tbuckley/cabot-search huggingface dataset:
Consultation on basic asthma research strategy
Authors: T.H. Lee
Journal: European Respiratory Journal (2002)

There have been major advances in the understanding of the mechanisms and genetics of asthma in recent years.Some findings have already led to the development of new therapeutic agents, and others may be the basis for further new drug entities.However, while much has been achieved, many challenges remain.Prevalence of the condition continues to grow, and in the UK, an estimated 8 million people are diagnosed as having asthma, with 5 million people receiving treatment.The cost of asthma to the National Health Service in the UK is w£850 million (yJ1,360 million) a year [1].In the light of the recent rapid expansion of knowledge, the National Asthma Campaign in the UK decided to gain a consensus on the priorities for asthma research over the next 5 yrs.The executive summary was published in Clinical Experimental Allergy [2] and the full document [3], which encompasses consensus views on current research and recommendations for future work, is available from the Research Director, National Asthma Campaign, Providence House, Providence
Global strategy for asthma management and prevention: GINA executive summary
Authors: E. D. Bateman, S. S. Hurd, P. J. Barnes, J. Bousquet, J. M. Drazen, M. FitzGerald, P. Gibson, K. Ohta, P. O'Byrne, S. E. Pedersen, E. Pizzichini, S. D. Sullivan, S. E. Wenzel, H. J. Zar
Journal: European Respiratory Journal (2007)

Asthma is a serious health problem throughout the world. During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively. However, recommendations for asthma care need to be adapted to local conditions, resources and services. Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations. A comprehensive workshop report entitled "A Global Strategy for Asthma Management and Prevention", first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines. The 2006 report contains important new themes. First, it asserts that "it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained," and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions. The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised.
A role for NF-κB–dependent gene transactivation in sunburn
Authors: Kazuhiro Abeyama, William Eng, James V. Jester, Arie A. Vink, Dale Edelbaum, Clay J. Cockerell, Paul R. Bergstresser, Akira Takashima
Journal: Journal of Clinical Investigation (2000)

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB–dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-κB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-κB target genes, rather than from nonspecific changes associated with tissue damage.
Physicians' Attitudes Toward Using Deception
Authors: Robert Baker
Journal: JAMA (1989)

In the article entitled "Physicians' Attitudes Toward Using Deception to Resolve Difficult Ethical Problems," Novack et al<sup>1</sup>raise more questions about methodology than about morality. The study is predicated on scenarios, half of which are analyzed in terms of the notion of "passive deception," ie, "nondisclosure, [or] allowing another to deceive, or failing to correct a misconception." This definition is standard neither in the philosophical literature nor in ordinary usage, and has the curious effect of making deception a transitive concept, ie, anyone who allows or agrees to deception can be said to be deceivers themselves. Thus, in one scenario, the authors claim that physicians who merely "agree" to allowing a husband's deception of his wife are themselves "deceivers." In a second scenario, a version of the Robert John Denis Browne case,<sup>2,3</sup>the authors characterize as (passive) deceivers physicians who decline to divulge to the mother of a
Survivorship Care Plans: A Change of Perspective or a Failure
Authors: Ernesto Zanet, Mariagrazia Michieli, Umberto Tirelli
Journal: Journal of Clinical Oncology (2014)

stress that oncologists responding to their surveyrarelyreleasewrittenreportsorindicationsaboutcancersurvivorprovid-ers.Thisbehaviorismorepronouncedamongprimarycarephysicians(PCPs). This is not surprising, because cancer survivors are only aminorityofthepatientsseenineverydaybyPCPs,whooftenlackthenecessaryexperienceandskillstocoordinatetheirfollow-upappoint-ments. In addition, the authors
PSYCHIATRIST-SOCIAL WORKER INTERRELATIONSHIP
Authors: MARIANNE HORNEY
Journal: American Journal of Psychiatry (1942)

This paper deals with the attitudes that the psychiatric and social work professions have towards each other. One notices an attempt on the part of the social workers to avoid the criticism of the psychiatrists by formulating an artificial distinction between the two overlapping fields. The social worker's position is made difficult by her being drawn into divergencies of schools of thought within the psychiatric profession. The main practical point arising out of this interrelationship is the need to define cases that could be carried by social workers by the therapeutic need and approachability rather than by the degree of sickness. Difficulties relating to the management of psychiatric problems arising in case work approach are touched upon.
Abstract 3584: Effects of the investigational selective MEK inhibitor TAK-733 against cutaneous and uveal melanoma cell lines
Authors: Erika von Euw, Mohammad Atefi, Narsis Attar, Sybil Zachariah, Barry L. Burgess, Tara McCannel, David I. Lichter, Elena Izmailova, Antoni Ribas
Journal: Cancer Research (2011)

Abstract Background. There are several MEK inhibitors currently under clinical investigation, including, TAK-733, a novel non-ATP-competitive allosteric selective inhibitor of MEK. We have analyzed the sensitivity of human melanoma cell lines of different origins to TAK-733. Methods. The half maximal inhibitory concentration (IC50) of TAK-733 was assessed in a panel of 27 skin melanoma cell lines and 5 ocular melanoma cell lines genotyped for driver and secondary oncogenic mutations. Flow cytometry was used to analyze effects on cell cycle progression, and Western blots to analyze the downstream signaling changes upon exposure to TAK-733. Results. Among 12 BRAFV600E mutated cell lines tested, 6 were sensitive to TAK-733 with IC50s less than 10 nM, including 4 highly sensitive cell lines with IC50s below 1 nM. In 5 cell lines with BRAFV600E mutation the IC50 was higher than 100 nM and were considered highly resistant. Among 10 NRASQ61L mutant melanoma cell lines, 6 were sensitive with IC50s below 10 nM. Among 5 melanoma cell lines with wild type sequences for NRAS, BRAF, GNAQ and GNA11 genes only 1 was sensitive to TAK-733. All 5 of the uveal melanoma cell lines were highly sensitive to TAK-733 IC50 regardless of having a GNAQ or GNA11 mutations. MEK inhibition resulted in increase of pMEK more prominently in NRASQ61L mutant and GNAQ mutant cell lines than in BRAFV600E mutant cell lines. In all cases TAK-733 induced marked dose-dependent inhibition of pERK, regardless of the driver oncogenic mutation or the sensitivity or resistance to this agent in cell viability assays. Cell lines resistant to TAK-733 showed no inhibition of pAKT or pS6K, while there was a general trend towards inhibition of these two phosphorylated molecules in sensitive cell lines. Conclusions. TAK-733 is a potent MEK inhibitor with high antitumor activity against human melanoma cell lines with BRAF, NRAS, GNAQ and GNA11 driver mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3584. doi:10.1158/1538-7445.AM2011-3584
Chronic lymphocytic gastritis and protein losing gastropathy.
Authors: J R Crampton, J O Hunter, G Neale, D G Wight
Journal: Gut (1989)

<h3>Objective</h3> Dural arteriovenous fistulae (dAVF) are rare vascular lesions of the CNS with potentially significant morbidity and mortality. Our experience in the treatment of children with dAVF is reported. <h3>Design</h3> Our neurosurgical and neurointerventional pediatric database was retrospectively reviewed for patients with dAVF. Brain arteriovenous malformations, pial fistulae, vein of Galen malformations and extracranial fistulae were excluded. Angiography was used to assess radiographic outcome in all cases. Clinical outcome was assessed by the pediatric Functional Status Scale (6=normal, maximal incapacity=30). <h3>Results</h3> Between July 2003 and June 2011, seven patients with dAVF were treated, with a mean age at presentation of 4.8 years. Presenting symptoms included facial venous prominence, headache, macrocephaly and symptoms of elevated intracranial pressure; one patient (14%) had asymptomatic dAVF discovered on imaging follow-up after craniotomy for cavernous malformation. Two cases (28%) were associated with vascular anomaly syndromes, PHACE association and PTEN associated syndrome. Venous sinus thrombosis was identified in four patients (57%) and was associated with a systemic hypercoagulable state or trauma. Complete obliteration was achieved in six of seven patients. Treatment was exclusively endovascular in six patients and by combined surgical/endovascular means in the remaining patient. No treatment complications were experienced. Functional Status Scale scores at an average of 2 years of follow-up were 6 in all patients. <h3>Conclusion</h3> Treatment is effective in the obliteration of dAVF in children and is well tolerated, with patients having excellent prognoses. Genetic screening and hypercoagulable workup are indicated, particularly when other anomalies or sinus thrombosis coexist.
Three-Year Outcomes After Sirolimus-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Disease
Authors: Mamoru Toyofuku, Takeshi Kimura, Takeshi Morimoto, Yasuhiko Hayashi, Hiroaki Ueda, Kazuya Kawai, Yoichi Nozaki, Shinichi Hiramatsu, Akira Miura, Yoshiaki Yokoi, Shinichiro Toyoshima, Hitoshi Nakashima, Kazuo Haze, Masaru Tanaka, Shunsuke Take, Shigeru Saito, Takaaki Isshiki, Kazuaki Mitsudo
Journal: Circulation (2009)

Long-term outcomes after stenting of an unprotected left main coronary artery (ULMCA) with drug-eluting stents have not been addressed adequately despite the growing popularity of this procedure.j-Cypher is a multicenter prospective registry of consecutive patients undergoing sirolimus-eluting stent implantation in Japan. Among 12 824 patients enrolled in the j-Cypher registry, the unadjusted mortality rate at 3 years was significantly higher in patients with ULMCA stenting (n=582) than in patients without ULMCA stenting (n=12 242; 14.6% versus 9.2%, respectively; P<0.0001); however, there was no significant difference between the 2 groups in the adjusted risk of death (hazard ratio 1.23, 95% confidence interval 0.95 to 1.60, P=0.12). Among 476 patients whose ULMCA lesions were treated exclusively with a sirolimus-eluting stent, patients with ostial/shaft lesions (n=96) compared with those with bifurcation lesions (n=380) had a significantly lower rate of target-lesion revascularization for the ULMCA lesions (3.6% versus 17.1%, P=0.005), with similar cardiac death rates at 3 years (9.8% versus 7.6%, P=0.41). Among patients with bifurcation lesions, patients with stenting of both the main and side branches (n=119) had significantly higher rates of cardiac death (12.2% versus 5.5%; P=0.02) and target-lesion revascularization (30.9% versus 11.1%; P<0.0001) than those with main-branch stenting alone (n=261).The higher unadjusted mortality rate of patients undergoing ULMCA stenting with a sirolimus-eluting stent did not appear to be related to ULMCA treatment itself but rather to the patients' high-risk profile. Although long-term outcomes in patients with ostial/shaft ULMCA lesions were favorable, outcomes in patients with bifurcation lesions treated with stenting of both the main and side branches appeared unacceptable.
Comments on Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines
Authors: Sheldon Spector, Dana Wallace, Richard Nicklas, Jay Portnoy, Joann Blessing-Moore, David Bernstein, Linda Cox, John Oppenheimer, David Lang, Diane Schuller, Christopher Randolph, Stephen Tilles, David Khan
Journal: Journal of Allergy and Clinical Immunology (2011)
Use of the Tetracycline System for Inducible Protein Synthesis in the Kidney
Authors: Anna Rachel Gallagher, Kai Schönig, Nelson Brown, Hermann Bujard, Ralph Witzgall
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The great advantage of the tetracycline-inducible system lies in its ability to address a large variety of biological questions in a time-dependent and tissue-specific manner. This study describes a transgenic mouse line, rTALAP-1, which produces the reverse tetracycline transactivator under control of the liver activator protein (LAP) promoter. Two reporter lines with luciferase and LacZ reporter genes were used to demonstrate predominant expression in the kidney and liver when doxycycline was added to the drinking water. In the kidney, transgene expression was found primarily in cortical proximal tubules. No luciferase and β-galactosidase activity was detected in mice without doxycycline in the drinking water, which attests to the tight control of this system. One of the advantages of the tet system lies in its reversibility, and indeed, a virtually complete remission of transgene activity in both the kidney and liver was observed when doxycycline was withdrawn. Also examined was transactivator activity during development by exposing the mothers producing the reverse transactivator to doxycycline before mating. Transgene activity was detected in newborn kidneys and liver, indicating that sufficient amounts of doxycycline had crossed the placental barrier. During nephron development, the LAP promoter appeared to be only active in the more mature proximal tubules. Finally, the rTALAP-1 line was used to inducibly express the human PKD2 cDNA in proximal tubules of transgenic mice, but no cystic changes were detected, even after 6 mo of induction. E-mail: [email protected]
Improving Cancer Outcomes Through International Collaboration in Academic Cancer Treatment Trials
Authors: Edward L. Trimble, Jeffrey S. Abrams, Ralph M. Meyer, Fabien Calvo, Eduardo Cazap, James Deye, Elizabeth Eisenhauer, Thomas J. Fitzgerald, Denis Lacombe, Max Parmar, Nita Seibel, Lalitha Shankar, Ann Marie Swart, Patrick Therasse, Bhadrasain Vikram, Remy von Frenckell, Michael Friedlander, Keiichi Fujiwara, Richard S. Kaplan, Francoise Meunier
Journal: Journal of Clinical Oncology (2009)

Purpose The need for international collaboration in cancer clinical trials has grown stronger as we have made progress both in cancer treatment and screening. We sought to identify those efforts already underway which facilitate such collaboration, as well as barriers to greater collaboration. Methods We reviewed the collective experiences of many cooperative groups, governmental organizations, nongovernmental organizations, and academic investigators in their work to build international collaboration in cancer clinical trials across multiple disease sites. Results More than a decade of work has led to effective global harmonization for many of the elements critical to cancer clinical trials. Many barriers remain, but effective international collaboration in academic cancer treatment trials should become the norm, rather than the exception. Conclusion Our ability to strengthen international collaborations will result in maximization of our resources and patients, permitting us to change practice by establishing more effective therapeutic strategies. Regulatory, logistical, and financial hurdles, however, often hamper the conduct of joint trials. We must work together as a global community to overcome these barriers so that we may continue to improve cancer treatment for patients around the world.
Faecal ammonia and pH during lactulose administration in man: comparison with other cathartics
Authors: L. Agostini, P. F. Down, J. Murison, O. M. Wrong
Journal: Gut (1972)

The effect of lactulose on faecal pH and ammonia has been studied in three normal subjects with the aid of dialysis of faeces in vivo. Observations were also made with sodium sulphate and the two hexahydric alcohols, mannitol and sorbitol, given in doses sufficient to cause a similar increase in stool weight. All four cathartics rendered the stool more acid, but there was no increase in the concentration of faecal ammonia. Lactulose, despite increasing faecal volume, did not cause an increase in the absolute amount of ammonia lost in the faeces, but the other purgatives did show a modest rise. The results are inconsistent with the theory that lactulose benefits the clinical picture of portosystemic encephalopathy by trapping ammonia in an acid stool. An alternative suggestion is advanced, namely, that any cathartic (including lactulose) reduces ammonia absorption from the colon by decreasing colonic transit time, and so reducing the amount of ammonia generated by autolysis of colonic bacteria.
Genetic and teratogenic effects of cancer treatments on gametes and embryos
Authors: J. Arnon, D. Meirow, H. Lewis-Roness, A. Ornoy
Journal: Human Reproduction Update (2001)

Male and female germ cells vary in their sensitivity to the mutagenic effects of chemotherapy and radiotherapy, depending on their stage of maturation and the agent used. Although sperm DNA damage exists following treatment, no increase in genetic defects or congenital malformations was detected among children conceived to parents who have previously undergone chemotherapy or radiotherapy. The use of assisted reproductive technologies and micromanipulation techniques might increase this risk; hence caution should be exercised. In female cancer patients, miscarriage and congenital malformations are not increased following chemotherapy. However, when IVF and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence the babies should be screened. During pregnancy, the potential teratogenic effects of chemotherapy influence the choice and timing of therapy. Termination is usually recommended in the first trimester. Second- and third-trimester exposure does not usually increase the teratogenic risk and cognitive development, but it may increase the risk of poor obstetric outcome and fetal myelosuppression. During the first two weeks after fertilization of the embryo, radiation is lethal but not teratogenic. High doses of radiation during pregnancy induce anomalies, impaired growth and mental retardation, and there may be an increased risk of childhood leukaemia and other tumours in the offspring.
Mortality Risk Among Offspring of Psychiatric Inpatients: A Population-Based Follow-Up to Early Adulthood
Authors: Roger Webb
Journal: American Journal of Psychiatry (2006)

The purpose of this article was to estimate relative risks of all-cause mortality associated with parental psychiatric disorder based on offspring age (up to 25 years of age), parental diagnosis, maternal versus paternal disorder, and number of affected parents.The study group consisted of all Danish singleton live and stillbirths (N=1.46 million) during 1973-1998, identified using the Central Population Register and Medical Birth Register. Dates of death were recorded with follow-up to Jan. 1, 1999. Parental admission histories since 1969 were obtained from the Psychiatric Central Register.Mortality risks were elevated from birth through early adulthood among offspring of people admitted with any type of psychopathology, although relative risks were attenuated during school attendance years. Effect sizes varied according to offspring ages, the highest being during infancy. The following high-risk subgroups were identified: postneonates with two mentally ill parents, neonates and postneonates whose mothers had alcohol and drug-related disorders, and neonates whose mothers had affective disorders. In general, from the postneonatal period onward, there was no indication that maternal psychopathology is associated with higher offspring mortality risk than paternal disorder.The greatest number of excess deaths were attributable to alcohol-related disorders, this being the most prevalent paternal diagnostic category and the second most prevalent in mothers. Some findings were unexpected. For example, there was no evidence that mortality risk among offspring of parents with schizophrenia and related disorders was significantly greater than that associated with all other parental psychiatric conditions, whereas the relative risk for neonatal death associated with maternal affective disorders was markedly raised.