treament is often associated with significant weight loss which is commonly attributed to nutritional depletion secondary to mucositis, pain and inadequate oral intake. We undertook an evaluation of thyroid function as measured by Thyroid Stimulating Hormone (TSH) levels during CRT to evaluate the possible role of a thyroid hormone flare during treatment that may account for part of this weight loss. Methods: Institutional Review Board approval was obtained to conduct this retrospective analyses. Patients treated at our institution during the past six months who were treated with CRT for HNC and had recorded TSH levels at baseline (when available), mid treatment (week 4 to 6 of CRT), and post CRT (6 to 9 weeks later), at least 5% weight loss during treatment, and feeding tube requirement data available were identified. Age, Gender, Stage and Primary site of disease, Radiation dose and fields, chemotherapy regimen, were recorded. Results: Twelve patients were identified. Mid treatment TSH levels were suppressed below normal reference range (0.49–4.67 mIU/L) in 7of 12 pts (58%). A decline in TSH levels was noted in all 8 of 8 pts (100%) that had recorded pre-CRT TSH levels and mid treatment levels. Improvement of TSH levels was noted in all 9 of 9 patients that had mid treatment and post treatment TSH levels recorded, although in three of these nine patients TSH levels remained below normal range. Four of twelve pts required PEG placements for nutritional support. Conclusions: Transient suppression of TSH levels suggesting a thyroid flare is frequently observed early during CRT for HNC and appears to improve by 6–9 weeks post treatment. This may contribute to weight loss in this nutritionally challanged population. Further studies evaluating more specialised thyroid function testing to exclude sick euthyroid states and other etiologies for suppressed TSH levels are warranted. In addtion, therapeutic methods to abbrogate this flare may reduce weight loss during aggressive CRT treatment protocols. No significant financial relationships to disclose.
Biomarkers associated with seminal vesicle involvement and chemical recurrence after radical prostatectomy
Authors: J. P. Fruehauf, D. W. Skarecky, T. E. Ahlering
Journal: Journal of Clinical Oncology (2005)

4691 Background: A concern of prostate cancer patients treated with radical prostatectomy is the likelihood of future metastatic progression. We investigated the association between clinical predictors of outcome with angiogenesis biomarkers to assess their role in cancer recurrence. Methods: IRB approval was obtained to collect material for 156 men who underwent radical prostatectomy at our institution. Univariate analysis and multivariate analysis was performed for men dead or dying of metastasis. Clincal factors included age, pre-operative PSA, Gleason score, lymph node involvement and seminal vesicle status. Biomarkers included androgen receptor, Ki67, mutant p53, CD117 (cKit), CD31 vessel densities, TSP-1 expression and VEGF expression. Results: Men aged ≤ 60 had significantly faster PSA rise and shorter time to initial rise (p<.012). Tumors from men aged 60 or less had decreased levels of the angiogenesis suppressor protein TSP-1, but also had significantly lower levels of VEGF. Linear regression demonstrated a significantl association between age, TSP-1 (p=0.017), and VEGF intensity (p=0.004). In univariate analysis seminal vesicle involvement was associated androgen receptor staining percentage and intensity (AR p<.02), mutant P53 (p=.008), Ki67 percentage (p=.000), and CD117 percentage and intensity (p=.002-.06). Multivariate analysis demonstrated that seminal vesicle positive was significantly associated with CD117 intensity (p=0.0045) and Ki67 intensity (p=0.058). Conclusions: Younger men who underwent radical prostatectomy had earlier recurrences (p<.012). This age group also had significantly lower levels of TSP-1 and VEGF. The angiogenic switch may be related to the ratio between these two factors rather than their absolute values. Markers Ki67, mutant P53, CD31 and androgen receptor were not associated with earlier onset or recurrence. Seminal vesicle involvement was highly associated with CD117 expression and Ki67. CD117 may be a prognostic factor in prostate cancer. Newer antiangiogenesis agents inhibit both VEGF-receptor and CD117, and should be evaluated to determine if they can delay the time to progression in younger men at risk for prostate cancer recurrence. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncotech Oncotech