Search PubMed⌕ Search

Biomedical subjects

Mauro Ferrari

Publications and source records attributed to Mauro Ferrari.

At least 37 records · Page 2Linked to original sources
PubMed2005

The molecular analysis of breast cancer utilizing targeted nanoparticle based ultrasound contrast agents.

This study was structured to challenge the hypothesis that nano-sized particulates could be molecularly targeted and bound to the prognostic and predictive HER-2/neu cell membrane receptor to elicit detectable changes in ultrasound response from human breast cancer cells. SKBR-3 human breast cancer cells were enlisted to test the efficacy of the particle conjugation strategy used in this study and ultimately, to provide conclusive remarks regarding the validity of the stated hypothesis. A characterization-mode ultrasound (CMUS) system was used to apply a continuum mechanics based, two-step inversion algorithm to reconstruct the mechanical material properties of four cell/agarose test conditions upon three independent test samples. The four test conditions include: Herceptin conjugated iron oxide nanoparticles bound to cells (HER-con), Herceptin bound to cells (HER), iso-type matched antibody conjugated iron oxide nanoparticles bound to cells (ISO-con), and Cold Flow Buffer mixed with agarose (CFB). The statistical analysis of these ultrasound results supported the ability to differentiate between HER-2/neu positive SKBR-3 cells that have been successfully tagged with Herceptin(R) conjugated iron oxide particles to those that have not demonstrated particle binding. These findings serve as promising proof-of-concept data for the development of a quantitative histopathologic evaluation tool directed towards both in situ and in vivo applications. The ultimate goal of this research is to exploit the molecular expression of the HER-2/neu protein to offer rapid, quantitative ultrasound information concerning the malignancy rating of human breast tissue employing tumor targeting nanoparticle based ultrasound contrast agents. When fully developed, this could potentially help 32,000-63,000 women efficiently find their proper treatment strategy to fight and win their battle against breast cancer.

Algorithms↗
PubMed2005

Endovascular repair of an aorto-left renal vein fistula due to a ruptured abdominal aortic aneurysm after EVAR.

PURPOSE: To report an unusual late complication of endovascular aneurysm repair: an arteriovenous fistula between the aneurysm sac and a retro-aortic left renal vein following sac expansion due to a type III endoleak. CASE REPORT: A 79-year-old man developed an arteriovenous fistula between the aneurysm sac and a retro-aortic left renal vein 67 months after endovascular aneurysm exclusion (EVAR). Aneurysm rupture was due to disconnection between the right iliac limb and an extender cuff. The problem was repaired percutaneously with another endograft bridging the two prostheses. At 16 months, the aneurysm sac diameter was decreased; there was no evidence of the AV fistula, and the patient was free from any complication related to the EVAR. CONCLUSIONS: This case emphasizes the need of close surveillance even in the late postoperative course of these patients. Moreover, this rare event confirmed that endovascular techniques can play an important role in treating emergent complications.

Aged↗
PubMed2005

Medical nanotechnology: shortening clinical trials and regulatory pathways?

Nanotechnology, the science of creating structures, devices, and systems with a length scale of approximately 1-100 nanometers, is poised to have a revolutionary effect on biomedical research and clinical science. By operating at the same scale as most biomacromolecules, nanoscale devices can afford a detailed view of the molecules and events that drive cellular systems and that lie at the heart of disease, and thus, nanotechnology can impact the drug discovery, development, and clinical testing of novel pharmaceuticals. Already, nanoscale drug delivery vehicles are in clinical use, but those successes represent just one way in which nanotechnology will prove useful. One promising nanoscale technology under development may provide real-time, in vivo measurements of apoptosis, and thus may afford an early signal of therapeutic efficacy, both in human clinical trials and in preclinical screening. Microfluidic systems, built of nanoscale components, can enable a host of rapid, massively parallel, high-throughput screening systems, while nanoscale sensors in a wide variety of formats are ready to provide multiplexed biochemical and genetic measurements in living systems. These advances could be utilized to shave time and expense from multiple stages of the drug discovery and development effort.

Biomedical Research↗
PubMed2004

Allelic genes involved in artery compliance and susceptibility to sporadic abdominal aortic aneurysm.

Vascular smooth muscle cells (VSMCs) synthesize elastin (ELN), major protein of aortic tunica media which confers strength and elasticity to aortic wall. Protein loss or distortion is typical in aneurysm tunica media. Transforming growth factor beta1 (TGFbeta1) inhibits growth and connective protein expression of abdominal VSMCs cultures. Also, in atherogenic studies, estrogen (but not estrogen plus progestin) treatments inhibit aortic collagen accumulation and elastic loss, risk factors to subsequent aortic enlargement. Therefore, polymorphisms of ELN, estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor (PR) and TGFbeta1 genes and their products may be involved in the abdominal aortic aneurysm (AAA) development. Using PCR-RFLP method, we analyzed ELN RmaI (exon 16), ERalphaPvuII-XbaI (intron 1), ERbetaAluI (exon 8), PR TaqI (intron 7) and TGFbeta1 Bsu36I (-509 bp, promoter) polymorphisms in 324 Caucasian male subjects: 225 healthy controls (mean age 71.20 +/- 6.85 years) and 99 unrelated AAA patients (mean age 69.8 +/- 7.1 years). No difference in ELN, ERalpha, PR and TGFbeta1 allele frequencies was observed in AAA patients versus controls (P > 0.05). However, because possessing at least an ERbetaAluI restriction site was statistically associated to AAA onset (chi(2) = 5.220; OR = 1.82, P < 0.05), ERbeta polymorphism was proposed as genetic determinant in the AAA susceptibility.

Aged↗
PubMed2004

Micropatterning of endothelial cells by guided stimulation with angiogenic factors.

Micropatterning technology holds significant promise in the development of micro/nanomedical devices. The precise control of cell position and migration is important in several applications. For example, the optimal design of implantable devices depends on the implant material's micro-and nano-texture, which influences the response of nearby tissue, including the microvessels. Therefore, we were interested in endothelial cell positioning and colonization on specific surface domains in the size range of microvasculature. To this end, endothelial cells were seeded in microfabricated grooves and exposed to vascular endothelial growth factor (VEGF), which plays a key role in the angiogenic response. Patterned silicon wafers with grooves of 50 microm width and depth and 150 microm groove spacing were used. Each patterned region had two semicircular ports at either end, one of which was used to seed human retinal endothelial cells (HREC) and the other to house VEGF embedded in Matrigel. After 1 week, cells were fixed and analyzed by laser scanning cytometry (LSC). Our results shows that we can control HREC seeding and positioning in surface grooves and that the speed of colonization of the grooves can be manipulated by local VEGF application. We were able to quantify this effect, showing that HREC relocate inside the grooves twice as fast in response to VEGF stimulation, compared to control conditions, at a speed of 3.14 +/- 0.01 and 1.55 +/- 0.01 microm/min, respectively. Our approach could be used towards the fabrication of "designer" substrates or devices that not only allow patterned cell growth, but also permit dynamic cell repositioning.

Angiogenesis Inducing Agents↗
PubMed2004

Adhesion of microfabricated particles on vascular endothelium: a parametric analysis.

"Smart" drug delivery systems should be selective and effective to ensure drug administration at the right time, at the right dosage, and anywhere in the body. Among the several administration routes and delivery systems that have been proposed, one of the most effective and promising is based on microfabricated particles injected directly into the blood stream. The shape, size, and material properties of the particles can be designed and optimized depending on the specific applications and targets (cell, tissue, or circulating virus). Since the binding affinity of particles to cells is affected by both the binding force and its growth rate with time, it is of great importance to consider the viscous response of the system. In this work, a parametric analysis is presented where the probability of adhesion of a microfabricated particle on the endothelium is expressed as a function of (i) the hemodynamic conditions, (ii) the viscoelastic properties of the particle and targeted cell, and (iii) density of ligands grafted over the particle. Criteria for the optimal design of particles are proposed.

Adsorption↗
PubMed2004

Opportunities for nanotechnology-based innovation in tissue proteomics.

Within this review we discuss two methodologies used in tissue proteomics, namely mass-spectrometry (MS)-based protein pattern diagnostics and protein microarrays. Further, we describe current goals within the field of tissue proteomics and suggest points of departure for designing nanotechnology-based tools that will enhance the role of molecularly based diagnostics and therapeutics development in clinical medicine.

Animals↗
PubMed2004

Abdominal aortic aneurysm: contrast-enhanced US for missed endoleaks after endoluminal repair.

PURPOSE: To evaluate contrast material-enhanced ultrasonography (US) for depiction of endoleaks after endovascular abdominal aortic aneurysm repair (or endovascular aneurysm repair [EVAR]) in patients with aneurysm enlargement and no evidence of endoleak. MATERIALS AND METHODS: From November 1998 to February 2003, 112 patients underwent EVAR. At follow-up, duplex US and biphasic multi-detector row computed tomographic (CT) angiography were performed. In 10 patients (group A), evident aneurysm enlargement was observed, with no evidence of complications, at both CT angiography and duplex US. Group A patients, 10 men (mean age, 69.6 years +/- 10 [standard deviation]), underwent US after intravenous bolus injection of a second-generation contrast agent, with continuous low-mechanical index (0.01-0.04) real-time tissue harmonic imaging. Group B patients, 10 men (mean age, 71.3 years +/- 8.2) with aneurysm shrinkage and no evidence of complications, and group C patients, 10 men (mean age, 73.2 years +/- 6) with CT angiographic evidence of endoleak, underwent contrast-enhanced US. Digital subtraction angiography (DSA) was performed in groups A and C. Endoleak detection and characterization were assessed with imaging modalities used in groups A-C; at contrast-enhanced US, time of detection of endoleak, persistence of sac enhancement, and morphology of enhancement were evaluated. RESULTS: In group A, contrast-enhanced US depicted one type I, six type II, one type III, and two undefined endoleaks that were not detected at CT angiography. All leakages were characterized by slow and delayed echo enhancement detected at longer than 150 seconds after contrast agent administration. DSA results confirmed findings in all patients; percutaneous treatment was performed. In group B, contrast-enhanced US did not show echo enhancement; in group C, results with this modality confirmed findings at CT angiography and DSA. CONCLUSION: Contrast-enhanced US depicts endoleaks after EVAR, particularly when depiction fails with other imaging modalities.

Aged↗
PubMed2004

Nanotechnology and tumor imaging: seizing an opportunity.

Nanoparticles, labeled with a signaling moiety for in vivo imaging, and one or more ligands for molecularly targeted specificity, hold considerable promise in oncology. Nanoparticles can serve as modular platforms, from which a wide variety of highly sensitive and specific imaging agents can be created. For example, many hundreds or thousands of atoms that provide imaging signals, such as radioisotopes, lanthanides, or fluorophores, can be attached to each nanoparticle, to form imaging agents that would provide higher sensitivity that can be obtained from agents based on small molecules. Similarly, many copies of targeted ligands can be attached to nanoparticles to markedly increase specific binding. Drugs or therapeutic isotopes can be added to create multifunctional nanoparticles. Appropriately labeled and targeted nanoparticles could lead to a paradigm change in which cancer detection, diagnosis, and therapy are combined in a single molecular complex.

Humans↗
PubMed2004

Object-oriented design tools for supramolecular devices and biomedical nanotechnology.

Nanotechnology provides multifunctional agents for in vivo use that increasingly blur the distinction between pharmaceuticals and medical devices. Realization of such therapeutic nanodevices requires multidisciplinary effort that is difficult for individual device developers to sustain, and identification of appropriate collaborations outside ones own field can itself be challenging. Further, as in vivo nanodevices become increasingly complex, their design will increasingly demand systems level thinking. System engineering tools such as object-oriented analysis, object-oriented design (OOA/D) and unified modeling language (UML) are applicable to nanodevices built from biological components, help logically manage the knowledge needed to design them, and help identify useful collaborative relationships for device designers. We demonstrate the utility of these systems engineering tools by reverse engineering an existing molecular device (the bacmid molecular cloning system) using them, and illustrate how object-oriented approaches identify fungible components (objects) in nanodevices in a way that facilitates design of families of related devices, rather than single inventions. We also explore the utility of object-oriented approaches for design of another class of therapeutic nanodevices, vaccines. While they are useful for design of current nanodevices, the power of systems design tools for biomedical nanotechnology will become increasingly apparent as the complexity and sophistication of in vivo nanosystems increases. The nested, hierarchical nature of object-oriented approaches allows treatment of devices as objects in higher-order structures, and so will facilitate concatenation of multiple devices into higher-order, higher-function nanosystems.

Baculoviridae↗
PubMed2003

Recommendations of the National Heart, Lung, and Blood Institute Nanotechnology Working Group.

Recent rapid advances in nanotechnology and nanoscience offer a wealth of new opportunities for diagnosis and therapy of cardiovascular, pulmonary, and hematologic diseases and sleep disorders. To review the challenges and opportunities offered by these nascent fields, the National Heart, Lung, and Blood Institute convened a Working Group on Nanotechnology. Working Group participants discussed the various aspects of nanotechnology and its applications to heart, lung, blood, and sleep (HLBS) diseases. This report summarizes their discussions according to scientific opportunities, perceived needs and barriers, specific disease examples, and recommendations on facilitating research in the field. An overarching recommendation of the Working Group was to focus on translational applications of nanotechnology to solve clinical problems. The Working Group recommended the creation of multidisciplinary research centers capable of developing applications of nanotechnology and nanoscience to HLBS research and medicine. Centers would also disseminate technology, materials, and resources and train new investigators. Individual investigators outside these centers should be encouraged to conduct research on the application of nanotechnology to biological and clinical problems. Pilot programs and developmental research are needed to attract new investigators and to stimulate creative, high-impact research. Finally, encouragement of small businesses to develop nanotechnology-based approaches to clinical problems was considered important.

Animals↗
PubMed2003

T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions.

Atherosclerotic lesions are infiltrated by macrophages and T lymphocytes, potentially reactive to pathogens. We studied in vivo activated T lymphocytes that infiltrate atherosclerotic plaques of Helicobacter pylori-infected patients with or without anti-Chlamydia pneumoniae antibodies. In all atherosclerotic lesions, T helper type 1 (Th1) cells were predominant. C. pneumoniae-specific T cells were detected only in the plaques of anti-C. pneumoniae seropositive patients, whereas H. pylori-specific T cells were found in the gastric mucosa but not in the plaques of the same patients. Plaque-derived Th1 cells expressed cytotoxicity, proapoptotic activity, and help for monocyte tissue factor production. Although multifactorial, atherosclerosis can be regarded as a Th1-driven immunopathological condition.

Antibodies, Bacterial↗
PubMed2003

Evaluation of the proximal aortic neck enlargement following endovascular repair of abdominal aortic aneurysm: 3-years experience.

The aim of this study was to evaluate incidence, potential risk factors and effects on stent-graft migration of proximal neck dilatation after endoluminal repair of abdominal aortic aneurysm (EVAR), and the role of ultrasound (US) in detecting neck enlargement. From November 1998 to October 2001, 90 patients underwent EVAR. On follow-up, US and CT angiography (CTA) were performed, and diameters of the suprarenal and infrarenal aortic necks were monitored. Incidence of significant neck enlargement (> or =2.5 mm) and distal stent-graft migration (>10 mm) was calculated. Several factors were evaluated as predictive of neck enlargement. Ultrasound and CTA measurements were compared. The US and CTA examinations were available in 68, 39, and 11 patients at 1, 2, and 3 years follow-up (mean follow-up 15 months). Incidence of significant neck dilatation was 21.8% at the infrarenal level (13, 33, and 36% at 1, 2, and 3 years follow-up) and 13.8% at the suprarenal level (9, 18, and 27% at 1, 2, and 3 years follow-up). Significant stent-graft migration occurred in 14 of 87 patients (16%) and was associated with neck dilatation in 8 (2 suprarenal and 6 infrarenal). No risk factors were identified. Ultrasound was less accurate than CT in measuring neck diameter, in particular at the suprarenal level. Proximal aortic neck enlargement occurs in up to 30% of patients after EVAR and represents the main risk factor for stent-graft migration. The risk of infrarenal neck dilatation is higher at 2 years follow-up, whereas the suprarenal neck enlarges later. Ultrasound is not useful in monitoring neck diameter.

Aged↗
PubMed2003

Interstitial stress and fluid pressure within a growing tumor.

A solid tumor is composed of a population of cells that is expanding as a result of cell division. With dense cell packing, the solid matrix of the interstitial tissue is subject to residual stress. In addition, elevated interstitial fluid pressure (IFP) has been reported by researchers for a number of solid tumors. These features were incorporated into a mathematical model that predicts the mechanical response of a solid tumor within its host environment. A theoretical framework accounting for volumetric expansion, transvascular exchange and extravascular transport of fluids was developed using poroelastic theory, and applied to a spherical, vascularized, alymphatic tumor undergoing small growth increments. Simulations of tumor IFP were similar to those predicted by Jain and Baxter, showing elevated IFP that is driven by microvascular fluid pressure. Tumor growth, tissue stiffness, and IFP contribute to the compressive stresses predicted in the solid tumor interior. Tensile and compressive stresses were predicted in adjacent host tissues corresponding to radial and circumferential directions, respectively. An application of this model includes a solid stress-based framework for predicting regions of vascular collapse within the tumor interior.

Blood Pressure↗
PubMed2002

Mechanical spectral signatures of malignant disease? A small-sample, comparative study of continuum vs. nano-biomechanical data analyses.

Thin sections from human breast biopsies were employed to perform a differential analysis of the ultrasound spectral responses from invasive ductal carcinoma and normal tissue. A non-destructive testing methodology was employed, yielding the reflection coefficients as function of frequency in the clinical ultrasound range. The spectral responses were simulated both in the context of continuum and nano-biomechanics, with the objective of quantifying the physical properties that determine the differences in the spectral signature of normal vs. malignant tissue. The properties that were employed for the theoretical reconstruction of the spectra were: the density, the continuum and the nanomechanical elastic constants, and the nanomechanical theory internodal distance. The latter is a measure of the depth-of-penetration of mechanical actions between contiguous tissue elements. Together with vectorial descriptors of the tissue spatial arrangement, the internodal distance variable affords the quantitative incorporation of tissue architectural data in the theoretical model. In this paper, the validity of the nanomechanical approach to tissue characterization is discussed, and its potential extensions to biomolecular marker-based cancer diagnostics and therapeutics are considered.

Breast Neoplasms↗
PubMed2002

Noninvasive diagnosis of incomplete endovascular aneurysm repair: D-dimer assay to detect type I endoleaks and nonshrinking aneurysms.

PURPOSE: To test the hypothesis that D-dimer (D-D), a cross-linked fibrin degradation product of an ongoing thrombotic event, could be a marker for incomplete aneurysm exclusion after endovascular abdominal aortic aneurysm (AAA) repair. METHODS: In a multicenter study, 83 venous blood samples were collected from 74 AAA endograft patients and controls. Twenty subjects who were >6 months postimplantation and had evidence of an endoleak and/or an unmodified or increasing AAA sac diameter formed the test group. Controls were 10 nondiseased subjects >65 years old, 18 AAA surgical candidates, and 26 postoperative endograft patients with no endoleak and a shrinking aneurysm. Blood samples were analyzed for D-D through a latex turbidimetric immunoassay. The endograft patients were stratified into 5 clinical groups for analysis: no endoleak and decreasing sac diameter, no endoleak and increasing/unchanged sac diameter, type II endoleak and decreasing sac diameter, type II endoleak and increasing/unchanged sac diameter, and type I endoleak. RESULTS: Individual D-D values were highly variable, but differences among clinical groups were statistically significant (p < 0.0001). D-D values did not vary significantly between patients with stable, untreated AAAs and age-matched controls (238 +/- 180 ng/mL versus 421 +/- 400 ng/mL, p > 0.05). Median D-D values increased at 4 days postoperatively (963 ng/mL versus 382 ng/mL, p > 0.05) and did not vary thereafter if there was no endoleak and the aneurysm sac decreased. D-D mean values were higher in patients with type I endoleak (1931 +/- 924 ng/mL, p < 0.005) and those with unchanged/increasing sac diameters (1272 +/- 728 ng/mL) than in cases with decreasing diameters (median 638 +/- 238 ng/mL) despite the presence of endoleak (p < 0.0005). CONCLUSIONS: Elevated D-D may prove to be a useful marker for fixation problems after endovascular AAA repair and may help rule out type I endoleak, thus excluding patients from unnecessary invasive tests.

Angiography↗