122 research outputs found

    Experimental assessment of pro-lymphangiogenic growth factors in the treatment of post-surgical lymphedema following lymphadenectomy

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    Introduction: Lymphedema is a frequent consequence of lymph node excision during breast cancer surgery. Current treatment options are limited mainly to external compression therapies to limit edema development. We investigated previously, postsurgical lymphedema in a sheep model following the removal of a single lymph node and determined that autologous lymph node transplantation has the potential to reduce or prevent edema development. In this report, we examine the potential of lymphangiogenic therapy to restore lymphatic function and reduce postsurgical lymphedema. Methods: Lymphangiogenic growth factors (vascular endothelial growth factor C (VEGF-C)) and angiopoietin-2 (ANG-2) were loaded into a gel-based drug delivery system (HAMC; a blend of hyaluronan and methylcellulose). Drug release rates and lymphangiogenic signaling in target endothelial cells were assessed in vitro and vascular permeability biocompatibility tests were examined in vivo. Following, the removal of a single popliteal lymph node, HAMC with the growth factors was injected into the excision site. Six weeks later, lymphatic functionality was assessed by injecting 125Iodine radiolabeled bovine serum albumin (125I-BSA) into prenodal vessels and measuring its recovery in plasma. Circumferential leg measurements were plotted over time and areas under the curves used to quantify edema formation. Results: The growth factors were released over a two-week period in vitro by diffusion from HAMC, with 50% being released in the first 24 hr. The system induced lymphangiogenic signaling in target endothelial cells, while inducing only a minimal inflammatory response in sheep. Removal of the node significantly reduced lymphatic functionality (nodectomy 1.9 ± 0.9, HAMC alone 1.7 ± 0.8) compared with intact groups (3.2 ± 0.7). In contrast, there was no significant difference between the growth factor treatment group (2.3 ± 0.73) and the intact group indicating improved function with the molecular factors. An increase in the number of regenerated lymphatic vessels at treatment sites was observed with fluoroscopy. Groups receiving HAMC plus growth factors displayed significantly reduced edema (107.4 ± 51.3) compared with nontreated groups (nodectomy 219.8 ± 118.7 and HAMC alone 162.6 ± 141). Conclusions: Growth factor therapy has the potential to increase lymphatic function and reduce edema magnitude in an animal model of lymphedema. The application of this concept to lymphedema patients warrants further examination

    A philosophical analysis of the evidence-based medicine debate

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    BACKGROUND: The term "evidence-based medicine" (or EBM) was introduced about ten years ago, and there has been considerable debate about the value of EBM. However, this debate has sometimes been obscured by a lack of conceptual clarity concerning the nature and status of EBM. DISCUSSION: First, we note that EBM proponents have obscured the current debate by defining EBM in an overly broad, indeed almost vacuous, manner; we offer a clearer account of EBM and its relation to the alternative approaches to medicine. Second, while EBM proponents commonly cite the philosophical work of Thomas Kuhn and claim that EBM is a Kuhnian 'paradigm shift,' we argue that such claims are seriously mistaken and unduly polarize the EBM debate. Third, we suggest that it is much more fruitful to understand the relationship between EBM and its alternatives in light of a different philosophical metaphor: W.V. Quine's metaphor of the web of belief. Seen in this way, we argue that EBM is an approach to medical practice that is indeed importantly different from the alternatives. SUMMARY: We can have a more productive debate about the value of EBM by being clearer about the nature of EBM and its relationship to alternative approaches to medicine

    Fluoro-deoxi-glucose uptake and angiogenesis are independent biological features in lung metastases

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    Neoangiogenesis and enhanced glucose metabolism in neoplasms are likely to be activated by the same biochemical stimulus; hypoxia. A correlation between these two parameters has been postulated. The objective of this study was to evaluate the relationship between Fluoro-desoxi-glucose uptake at positron emission tomography scan and angiogenesis in lung metastasis. Fluoro-desoxi-glucose activity, expressed as a standard uptake value, and microvessel intratumoural density, were retrospectively calculated in a series of 43 lung metastasis resected in 19 patients. Primary sites were colorectal cancer in 16 metastases, sarcoma in eight, gynaecological in four and other sites in 15. The correlation between the two parameters was tested by logistic regression and multivariate analysis. Positron emission tomography scan was positive in 17 patients (sensitivity 89%). No correlation was observed between standard uptake value and microvessel intratumoural density in this series of lung metastasis. Positron emission tomography negative and positive nodules presented comparable value of microvessel intratumoural density (12.9 vs 11.3). Standard uptake value was significantly correlated with nodules size and was higher in colon cancer metastasis than in sarcoma ones. Microvessel intratumoural density was independent from nodule size but significantly higher in sarcoma than in colon cancer metastasis. The lack of correlation was confirmed by multivariate analysis after adjustment for tumour type and nodules size. The present study demonstrated that positron emission tomography scan is positive in a high proportion of patients regardless of microvessel density. Glucose uptake and angiogenesis appear to be independent biological features in lung metastasis. This observation may have implications for future antiangiogenic therapies

    Clinical evaluation of marketed orthodontic products: are researchers behind the times? A meta-epidemiological study.

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    BACKGROUND: The role of marketing and industry in the treatment decisions of orthodontists has received increasing attention in recent years with clinical research typically undertaken subsequent to established use of these devices and often failing to confirm the promise of manufacturers' claims. This meta-epidemiological study was undertaken to assess the proportion of clinical trials in orthodontics evaluating commercially marketed products and to evaluate the direction of the results of these studies. METHODS: Electronic searching was undertaken to identify randomized controlled trials (RCTs) published over a 5-year period (1 January 2012 to 31 December 2016). Data obtained included the type of marketed intervention, direction of effect and declaration of both industry sponsorship and conflict of interest. RESULTS: Eighty-four RCTs published in 23 scientific journals were included with the highest percentage in the American Journal of Dentofacial Orthopedics (AJO-DO) (23.8%), followed by the European Journal of Orthodontics (EJO) (14.3%), Journal of Orthodontics (JO) (10.7%) and Angle Orthodontist (AO) (10.7%). Overall, 45% (38/84) of clinical trials assessed involved analysis of marketed products after their introduction. Interventions to improve oral health or circumvent the risk of iatrogenic damage, such as white spot lesions, were most commonly assessed (15.8%), with the relative merits of non-surgical adjuncts (14.1%) and other orthodontic auxiliaries (13.1%) also frequently evaluated. In 44% of RCTs, a positive effect of the marketed intervention was not reported. Industry sponsorship of the research was declared in 9.5% RCTs. No significant associations between the direction of the effect and both declaration of industry sponsorship (p = 0.56) and conflict of interest (p = 0.96) were detected. Moreover, for marketed and non-marketed products, no significant associations for both declaration of industry sponsorship (p = 0.44) and conflict of interest (p = 0.28) were found. CONCLUSIONS: Almost half of orthodontic clinical trials over the past 5 years involve analysis of marketed products after their introduction. The results highlight a potential source of waste in orthodontic research emanating from existing approaches to licensing and marketing of orthodontic products

    Protein-based identification of quantitative trait loci associated with malignant transformation in two HER2+ cellular models of breast cancer

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    Background A contemporary view of the cancer genome reveals extensive rearrangement compared to normal cells. Yet how these genetic alterations translate into specific proteomic changes that underpin acquiring the hallmarks of cancer remains unresolved. The objectives of this study were to quantify alterations in protein expression in two HER2+ cellular models of breast cancer and to infer differentially regulated signaling pathways in these models associated with the hallmarks of cancer. Results A proteomic workflow was used to identify proteins in two HER2 positive tumorigenic cell lines (BT474 and SKBR3) that were differentially expressed relative to a normal human mammary epithelial cell line (184A1). A total of 64 (BT474-184A1) and 69 (SKBR3-184A1) proteins were uniquely identified that were differentially expressed by at least 1.5-fold. Pathway inference tools were used to interpret these proteins in terms of functionally enriched pathways in the tumor cell lines. We observed protein ubiquitination and apoptosis signaling pathways were both enriched in the two breast cancer models while IGF signaling and cell motility pathways were enriched in BT474 and amino acid metabolism were enriched in the SKBR3 cell line. Conclusion While protein ubiquitination and apoptosis signaling pathways were common to both the cell lines, the observed patterns of protein expression suggest that the evasion of apoptosis in each tumorigenic cell line occurs via different mechanisms. Evidently, apoptosis is regulated in BT474 via down regulation of Bid and in SKBR3 via up regulation of Calpain-11 as compared to 184A1

    Tumour-associated carbohydrate antigens in breast cancer

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    Glycosylation changes that occur in cancer often lead to the expression of tumour-associated carbohydrate antigens. In breast cancer, these antigens are usually associated with a poor prognosis and a reduced overall survival. Cellular models have shown the implication of these antigens in cell adhesion, migration, proliferation and tumour growth. The present review summarizes our current knowledge of glycosylation changes (structures, biosynthesis and occurrence) in breast cancer cell lines and primary tumours, and the consequences on disease progression and aggressiveness. The therapeutic strategies attempted to target tumour-associated carbohydrate antigens in breast cancer are also discussed

    Multidimensional individualised Physical ACTivity (Mi-PACT) - a technology-enabled intervention to promote physical activity in primary care: Study protocol for a randomised controlled trial

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    © 2015 Peacock et al. Background: Low physical activity is a major public health problem. New cost-effective approaches that stimulate meaningful long-term changes in physical activity are required, especially within primary care settings. It is becoming clear that there are various dimensions to physical activity with independent health benefits. Advances in technology mean that it is now possible to generate multidimensional physical activity 'profiles' that provide a more complete representation of physical activity and offer a variety of options that can be tailored to the individual. Mi-PACT is a randomised controlled trial designed to examine whether personalised multidimensional physical activity feedback and self-monitoring alongside trainer-supportive sessions increases physical activity and improves health outcomes in at-risk men and women. Methods/Design: We aim to recruit 216 patients from within primary care aged 40 to 70years and at medium or high risk of cardiovascular disease and/or type II diabetes mellitus. Adopting an unequal allocation ratio (intervention: control) of 2:1, participants will be randomised to one of two groups, usual care or the intervention. The control group will receive usual care from their general practitioner (GP) and standardised messages about physical activity for health. The intervention group will receive physical activity monitors and access to a web-based platform for a 3-month period to enable self-monitoring and the provision of personalised feedback regarding the multidimensional nature of physical activity. In addition, this technology-enabled feedback will be discussed with participants on 5 occasions during supportive one-to-one coaching sessions across the 3-month intervention. The primary outcome measure is physical activity, which will be directly assessed using activity monitors for a 7-day period at baseline, post intervention and at 12months. Secondary measures (at these time-points) include weight loss, fat mass, and markers of metabolic control, motivation and well-being. Discussion: Results from this study will provide insight into the effects of integrated physical activity profiling and self-monitoring combined with in-person support on physical activity and health outcomes in patients at risk of future chronic disease. Trial registration:ISRCTN18008011Trial registration date: 31 July 201

    Chiropractic and self-care for back-related leg pain: design of a randomized clinical trial

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    <p>Abstract</p> <p>Background</p> <p>Back-related leg pain (BRLP) is a common variation of low back pain (LBP), with lifetime prevalence estimates as high as 40%. Often disabling, BRLP accounts for greater work loss, recurrences, and higher costs than uncomplicated LBP and more often leads to surgery with a lifetime incidence of 10% for those with severe BRLP, compared to 1-2% for those with LBP.</p> <p>In the US, half of those with back-related conditions seek CAM treatments, the most common of which is chiropractic care. While there is preliminary evidence suggesting chiropractic spinal manipulative therapy is beneficial for patients with BRLP, there is insufficient evidence currently available to assess the effectiveness of this care.</p> <p>Methods/Design</p> <p>This study is a two-site, prospective, parallel group, observer-blinded randomized clinical trial (RCT). A total of 192 study patients will be recruited from the Twin Cities, MN (n = 122) and Quad Cities area in Iowa and Illinois (n = 70) to the research clinics at WHCCS and PCCR, respectively.</p> <p>It compares two interventions: chiropractic spinal manipulative therapy (SMT) plus home exercise program (HEP) to HEP alone (minimal intervention comparison) for patients with subacute or chronic back-related leg pain.</p> <p>Discussion</p> <p>Back-related leg pain (BRLP) is a costly and often disabling variation of the ubiquitous back pain conditions. As health care costs continue to climb, the search for effective treatments with few side-effects is critical. While SMT is the most commonly sought CAM treatment for LBP sufferers, there is only a small, albeit promising, body of research to support its use for patients with BRLP.</p> <p>This study seeks to fill a critical gap in the LBP literature by performing the first full scale RCT assessing chiropractic SMT for patients with sub-acute or chronic BRLP using important <b>patient-oriented </b>and <b>objective biomechanical </b>outcome measures.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00494065">NCT00494065</a></p
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