Successful treatment of desmoid tumor of the chest wall with tranilast: a case report

<p>Abstract</p> <p>Introduction</p> <p>Desmoid tumor is characterized by infiltrative growth and local recurrence often occurs after surgery. To reduce the local recurrence rate, adjuvant therapy, such as radiotherapy and pharmacotherapy with cytotoxic agents, anti-estrogen agents and non-steroidal anti-inflammatory drugs, is often applied. In addition, these non-surgical treatments are also performed in patients with unresectable desmoid tumors. We successfully treated a patient with a desmoid tumor with tranilast; an anti-allergic agent.</p> <p>Case presentation</p> <p>A 48-year-old Japanese man with a slow-growing desmoid tumor on his chest wall was treated with an oral administration of tranilast (300 mg per day, three times a day). Two years and two months after the commencement of his therapy, the tumor became impalpable. At this time, the oral administration of tranilast was discontinued. Two years after discontinuation of the treatment, a physical examination showed no recurrence of the tumor and he continued in a state of remission. We were successfully able to reduce the size of the tumor and thereafter maintain the reduced size.</p> <p>Conclusion</p> <p>Tranilast was clinically effective in our case, and is probably comparable to cytotoxic agents or anti-estrogen agents. Because tranilast has substantially fewer adverse effects than cytotoxic agents, it could be a very useful therapeutic agent for desmoid tumor.</p

The Tell-Tale Heart: Population-Based Surveillance Reveals an Association of Rofecoxib and Celecoxib with Myocardial Infarction

Background. COX-2 selective inhibitors are associated with myocardial infarction (MI). We sought to determine whether population health monitoring would have revealed the effect of COX-2 inhibitors on population-level patterns of MI. Methodology/Principal Findings. We conducted a retrospective study of inpatients at two Boston hospitals, from January 1997 to March 2006. There was a population-level rise in the rate of MI that reached 52.0 MI-related hospitalizations per 100,000 (a two standard deviation exceedence) in January of 2000, eight months after the introduction of rofecoxib and one year after celecoxib. The exceedence vanished within one month of the withdrawal of rofecoxib. Trends in inpatient stay due to MI were tightly coupled to the rise and fall of prescriptions of COX-2 inhibitors, with an 18.5 % increase in inpatient stays for MI when both rofecoxib and celecoxib were on the market (P,0.001). For every million prescriptions of rofecoxib and celecoxib, there was a 0.5 % increase in MI (95%CI 0.1 to 0.9) explaining 50.3 % of the deviance in yearly variation of MI-related hospitalizations. There was a negative association between mean age at MI and volume of prescriptions for celecoxib and rofecoxib (Spearman correlation, 20.67, P,0.05). Conclusions/Significance. The strong relationship between prescribing and outcome time series supports a population-level impact of COX-2 inhibitors on MI incidence. Further, mean age at MI appears to have been lowered by use of these medications. Use of a population monitoring approach as an adjunct t

Digital orphans: Data closure and openness in patient- powered networks

This is the author accepted manuscript. The final version is available from Palgrave Macmillan via the DOI in this record.In this paper, we discuss an issue linked to data-sharing regimes in patient-powered, social-media-based networks, namely that most of the data that patient users share are not used to research scientific issues or the patient voice. This is not a trivial issue, as participation in these networks is linked to openness in data sharing, which would benefits fellow patients and contributes to the public good more generally. Patient-powered research networks are often framed as disrupting research agendas and the industry. However, when data that patients share are not accessible for research, their epistemic potential is denied. The problem is linked to the business models of the organisations managing these networks: models centred on controlling patient data tend to close networks with regard to data use. The constraint on research is at odds with the ideals of a sharing, open and supportive epistemic community that networks’ own narratives evoke. This kind of failure can create peculiar scenarios, such as the emergence of the ‘digital orphans’ of Internet research. By pointing out the issue of data use, this paper informs the discussion about the capacity of patient-powered networks to support research participation and the patient voice.We are indebted to the anonymous reviewers and the editor, who with their supportive and constructive comments helped us to better clarify and highlight the argument of the article. We would like to also thank friends and colleagues who have offered valuable comments and suggestions on early drafts of this paper. We would like to especially thank Barbara Prainsack, Sabina Leonelli, Alena Buyx, and David Teira. This research is funded by the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement number 335925, and the German Federal Ministry of Education and Research (grant number 01GP1311

A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents for colorectal neoplasia. Polymorphisms in NSAID targets or metabolizing enzymes may affect NSAID efficacy or toxicity. We conducted a literature review to summarize current evidence of gene-drug interactions between NSAID use and polymorphisms in COX1, COX2, ODC, UGT1A6 and CYP2C9 on risk of colorectal neoplasia by searching OVID and PubMed. Of 134 relevant search results, thirteen investigated an interaction. One study reported a significant interaction between NSAID use and the COX1 Pro17Leu polymorphism (P=0.03) whereby the risk reduction associated with NSAID use among homozygous wild-type genotypes was not observed among NSAID users with variant alleles. Recent pharmacodynamic data support the potential for gene-drug interactions for COX1 Pro17Leu. Statistically significant interactions have also been reported for ODC (315G>A), UGT1A6 (Thr181Ala+Arg184Ser or Arg184Ser alone), and CYP2C9 (*2/*3). No statistically significant interactions have been reported for polymorphisms in COX2; however, an interaction with COX2 -765G>C approached significance (P=0.07) in one study. Among seven remaining studies, reported interactions were not statistically significant for COX1, COX2 and ODC gene polymorphisms. Most studies were of limited sample size. Definitions of NSAID use differed substantially between studies. The literature on NSAID-gene interactions to date is limited. Reliable detection of gene-NSAID interactions will require greater sample sizes, consistent definitions of NSAID use and evaluation of clinical trial subjects of chemoprevention studies

Reporting bias in medical research - a narrative review

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles

Why we need easy access to all data from all clinical trials and how to accomplish it

International calls for registering all trials involving humans and for sharing the results, and sometimes also the raw data and the trial protocols, have increased in recent years. Such calls have come, for example, from the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO), the US National Institutes of Heath, the US Congress, the European Commission, the European ombudsman, journal editors, The Cochrane Collaboration, and several funders, for example the UK Medical Research Council, the Wellcome Trust, the Bill and Melinda Gates Foundation and the Hewlett Foundation

Myocardial ischemia and reperfusion: The role of oxygen radicals in tissue injury

Thrombolytic therapy has gained widespread acceplance as a means of treating coronary artery thrombosis in patients with acute myocardial infarction. Although experimental data have demonstrated that timely reperfusion limits the extent of infarction caused by regional ischemia, there is growing evidence that reperfusion is associated with an inflammatory response to ischemia that exacerbates the tissue injury. Ischemic myocardium releases archidonate and complement-derived chemotactic factors, e.g., leukotriene B 4 and C 5a , which attract and activate neutrophils. Reperfusion of ischemic myocardium accelerates the influx of neutrophils, which release reactive oxygen products, such as superoxide anion and hydrogen peroxide, resulting in the formation of a hydroxyl radical and hypochlorous acid. The latter two species may damage viable endothelial cells and myocytes via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Neutrophil depletion by antiserum and inhibition of neutrophil function by drugs, e.g., ibuprofen, prostaglandins (prostacyclin and PGE 1 ), or a monoclonal antibody, to the adherence-promoting glycoprotein Mo-1 receptor, have been shown to limit the extent of canine myocardial injury due to coronary artery occlusion/reperfusion. Recent studies have challenged the hypothesis that xanthine-oxidase-derived oxygen radicals are a cause of reperfusion injury. Treatment with allopurinol or oxypurinol may exert beneficial effects on ischemic myocardium that are unrelated to the inhibition of xanthine oxidase. Furthermore, the human heart may lack xanthine oxidase activity. Further basic research is needed, therefore, to clarify the importance of xanthine oxidase in the pathophysiology of reperfusion injury. Current data are highly suggestive of a deleterious role of the neutrophil in organ reperfusion and justify consideration of the clinical investigation of neutrophil inhibitors in patients receiving thrombolytic agents during the evolution of an acute myocardial infarction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44595/1/10557_2004_Article_BF00133206.pd

Interleukin-1 beta has atheroprotective effects in advanced atherosclerotic lesions of mice

Despite decades of research, our understanding of the processes controlling late-stage atherosclerotic plaque stability remains poor. A prevailing hypothesis is that reducing inflammation may improve advanced plaque stability, as recently tested in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, in which post-myocardial infarction subjects were treated with an IL-1β antibody. Here, we performed intervention studies in which smooth muscle cell (SMC) lineage-tracing Apoe-/- mice with advanced atherosclerosis were treated with anti-IL-1β or IgG control antibodies. Surprisingly, we found that IL-1β antibody treatment between 18 and 26 weeks of Western diet feeding induced a marked reduction in SMC and collagen content, but increased macrophage numbers in the fibrous cap. Moreover, although IL-1β antibody treatment had no effect on lesion size, it completely inhibited beneficial outward remodeling. We also found that SMC-specific knockout of Il1r1 (encoding IL-1 receptor type 1) resulted in smaller lesions nearly devoid of SMCs and lacking a fibrous cap, whereas macrophage-selective loss of IL-1R1 had no effect on lesion size or composition. Taken together, these results show that IL-1β has multiple beneficial effects in late-stage murine atherosclerosis, including promotion of outward remodeling and formation and maintenance of an SMC- and collagen-rich fibrous cap