tbuckley/cabot-search huggingface dataset:
Retrospective analysis of Japanese patients with relapse or refractory small-cell lung cancer (SCLC) treated with amrubicin hydrochloride.
Authors: Y. Kim, T. Mio, K. Masago, K. Irisa, Y. Sakamori, M. Mishima
Journal: Journal of Clinical Oncology (2010)

e18088 Background: Amrubicin (AMR) is one of the most active chemotherapeutic agents for small-cell lung cancer (SCLC), and its effectiveness and severe hematologic toxicities have been reported in previous phase II studies; however to date, it is not approved outside Japan and there is no extensive evidence of its effects. Methods: Between January 2004 and October 2009, 69 patients received AMR for relapsed SCLC in our hospital. We reviewed these patients and analyzed the efficacy and hematologic toxicities of AMR. Patients who responded to initial chemotherapy and relapsed more than 3 months after chemotherapy were defined as sensitive relapse (S), while patients who did not respond to initial chemotherapy or relapsed within 3 months were defined as refractory relapse (R). Results: There were 27 S and 42 R. All patients had received platinum agents, and 43% and 71% patients had received etoposide and irinotecan, respectively. The median number of treatment cycles was 3 (range, 1–14), and the response rate was 51% (70% in S and 38% in R, respectively). In patients administered AMR as the second-line therapy, the response rate was 55%, and as the third-line therapy, 39%. Median progression-free survival time was 3.2 months in S and 1.9 months in R (p = 0.1071). Median survival time from the start of AMR was 6.2 months in S and 4.8 months in R (p = 0.0045). The frequency of grade ≥ 3 hematologic toxicities was leukopenia (41%), neutropenia (51%), anemia (14%), thrombocytopenia (17%), and febrile neutropenia (12%). No treatment-related death was observed. Conclusions: Although hematologic toxicities, especially neutropenia, were severe, AMR showed excellent anti-tumor activity not only in S but also in R, as shown in previous phase II studies. These results warrant further evaluation of AMR in the second-line setting, and also in the first-line setting in both limited- and extensive-stage disease. We are now conducting a phase II study to assess the efficacy of consolidation chemotherapy with AMR after standard chemoradiation in limited-stage SCLC. No significant financial relationships to disclose.
Primary Human Breast Carcinomas Transplantable in the Nude Mouse&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Sebesteny, J Taylor-Papadimitriou, R Ceriani, R Millis, C Schmitt, D Trevan
Journal: JNCI Journal of the National Cancer Institute (1979)

Of 19 primary human breast carcinomas implanted into noninbred female nude mice, 3 produced transplantable tumors. Membrane components specific for human mammary epithelial cells were demonstrated in the cells from heterotransplants even after four or five passages in nude mice.
Carbon in the airway macrophages of children affected by chronic lower airway disease
Authors: Deborah Snijders, Laura Bottecchia, Veronica Storer, Erika Bazzan, Elena Mutti, Serena Calgaro, Angelo Barbato
Journal: European Respiratory Journal (2012)

The effect of air pollution can play a role in the development and/or the exacerbations of chronic lower airway diseases (CLADs) in children.  The aim of this study is to investigate the association between the major component of inhalable particulate matter (PM10), black carbon, contained in lower airway macrophages (AM) of children with CLADs and variables that may affect individual exposure.  We studied 24 children undergoing FOB for CLADs. For each child the area of the black material (BM) in AMs, sampled by bronchoalveolar lavage, was determined by analysis of digitized light microscopic images of random AMs; median carbon content of AMs was obtained calculating the area (µm 2 ) of BM.  Children had a median age of 6 years (range 2,9-16,6); they were affected by recurrent lower airways infections in 12 cases (PCD in 2), by asthma in 7, by chronic cough in 3 and by laryngospasm in 2 cases. There was a correlation between the median area of BM and air PM10 levels during the week before FOB (p 2  vs 0,352 µm 2 , p=0,35).  In conclusion the median area of BM in AMs is correlated to air pollution exposure in children affected by CLADs, but it seems not to correlate to underlying diseases, age, sex and FEV1. A larger study group is necessary to better define the correlation of PM10 and CLADS in children.
BMA annual meeting: BMA condemns detention of children in police cells overnight
Authors: G. Iacobucci
Journal: BMJ (2015)

BMA leaders have urged the government to boost funding for child and adolescent mental health services across the country after lamenting the “unacceptable” overnight detention of children in police cells because of bed shortages.

The association’s annual representative meeting in Liverpool unanimously passed a motion that said, “This meeting . . . deplores the ongoing practice of …
Mutant Lines of Guinea Pig L 2 C Leukemia. II. Comparative Cytogenetic Studies and Banding Analyses of Normal and Leukemic Karyotypes
Authors: J. Whang Peng, E. C. Lee, G. Forni, I. Green
Journal: JNCI Journal of the National Cancer Institute (1976)

Chromosomes of normal guinea pig (strain 2) cells and of cell lines derived from a spontaneously arising leukemia were analyzed in detail. All cell lines studied, LG-L2C, GH-L2C, BZ-L*C, and EN-L2C, contained one M1 marker and two X chromosomes, in addition to other chromosome abnormalities specific for each cell line. The presence of the M1 marker and the two X chromosomes confirmed that all of these leukemic cell lines are derived from one ancestral line. Comparison of the chromosome markers and immunologic characteristics of these lines revealed that possibly the gene involved in the determination of C3 receptor sites is located on the terminal portion of the long arm of chromosome #2, but no other correlations could be made.
Synergism of Diethylstilbestrol and Other Carcinogens in Concurrent Development of Hepatic, Mammary, and Pituitary Tumors in Castrated Male Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C Sumi, K Yokoro, T Kajitani, A Ito
Journal: JNCI Journal of the National Cancer Institute (1980)

Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further treated with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues.
Responsibilities of Health Care Professionals in Counseling and Educating Patients With Incurable Neurological Diseases Regarding “Stem Cell Tourism”
Authors: Michelle Bowman, Michael Racke, John Kissel, Jaime Imitola
Journal: JAMA Neurology (2015)

"Stem cell tourism" is a rising Internet-based industry that aims to offer unproven procedures to patients with incurable diseases. This unregulated activity is reaching the neurologist's office as well as across the world, as patients request information or clearance for such procedures. Herein, we posit the need for medical societies and licensing boards to bring this issue to the forefront of neurology because it has the potential to affect patient care with risk of morbidity and mortality, as well as to undermine public confidence in legitimate stem cell research for incurable neurological diseases such as multiple sclerosis and amyotrophic lateral sclerosis.
Factors involved in deciding to start preventive treatment: qualitative study of clinicians' and lay people's attitudes
Authors: David K Lewis, Jude Robinson, Ewan Wilkinson
Journal: BMJ (2003)

Objectives To explore the views of clinicians and lay people about the minimum benefit needed to justify drug treatment to prevent heart attacks, and to explore the rationale behind treatment decisions. Design Qualitative study using semi-structured interviews. Participants 4 general practitioners, 4 practice nurses, and 18 lay people. Setting 8 general practices and 6 community settings across Liverpool. Results Participants varied widely in the minimum acceptable benefits chosen. Most people found the concepts difficult initially, and few appreciated that increased length of treatment should increase absolute benefits. Lay people usually wanted to make decisions for themselves, and clinicians supported this. Participants wanted to consider adverse effects and costs of treatment. Dislike of drug taking was common, and many people preferred lifestyle change to an imperfect treatment. Quality of life and personal views were more important than an individual's age. Conclusions Evidence based guidelines make assumptions about people's preferences, and, by using 10 year estimates of risk, inflate the apparent benefits of treatment. It is unlikely that guidelines could incorporate the wide range of people's preferences, and true dialogue is necessary between clinicians and patients before starting long term preventive treatment.
Acute changes in Atherogenic and Thrombogenic Factors with Cessation of Smoking
Authors: M D Feher, M W Rampling, J Brown, R Robinson, W Richmond, S Cholerton, B J Bain, P S Sever
Journal: Journal of the Royal Society of Medicine (1990)

Tobacco smoking is associated with alterations in several factors considered to be important in the atherosclerotic process. Thirty chronic smokers were studied 2 weeks before and 2 weeks after complete tobacco withdrawal. Significant reductions in fibrinogen, haematocrit, plasma viscosity and whole blood viscosity as well as a significant increase in HDL-cholesterol were observed. As these factors are important in both atherogenesis and thrombogenesis, these observations may give insight into tobacco-induced atherosclerotic disease and may be responsible for the more rapid reduction in the incidence of cardiovascular disease that is believed to occur after stopped smoking.
The effects of breathing manoeuvres on the trigeminocardiac reflex reversal of artificially induced supraventricular tachyarrhythmias into the sinus rhythm
Authors: Roman Benacka, Eva Sedlakova, Jan Sedlak
Journal: European Respiratory Journal (2011)

Trigeminocardiac reflexes (TCR) elicited from the intranasal, facial orbital, perinasal or forehead regions are known by a spectrum of respiratory and circulatory vegetative effects which are dominated by strong vagal reflex bradycardia that can be effectively used in the reversal of certain supraventricular tachyarrhythmias (SVTs). The present aim was to examine the effects of inspiratory (IA) and expiratory apneas (EA) (20-25s breath holding on TLC or FRC levels, respectively) and Valsalva manoeuvre (VM, 20s occl. pressure 35 mmHg) on the mechanism of reversal from SVTs by facial cold TCR (cold gel, 10°C for 60 s). AVNRT (15) and AVRT (2) (183±15 c min -1 ; M±SD) were induced by atrial electrical impulses (2-4mA, 1ms duration; 600 ms period) and/or by isoprenalin (1-5μg/min, i.v.) in 17 patients (18-62 y) while recording icECG, heart rate (HR) and blood pressure (BP). Data showed that TCR+EA and TCR+IA increased both bradycardic (26±3%, vs. 14±4%) as well as pressor effect (13±4% vs. 10±4%) of TCR. Moreover, TCR+IA and TCR+VM increased both the speed and success rate of SVTs reversal (by 11-15%, 45±2% vs. 33%). When applied alone IA, EA or VM decreased HR in SVTs (11,2±3,1%, n=19; 8,6±2,1%, n=9; 16,2±3,1 n=19, M±SD) and rised BP (6-19%). Occassionally, EA (18%) and IA (21%) reversed SVTs into the normal rhythm similar to TCR (27-45%) and VM (26%). The role of intrathoracic pressure changes and other reflex mechanisms underlying SVTs reversal by apnoeic manoeuvres and TCR are discussed.  Supported by the Agency of the Slovak Ministry of Education for the Structural Funds of the EU, under project ITMS: 26220120067; (30%)
Lower incidence of asthma exacerbations with FENO-guided anti-inflammatory treatment: A randomised controlled trial
Authors: Jörgen Syk, Andrei Malinovschi, Gunnar Johansson, Anna-Lena Undén, Kjell Alving
Journal: European Respiratory Journal (2012)

We examined the effects of anti-inflammatory treatment guided by fractional exhaled nitric oxide (FENO) on asthma outcomes in adult patients with allergic asthma.

This was a primary health care multicentre study (17 sites). 181 non-smoking participants (18-64 years) with perennial allergy and regular inhaled corticosteroid (ICS) treatment were randomly assigned to two treatment arms: a control group (n=88) where FENO was blinded for both patient and physician and the anti-inflammatory treatment (ICS and leukotriene receptor antagonists) adjusted according to routine clinical practice, and an active group (n=93) where the anti-inflammatory treatment was adjusted according to FENO. Participants were followed for one year (5 visits). FENO was measured and questionnaires on asthma-related quality of life (mini-AQLQ) and asthma control (6-item ACQ) were completed. Health care contacts and asthma events were noted at every visit.

The primary endpoint mini-AQLQ overall score over one year did not differ between the groups at last visit (p=0.20), whereas the mini-AQLQ symptom domain score (p=0.041) and the ACQ score (p=0.045) improved significantly more in the FENO-guided group than in the control group. Furthermore, a significantly lower cumulative incidence of exacerbations was found in the FENO-guided group vs. control group (p=0.029). This was dependent on a reduction in moderate (p=0.006) but not severe (p=0.73) exacerbations. Mean use of ICS over the study period was similar in the two groups (p=0.95).

Using FENO to guide anti-inflammatory treatment reduced exacerbation frequency and improved asthma control in adults with atopic asthma without increasing overall ICS use.
Electronic Interventions for Alcohol Misuse and Alcohol Use Disorders
Authors: Eric A. Dedert, Jennifer R. McDuffie, Roy Stein, J. Murray McNiel, Andrzej S. Kosinski, Caroline E. Freiermuth, Adam Hemminger, John W. Williams
Journal: Annals of Internal Medicine (2015)

The use of electronic interventions (e-interventions) may improve treatment of alcohol misuse.To characterize treatment intensity and systematically review the evidence for efficacy of e-interventions, relative to controls, for reducing alcohol consumption and alcohol-related impairment in adults and college students.MEDLINE (via PubMed) from January 2000 to March 2015 and the Cochrane Library, EMBASE, and PsycINFO from January 2000 to August 2014.English-language, randomized, controlled trials that involved at least 50 adults who misused alcohol; compared an e-intervention group with a control group; and reported outcomes at 6 months or longer.Two reviewers abstracted data and independently rated trial quality and strength of evidence.In 28 unique trials, the modal e-intervention was brief feedback on alcohol consumption. Available data suggested a small reduction in consumption (approximately 1 drink per week) in adults and college students at 6 months but not at 12 months. There was no statistically significant effect on meeting drinking limit guidelines in adults or on binge-drinking episodes or social consequences of alcohol in college students.E-interventions that ranged in intensity were combined in analyses. Quantitative results do not apply to short-term outcomes or alcohol use disorders.Evidence suggests that low-intensity e-inter ventions produce small reductions in alcohol consumption at 6 months, but there is little evidence for longer-term, clinically significant effects, such as meeting drinking limits. Future e-interventions could provide more intensive treatment and possibly human support to assist persons in meeting recommended drinking limits.U.S. Department of Veterans Affairs.
Neuronal Nitric Oxide Synthase Mediates Statin-Induced Restoration of Vasa Nervorum and Reversal of Diabetic Neuropathy
Authors: Masaaki Ii, Hiromi Nishimura, Kengo F. Kusano, Gangjian Qin, Young-sup Yoon, Andrea Wecker, Takayuki Asahara, Douglas W. Losordo
Journal: Circulation (2005)

Peripheral neuropathy is a frequent and major complication of diabetes.Severe peripheral neuropathy developed in type II diabetic mice, characterized by significant slowing of motor and sensory nerve conduction velocities. Rosuvastatin restored nerve vascularity, including vessel size, and nerve function also recovered to the levels of nondiabetic mice. Neuronal nitric oxide synthase expression in sciatic nerves was reduced in diabetic mice but was preserved by rosuvastatin. Coadministration of a nitric oxide synthase inhibitor with rosuvastatin attenuated the beneficial effects of rosuvastatin on nerve function and limited the recovery of vasa nervorum and nerve function. In vitro, rosuvastatin inhibited downregulation of neuronal nitric oxide synthase expression induced by high-glucose conditions in cultured Schwann cells. Furthermore, Akt phosphorylation in Schwann cells, downregulated by high-glucose conditions, was also restored by rosuvastatin, consistent with the change of neuronal nitric oxide synthase expression. Akt inhibition independently reduced neuronal nitric oxide synthase expression in Schwann cells in low-glucose cultures.These data indicate that the HMG-CoA reductase inhibitor rosuvastatin has a favorable effect on diabetic neuropathy independent of its cholesterol-lowering effect. Our data provide evidence that this effect may be mediated in part via neuronal nitric oxide synthase/nitric oxide and phosphatidylinositol 3-kinase/Akt-signaling pathways and also suggest that restoration or preservation of the microcirculation of the sciatic nerve may be involved.
Adding cisplatin (CDDP) to imatinib (IM) re-establishes tumor response following secondary resistance to IM in advanced chordoma
Authors: P. G. Casali, S. Stacchiotti, F. Grosso, A. Messina, F. Crippa, E. Tamborini, R. Bertieri, P. Collini, S. Pilotti, A. Gronchi
Journal: Journal of Clinical Oncology (2007)

10038 Background: IM is active in advanced chordoma, possibly by targeting PDGFRB. Secondary progressions following response have been observed. The case of a pt with sacral chordoma and lung adenocarcinoma responding to CDDP soon after stopping IM prompted us to combine the two drugs in IM-resistant advanced chordoma. Methods: Since February 2006, 6 advanced chordoma pts (F=4, M=2; mean age 56 yrs; PS 0–2) with a secondary resistance to IM following previous response, have started IM 400 mg/day + low-dose CDDP (25 mg/sqm/wk) on an individual use basis. Results: One pt completed her treatment (after 7 mos, reaching a total dose of CDDP = 525 mg/sqm), and, following ablation of the residual lesion, is now continuing on IM alone. The remaining pts are on combination therapy (4 for &lt;2 mos). After 4–6 weeks, 4 pts had a PET response (SUV max decrease ≥25%), with subjective improvement and stable disease on CT/MRI, while 2 were metabolically stable. In the 2 pts treated for &gt;12 weeks, a minor dimensional response was observed after 3 mos. The single pt who completed combination therapy had a continuous PET scan improvement throughout treatment, and pre-ablation biopsy of residual tumor showed histological signs of tumor response (marked cellular depletion and sclerohyalinosis in most of the sample, with residual tumor cells intermingled with inflammatory ones). Conclusions: In 4 out of 6 advanced chordoma pts progressing on IM, a tumor response was re-established by adding CDDP, and 2 pts treated for a relatively longer interval showed dimensional tumor shrinkage. Four more pts are starting therapy, and results will be updated. An independent cytotoxic effect of CDDP cannot be ruled out, but sensitivity of chordoma to CDDP is at best occasional. The combination of IM and CDDP may have synergic activity in chordoma. [Table: see text]
Studies on Acute Leukemia and Infectious Mononucleosis of Childhood. I. Viral Interference With Lymphoblastoid Cells of Spontaneously Transformed Bone Marrow Cultures&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Robert M. McCombs, Matilda Benyeshmelnick
Journal: JNCI Journal of the National Cancer Institute (1967)

Lymphoblastoid cells derived from spontaneously transformed bone marrow cultures of patients with leukemia or infectious mononucleosis were found to interfere with the plaque formation of vesicular stomatitis virus in a manner similar to that reported for the Burkitt lymphoma EB2 cells. The amount of interference mediated by these cells depended on the number of lymphoblastoid cells present in the culture and on the ability of the feeder monolayer to support their multiplication. The interference mechanism was shown to be due to the production by the lymphoblastoid cells of a virus inhibitor with the properties of interferon. The results obtained indicated that, in the presence of a substrate monolayer of human embryonic-bone marrow or spleen fibroblasts, the interference phenomenon was not specific for the lymphoblastoid or EB2 cells. Under these conditions, peripheral blood leukocytes from either normal individuals or patients with leukemia were as efficient, both in their interference capability and in their interferon production, as were the lymphoblastoid cells. The chief difference detected between the cells was that the lymphoblastoid cells produced interferon spontaneously in the absence of substrate monolayer, whereas peripherall blood leukocytes did not. In this respect, however, there was no difference between normal and leukemic peripheral blood leukocytes.
Introduction of Thomas E. Andreoli
Authors: R R Robinson
Journal: Journal of the American Society of Nephrology (1996)

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