Cystatin C--a paradigm of evidence based laboratory medicine

Cystatin C is a 13-kDa protein, of the cysteine proteinase inhibitor superfamily, produced by all nucleated cells. Its production rate is constant throughout the ages of 1 to 50 years. It is freely filtered at the glomerulus and then resorbed and fully catabolised by proximal renal tubules, making it an ideal marker of glomerular filtration rate (GFR). Serum creatinine, the most established marker of renal function, is affected by age, gender, muscle mass, nutritional status and analytical interference. The abbreviated Modifiation of Diet in Renal Diseases (MDRD) equation has recently been introduced in an attempt to overcome these shortcomings, but still has many limitations. Cystatin C is not affected by gender, muscle mass, malignancy, its production rate is usually constant and its plasma concentration therefore is dependent only on GFR. Cystatin C has been demonstrated to be more accurate than serum creatinine in the detection of early renal impairment and in specific populations may allow for early detection of renal disease. Cystatin C has also been found to be a strong predictor of long-term clinical outcomes in patients with cardiovascular diseases. Although cystatin C may have advantages in detection of early renal impairment there is a paucity of evidence that it significantly improves clinical decision making over creatinine. This coupled with assay cost may be the reason why cystatin C, although well recognised, has not been introduced into routine operational use, although that may eventuate with emerging evidence.     

Fluoxetine: a review on evidence based medicine

BACKGROUND: Fluoxetine was the first molecule of a new generation of antidepressants, the Selective Serotonin Re-uptake Inhibitors (SSRIs). It is recurrently the paradigm for the development of any new therapy in the treatment of depression. Many controlled studies and meta-analyses were performed on Fluoxetine, to improve the understanding of its real impact in the psychiatric area. The main objective of this review is to assess the quality and the results reported in the meta-analyses published on Fluoxetine. METHODS: Published articles on Medline, Embase and Cochrane databases reporting meta-analyses were used as data sources for this review.Articles found in the searches were reviewed by 2 independent authors, to assess if these were original meta-analyses. Only data belonging to the most recent and comprehensive meta-analytic studies were included in this review. RESULTS: Data, based on a group of 9087 patients, who were included in 87 different randomized clinical trials, confirms that fluoxetine is safe and effective in the treatment of depression from the first week of therapy. Fluoxetine's main advantage over previously available antidepressants (TCAs) was its favorable safety profile, that reduced the incidence of early drop-outs and improved patient's compliance, associated with a comparable efficacy on depressive symptoms. In these patients, Fluoxetine has proven to be more effective than placebo from the first week of therapy.Fluoxetine has shown to be safe and effective in the elderly population, as well as during pregnancy. Furthermore, it was not associated with an increased risk of suicide in the overall evaluation of controlled clinical trials.The meta-analysis available on the use of Fluoxetine in the treatment of bulimia nervosa shows that the drug is as effective as other agents with fewer patients dropping out of treatment.Fluoxetine has demonstrated to be as effective as chlomipramine in the treatment of Obsessive-Compulsive-Disorder (OCD). CONCLUSION: Fluoxetine can be considered a drug successfully used in several diseases for its favorable safety/efficacy ratio. As the response rate of mentally ill patients is strictly related to each patient's personal characteristics, any new drug in this area, will have to be developed under these considerations.     

Regenerative medicine based applications to combat stress urinary incontinence

Stress urinary incontinence (SUI), as an isolated symptom, is not a life threatening condition. However, the fear of unexpected urine leakage contributes to a significant decline in quality of life parameters for afflicted patients. Compared to other forms of incontinence, SUI cannot be easily treated with pharmacotherapy since it is inherently an anatomic problem. Treatment options include the use of bio-injectable materials to enhance closing pressures, and the placement of slings to bolster fascial support to the urethra. However, histologic findings of degeneration in the incontinent urethral sphincter invite the use of tissues engineering strategies to regenerate structures that aid in promoting continence. In this review, we will assess the role of stem cells in restoring multiple anatomic and physiological aspects of the sphincter. In particular, mesenchymal stem cells and CD34⁺ cells have shown great promise to differentiate into muscular and vascular components, respectively. Evidence supporting the use of cytokines and growth factors such as hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and insulin-like growth factor further enhance the viability and direction of differentiation. Bridging the benefits of stem cells and growth factors involves the use of synthetic scaffolds like poly (1,8-octanediol-co-citrate) (POC) thin films. POC scaffolds are synthetic, elastomeric polymers that serve as substrates for cell growth, and upon degradation, release growth factors to the microenvironment in a controlled, predictable fashion. The combination of cellular, cytokine and scaffold elements aims to address the pathologic deficits to urinary incontinence, with a goal to improve patient symptoms and overall quality of life.     

Evidence based medicine: an approach to clinical problem-solving.

Doctors within the NHS are confronting major changes at work. While we endeavour to improve the quality of health care, junior doctors'' hours have been reduced and the emphasis on continuing medical education has increased. We are confronted by a growing body of information, much of it invalid or irrelevant to clinical practice. This article discusses evidence based medicine, a process of turning clinical problems into questions and then systematically locating, appraising, and using contemporaneous research findings as the basis for clinical decisions. The computerisation of bibliographies and the development of software that permits the rapid location of relevant evidence have made it easier for busy clinicians to make best use of the published literature. Critical appraisal can be used to determine the validity and applicability of the evidence, which is then used to inform clinical decisions. Evidence based medicine can be taught to, and practised by, clinicians at all levels of seniority and can be used to close the gulf between good clinical research and clinical practice. In addition it can help to promote self directed learning and teamwork and produce faster and better doctors.     

Gene mutation‐based and specific therapies in precision medicine

Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application. Therapeutic strategies of precision medicine should be considered according to gene mutation, after biological and functional mechanisms of mutated gene expression or epigenetics, or the correspondent protein, are clearly validated. It is time to explore and develop a strategy to target and correct mutated genes by direct elimination, restoration, correction or repair of mutated sequences/genes. Nevertheless, there are still numerous challenges to integrating widespread genomic testing into individual cancer therapies and into decision making for one or another treatment. There are wide‐ranging and complex issues to be solved before precision medicine becomes clinical reality. Thus, the precision medicine can be considered as an extension and part of clinical and translational medicine, a new alternative of clinical therapies and strategies, and have an important impact on disease cures and patient prognoses.     

Polymer‐based microparticles in tissue engineering and regenerative medicine

Different types of biomaterials, processed into different shapes, have been proposed as temporary support for cells in tissue engineering (TE) strategies. The manufacturing methods used in the production of particles in drug delivery strategies have been adapted for the development of microparticles in the fields of TE and regenerative medicine (RM). Microparticles have been applied as building blocks and matrices for the delivery of soluble factors, aiming for the construction of TE scaffolds, either by fusion giving rise to porous scaffolds or as injectable systems for in situ scaffold formation, avoiding complicated surgery procedures. More recently, organ printing strategies have been developed by the fusion of hydrogel particles with encapsulated cells, aiming the production of organs in in vitro conditions. Mesoscale self‐assembly of hydrogel microblocks and the use of leachable particles in three‐dimensional (3D) layer‐by‐layer (LbL) techniques have been suggested as well in recent works. Along with innovative applications, new perspectives are open for the use of these versatile structures, and different directions can still be followed to use all the potential that such systems can bring. This review focuses on polymeric microparticle processing techniques and overviews several examples and general concepts related to the use of these systems in TE and RE applications. The use of materials in the development of microparticles from research to clinical applications is also discussed. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011