292 research outputs found

    Targeted microbubbles: a novel application for the treatment of kidney stones

    Get PDF
    Kidney stone disease is endemic. Extracorporeal shockwave lithotripsy was the first major technological breakthrough where focused shockwaves were used to fragment stones in the kidney or ureter. The shockwaves induced the formation of cavitation bubbles, whose collapse released energy at the stone, and the energy fragmented the kidney stones into pieces small enough to be passed spontaneously. Can the concept of microbubbles be used without the bulky machine? The logical progression was to manufacture these powerful microbubbles ex vivo and inject these bubbles directly into the collecting system. An external source can be used to induce cavitation once the microbubbles are at their target; the key is targeting these microbubbles to specifically bind to kidney stones. Two important observations have been established: (i) bisphosphonates attach to hydroxyapatite crystals with high affinity; and (ii) there is substantial hydroxyapatite in most kidney stones. The microbubbles can be equipped with bisphosphonate tags to specifically target kidney stones. These bubbles will preferentially bind to the stone and not surrounding tissue, reducing collateral damage. Ultrasound or another suitable form of energy is then applied causing the microbubbles to induce cavitation and fragment the stones. This can be used as an adjunct to ureteroscopy or percutaneous lithotripsy to aid in fragmentation. Randall's plaques, which also contain hydroxyapatite crystals, can also be targeted to pre-emptively destroy these stone precursors. Additionally, targeted microbubbles can aid in kidney stone diagnostics by virtue of being used as an adjunct to traditional imaging methods, especially useful in high-risk patient populations. This novel application of targeted microbubble technology not only represents the next frontier in minimally invasive stone surgery, but a platform technology for other areas of medicine

    Experimental observations and numerical modeling of lipid-shell microbubbles with calcium-adhering moieties for minimally-invasive treatment of urinary stones

    Get PDF
    A novel treatment modality incorporating calcium-adhering microbubbles has recently entered human clinical trials as a new minimally-invasive approach to treat urinary stones. In this treatment method, lipid-shell gas-core microbubbles can be introduced into the urinary tract through a catheter. Lipid moities with calcium-adherance properties incorporated into the lipid shell facilitate binding to stones. The microbubbles can be excited by an extracorporeal source of quasi-collimated ultrasound. Alternatively, the microbubbles can be excited by an intraluminal source, such as a fiber-optic laser. With either excitation technique, calcium-adhering microbubbles can significantly increase rates of erosion, pitting, and fragmentation of stones. We report here on new experiments using high-speed photography to characterize microbubble expansion and collapse. The bubble geometry observed in the experiments was used as one of the initial shapes for the numerical modeling. The modeling showed that the bubble dynamics strongly depends on bubble shape and stand-off distance. For the experimentally observed shape of microbubbles, the numerical modeling showed that the collapse of the microbubbles was associated with pressure increases of some two-to-three orders of magnitude compared to the excitation source pressures. This in-vitro study provides key insights into the use of microbubbles with calcium-adhering moieties in treatment of urinary stones

    Association between Randall's Plaque and Calcifying Nanoparticles

    Get PDF
    Randall's plaques, first described by Alexander Randall in the 1930s, are small subepithelial calcifications in the renal papillae (RP) that also extend deeply into the renal medulla. Despite the strong correlation between the presence of these plaques and the formation of renal stones, the precise origin and pathogenesis of Randall s plaque formation remain elusive. The discovery of calcifying nanoparticles (CNP) and their detection in many calcifying processes of human tissues has raised hypotheses about their possible involvement in renal stone formation. We collected RP and blood samples from 17 human patients who had undergone laparoscopic nephrectomy due to neoplasia. Homogenized RP tissues and serum samples were cultured for CNP. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis were performed on fixed RP samples. Immunohistochemical staining (IHS) was applied on the tissue samples using CNP-specific monoclonal antibody (mAb). Randall s plaques were visible on gross inspection in 11 out of 17 collected samples. Cultures of all serum samples and 13 tissue homogenates had CNP growth within 4 weeks. SEM revealed spherical apatite formations in 14 samples, with calcium and phosphate peaks detected by EDS analysis. IHS was positive in 9 out of 17 samples. A strong link was found between the presence of Randall s plaques and the detection of CNP, also referred to as nanobacteria. These results suggest new insights into the etiology of Randall's plaque formation, and will help us understand the pathogenesis of stone formation. Further studies on this topic may lead us to new approaches on early diagnosis and novel medical therapies of kidney stone formation

    Gender and Management: new directions in research and continuing patterns in practice

    Get PDF
    This is the author’s version of the following article. The definitive version is available at www.interscience.wiley.com:Adelina Broadbridge and Jeff Hearn, Gender and management: New directions in research and continuing patterns in practice, 2008, British Journal of Management, (19), s1, 38-49. http://dx.doi.org/10.1111/j.1467-8551.2008.00570.xCopyright: British Academy of Management, Blackwell Publishing Ltdhttp://www.blackwellpublishing.com

    Effect of Tamsulosin on Stone Passage for Ureteral Stones: A Systematic Review and Meta-analysis

    Full text link
    Study objectiveTamsulosin is recommended for patients receiving a diagnosis of a ureteral stone less than 10 mm who do not require immediate urologic intervention. Because of conflicting results from recent meta-analyses and large randomized controlled trials, the efficacy of tamsulosin is unclear. We perform a systematic review and meta-analysis to investigate the effect of tamsulosin on stone passage in patients receiving a diagnosis of ureteral stone.MethodsMEDLINE, EMBASE, and CENTRAL databases were searched without language restriction through November 2015 for studies assessing the efficacy of tamsulosin and using a double-blind, randomized, controlled trial design. Meta-analysis was conducted with a random-effects model and subgroup analyses were conducted to determine sources of heterogeneity.ResultsEight randomized controlled trials (N=1,384) contained sufficient information for inclusion. The pooled risk of stone passage in the tamsulosin arm was 85% versus 66% in the placebo arm, but substantial heterogeneity existed across trials (I2=80.2%; P<.001). After stratifying of studies by stone size, the meta-analysis of the large stone subgroup (5 to 10 mm; N=514) indicated a benefit of tamsulosin (risk difference=22%; 95% confidence interval 12% to 33%; number needed to treat=5). The meta-analysis of the small stone subgroup (<4 to 5 mm; N=533) indicated no benefit (risk difference=-0.3%; 95% confidence interval -4% to 3%). Neither meta-analysis for the occurrence of dizziness or hypotension showed a significant effect.ConclusionTamsulosin significantly improves stone passage in patients with larger stones, whereas the effect of tamsulosin is diminished in those with smaller stones, who are likely to pass their stone regardless of treatment

    Introduction to “Binary Binds”: Deconstructing Sex and Gender Dichotomies in Archaeological Practice

    Get PDF
    YesGender archaeology has made significant strides toward deconstructing the hegemony of binary categorizations. Challenging dichotomies such as man/woman, sex/gender, and biology/culture, approaches informed by poststructuralist, feminist, and queer theories have moved beyond essentialist and universalist identity constructs to more nuanced configurations. Despite the theoretical emphasis on context, multiplicity, and fluidity, binary starting points continue to streamline the spectrum of variability that is recognized, often reproducing normative assumptions in the evidence. The contributors to this special issue confront how sex, gender, and sexuality categories condition analytical visibility, aiming to develop approaches that respond to the complexity of theory in archaeological practice. The papers push the ontological and epistemological boundaries of bodies, personhood, and archaeological possibility, challenging a priori assumptions that contain how sex, gender, and sexuality categories are constituted and related to each other. Foregrounding intersectional approaches that engage with ambiguity, variability, and difference, this special issue seeks to “de-contain” categories, assumptions, and practices from “binding” our analytical gaze toward only certain kinds of persons and knowledges, in interpretations of the past and practices in the present
    • …
    corecore