Search PubMed⌕ Search

Biomedical subjects

R De Santis

Publications and source records attributed to R De Santis.

At least 19 recordsLinked to original sources

An experimental and theoretical composite model of the human mandible.

The purpose is to design and manufacture a composite mandible replicate suitable for testing the influence of prosthetic materials on the stress distribution of bone. Composite mandibles made of a poly(methylmethacrylate) core and a glass reinforced outer shell are manufactured and characterised through mechanical tests assisted by the finite element analysis. The mandible replicate has been conveniently equipped with strain gauges, moreover a video extensometer has also been used in order to measure the arch width change during loading. A close agreement is found between the experimental data and the theoretical predictions. By laterally loading the mandibles the maximum values of stress and strain take place in the premolar-incisal region. By varying technological parameters such as the fiber volume fraction and orientation, it is easy to replicate the behaviour of mandibles having different stiffnesses. The results obtained by laterally loading the composite mandibles through the condyles or through the gonion regions are consistent with literature data relative to the arch width decrease of natural jaws during opening and closing. This novel synthetic system coupled with the Finite Element model constitutes an experimental-theoretical model suitable to investigate the biomechanical effects of oral rehabilitations on mandibular bone.

Humans↗

Mandibular intrabony lesion as first sign of sarcoidosis: case report.

A 33-year-old woman with intra-bony sarcoidosis of the mandible is reported. This presentation of sarcoidosis was the first sign of the disease in this patient, and was treated surgically because of an inaccurate biopsy report. Medical therapy was instituted once the diagnosis was made, and the disease was well controlled (including the mandibular localization) at 2 years follow-up.

Adult↗

Presence of TT virus DNA in bone marrow cells from hematologic patients.

Recent observations suggest that TT virus (TTV), in addition to liver, may also infect bone marrow. In this study, bone marrow samples and sera from 33 patients with haematological disorders and sera from 16 healthy controls were investigated for TTV DNA presence. Altogether TTV DNA sequences were demonstrated in bone marrow cells of 84.84% of patients. Moreover TTV DNA was detected in sera from 72.72% of patients and from 93.75% of controls. N22 sequences amplified from bone marrow cells and serum of 3 patients were analysed, after cloning: all these isolates were of type 2c and 2 or 3 variants were present in each isolate. After single strand DNA degradation, replicative forms were detectable in BM cells. This finding, in addition to the detection of variants similar in the BM and in the serum of the same patient could suggest that BM is a site of TTV replication (or one of the sites) from which the virus is spread in blood.

Antibodies, Viral↗

Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches.

BACKGROUND: Although a growing body of literature regarding polyoma BK virus (BKV) infection and associated interstitial nephritis in kidney-allograft recipients is becoming available, the impact of BKV infection in the pediatric population has not been fully evaluated. METHODS: In a retrospective analysis, we performed polymerase chain reaction (PCR) assays for BKV DNA in serum and urine samples from 100 pediatric kidney-allograft recipients referred to our institution in the last 5 years. RESULTS: BKV viruria was observed in 26 of 100 patients, whereas BKV viremia was demonstrated in 5 patients. Serum creatinine was significantly higher in recipients with positive BK viremia compared with BKV DNA-negative patients (mean 2.66 vs. 1.14 mg/100 mL). Renal biopsy performed in 3 of 5 patients showed graft damage consistent with interstitial nephropathy. In the univariate analysis, negative antibody status of the recipient and the presence of mycophenolate mofetil in baseline immunosuppression were the two factors predictive of active BKV infection. CONCLUSIONS: Our study shows that BKV-associated nephropathy is a relevant complication in the pediatric kidney transplantation setting also. Identification of patients at risk of developing virus-associated nephropathy, through prospective quantification of viral load, could improve clinical outcome by allowing the use of timely preemptive therapy guided by BKV DNA levels.

Adolescent↗

Novel antitenascin antibody with increased tumour localisation for Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT).

The Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT) method is based on intravenous, sequential administration of a biotinylated antibody, avidin/streptavidin and (90)Y-labelled biotin. The hybridoma clone producing the monoclonal antitenascin antibody BC4, previously used for clinical applications, was found not suitable for further development because of the production of an additional, nonfunctional light chain. In order to solve this problem, the new cST2146 hybridoma clone was generated. The monoclonal antibody ST2146, produced by this hybridoma, having the same specificity as BC4 but lacking the nonfunctional light chain, was characterised. ST2146 was found able to bind human tenascin at an epitope strictly related, if not identical, to the antigenic epitope of BC4. It showed, compared to BC4, higher affinity and immunoreactivity and similar selectivity by immunohistochemistry. Biodistribution studies of biotinylated ST2146 and three other monoclonal antitenascin antibodies showed for ST2146 the highest and more specific tumour localisation in HT29-grafted nude mice. On the overall, ST2146 appears to be a good alternative to BC4 for further clinical development of PAGRIT.

Animals↗

Dynamic mechanical behavior of PMMA based bone cements in wet environment.

The mechanical properties of three wet commercial bone cements, namely Braxel (from Bioland), Simplex-P (from Howmedica) and CMW1-G (from DePuy) are investigated by means of stress relaxation and dynamic mechanical analysis (DMA). The geometry of loading that was used is the three point bending method (ASTM D790); all the tests were performed in a water chamber by means of temperature sweeps between 17 and 57 degrees C and spanning four frequency decades. The results show that viscoelastic properties are strongly dependent on specimen conditioning (i.e. water uptake and heat treatment). The results also show that all the cements that were analyzed show mechanical properties which are intermediate between the ones of the cancellous bone and of the metals of which prostheses are normally made. As a consequence, the cement is able to reduce the stress concentrations due to the interfacing of materials which have very different stiffnesses. Moreover, the results of the DMA, particularly the ones concerning the damping factor (tan delta), indicate that at body temperature the bone cements tested show an increased capacity of dissipation, the higher is the loading frequency, thus displaying shock absorbing properties.

Journal Article↗

Spatial and structural dependence of mechanical properties of porcine intervertebral disc.

Structure-function relationship of natural tissues is crucial to design a device mimicking the structures present in human body. For this purpose, to provide guidelines to design an intervertebral disc (IVD) substitute, in this study the influence of the spatial location and structural components on the mechanical properties of porcine IVD was investigated. Local compressive stiffness (LCS) was measured on the overall disc, also constrained between the two adjacent vertebrae: the dependence on the lumbar position was evaluated. The compliance values in the anterior position (A) were higher than both in the central posterior (CP) and in the lateral-posterior (RP, LP) locations. The values of Young's Modulus (74.67+/-6.03 MPa) and compression break load (1.36x10(4)+/-0.09x10(4)N) of the disc were also evaluated by distributed compression test. The NP rheological behavior was typical of weak-gels, with elastic modulus G' always higher than viscous modulus G" all over the frequency range investigated (G' and G" respectively equal to 320 and 85 Pa at 1 Hz) and with the moduli trends were almost parallel to each other.

Journal Article↗

Coracoclavicular joint: osteologic study of 1020 human clavicles.

We examined 1020 dry clavicles from cadavers of Italian origin to determine the prevalence of the coracoclavicular joint (ccj), a diarthrotic synovial joint occasionally present between the conoid tubercle of the clavicle and the superior surface of the horizontal part of the coracoid process. Five hundred and nine clavicles from individuals of different ages were submitted to X-ray examination. Using radiography, we measured the entire length and the index of sinuosity of the anterior lateral curve, on which the distance between the conoid tubercle and the coracoid process depends. We also used radiography to record the differences in prevalence of arthritis in two neighbouring joints, the acromioclavicular and sternoclavicular joints. Of the 1020 clavicles, eight (0.8%) displayed the articular facet of the ccj. No statistical correlation was found between clavicular length and the index of sinuosity of the anterior lateral curve. The prevalence of arthritis in clavicles with ccj was higher than that revealed in clavicles without ccj. The prevalence of ccj in the studied clavicles is lower than that observed in Asian cohorts. Furthermore, ccj is not conditioned by either length or sinuosity of the anterior lateral curve of the clavicle. Finally, the assumption that ccj is a predisposing factor for degenerative changes of neighbouring joints is statistically justified.

Acromioclavicular Joint↗

Developmental genetics in primitive chordates.

Recent advances in the study of the genetics and genomics of urochordates testify to a renewed interest in this chordate subphylum, believed to be the most primitive extant chordate relatives of the vertebrates. In addition to their primitive nature, many features of their reproduction and early development make the urochordates ideal model chordates for developmental genetics. Many urochordates spawn large numbers of transparent and externally developing embryos on a daily basis. Additionally, the embryos have a defined and well-characterized cell lineage until the end of gastrulation. Furthermore, the genomes of the urochordates have been estimated to be only 5-10% of the size of the vertebrates and to have fewer genes and less genetic redundancy than vertebrates. Genetic screens, which are powerful tools for investigating developmental mechanisms, have recently become feasible due to new culturing techniques in ascidians. Because hermaphrodite ascidians are able to self-fertilize, recessive mutations can be detected in a single generation. Several recent studies have demonstrated the feasibility of applying modern genetic techniques to the study of ascidian biology.

Animals↗

TT virus contaminates first-generation recombinant factor VIII concentrates.

Recombinant factor VIII and factor IX concentrates, human-plasma-derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein-free) concentrates were negative for the virus. In 59% of patients treated with either first- or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin.

Blood Transfusion↗

Mechanical strength of tooth fragment reattachment.

The aim of this study was static and fatigue test investigation of the strength of a tooth fragment reattached with adhesives to the tooth body. Central bovine incisor teeth were used, and standardized fragments were obtained by cutting the incisal edge of the selected teeth. All the fragments were reattached using a multistep dentine adhesive system, and the specimens were randomly divided into two groups (A and B). Group B specimens underwent a further dental treatment: a circumferential double chamfer prepared around the external cut interface was filled with light cured composite restorative resin. Static and fatigue bending tests were performed and linear elastic equations were used to analyze and compare the strength of the treated teeth. The results indicated that the static and fatigue bending properties were improved by using reinforcement with composite restorative resin.

Acrylic Resins↗

Persistence of parvovirus B19 DNA in synovium of patients with haemophilic arthritis.

A progressive arthropathy develops commonly in haemophiliacs and its pathogenesis is not fully understood. Human parvovirus B19 has been associated with several diseases including acute and chronic arthropathy and some studies suggest its implication in chronic inflammatory diseases of the joints such as rheumatoid arthritis. In haemophiliacs parvovirus B19 infection occurs very frequently because of its transmission with plasma derivatives. In order to assess a role of B19 virus in haemophilic arthritis, synovial tissue samples from patients with haemophilia with arthritis and from patients, nonhaemophiliacs, with arthrosis or with joint trauma were examined for B19 DNA by nested PCR. In addition, the prevalence of antibody to parvovirus B19 NS1 protein as a possible serological marker of persistent B19 infection was tested and the association of the outcome of parvovirus infection with genetic diversity of B19 P6 promoter sequences was investigated. B19 DNA was detected in the synovial tissue of 31% of haemophiliacs with progressive arthropathy and of 5% of control patients. Fourteen out of 17 patients (82%) with haemophilic arthritis and with B19 DNA in their synovial membranes had IgG antibodies against the nonstructural protein NS1 of parvovirus B19. On the other hand, 19% of patients with haemophilia with B19 PCR negative synovial tissue and 21% of controls showed anti-NS1 antibodies. The P6 promoter presented specific sites of point mutations shared frequently by isolates from patients with haemophilia and arthritis. These results indicate that B19 DNA can persist in the synovial membranes of patients with haemophilic arthritis significantly more frequently in comparison to control individuals with arthrosis or joint trauma and show a correlation between anti- NS1 antibody presence and B19 DNA persistence in the synovial tissue.

Adolescent↗

Human herpesvirus 8 DNA sequences are present in bone marrow from HIV-negative patients with lymphoproliferative disorders and from healthy donors.

Bone marrow (BM) from patients affected by multiple myeloma (MM), exhibiting monoclonal gammopathy of undetermined significance (MGUS) or with non-Hodgkin lymphoma (NHL) as well as from healthy donors were investigated for the presence of human herpesvirus-8 (HHV-8) DNA sequences. ORF 26 sequences were detected in 36--56% of the patients and in 29% of the controls. In a few cases, two other HHV-8 DNA sequences were also detected. These observations indicate that the presence of the HHV-8 genome in BM is relatively common in different groups of patients as well as in healthy individuals and do not support an alleged role for HHV-8 in MM.

Bone Marrow↗

Polymer-based composite hip prostheses.

A composite hip prosthesis (CHP) made from poly(ether-imide) reinforced with carbon and glass fibres was manufactured and characterized. The main objective of the study was to evaluate the effect of fibre organization on the mechanical properties of the composite femoral implant and compare with the bone. A stacking sequence of drop-off plies of carbon/glass fibres reinforcing poly(ether-imide) (PEI) constitutes a symmetrical and balanced CHP. The hip was manufactured according to the finite element modelling (FEM) design and using the compression moulding and water-jet technologies. The measured stress-strain data according to tensile, flexural and torsional tests showed agreement with the numerical calculation. Young's modulus and the strength in tension are uniform along the stem axis (40 GPa and 600 MPa, respectively) while the elastic modulus in bending varies from 10 to 60 GPa in the tip-head direction. The composite stem showed a linear load-displacement relation up to 4500 N without breaking. Mechanical behaviour of the CHP is compared to that of a canine femur. Comparison with metal prostheses has also been undertaken. CHPs control stress-strain distributions, and hence the mechanical signals to bone, through a material-structure design.

Animals↗

Use of denaturing gradient gel electrophoresis for human polyomavirus JC sequence analysis.

Five genotypes of human polyomavirus JC (JCV) have been detected so far by nucleotide sequencing and by restriction fragment length polymorphism analysis. These genotypes are the result of geographically based virus evolution. However, interesting aspects of genotyping could involve both pathogenetic and diagnostic aspects. The product from amplification of JCV sequences, found in urine from 12 healthy individuals from different countries, have been analysed by denaturing gradient gel electrophoresis (DGGE) and by nucleotide sequencing. The aim of this study was to assess if the DGGE analysis could be used to study the variability of the JCV genome. The target sequence of this study was 233 bp long, within the gene coding for the VP1, known to contain several type-determining sites. Four DGGE patterns have been observed among our strains. Five strains, from African individuals, were of type 3 and exhibited the same electrophoretic pattern, clearly distinguishable from that of the type 1 strains detected in the urine from 6 European individuals. Five type 1 strains shared a similar DGGE pattern, slightly different from that of the sixth. A different pattern characterised as a type 2 strain was detected in the urine from a Peruvian individual. These results suggest that DGGE analysis could be used as a screening assay for choosing strains for nucleotide sequencing. The analysis of a fragment larger than the one used in this study could allow the identification of more types and subtypes.

Adolescent↗

The fusion protein MEN 11303 (granulocyte-macrophage colony stimulating factor/erythropoietin) acts as a potent inducer of erythropoiesis.

OBJECTIVE: A fusion protein made of human granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), referred to as MEN 11303, has been tested for biologic activity using mobilized CD34(+) cells. METHODS AND RESULTS: MEN 11303 and a combination of GM-CSF/EPO produced the same amount of colony-forming unit granulocyte-macrophage (CFU-GM), of burst-forming unit erythroid (BFU-E), and of multipotent CFU-mixed. After 15 days, liquid cultures of CD34(+) cells exposed to MEN 11303 yielded a total cell number larger than that obtained with an equimolar mixture of GM-CSF and EPO, with a clear prevalence of cells exhibiting an erythroid phenotype. A colony-forming cell assay established from CD34(+) cells precultured with MEN 11303 for 7 days yielded a greater amount of BFU-E than GM-CSF/EPO combination. Exposing CD34(+) cells to MEN 11303 for 7 days in liquid culture resulted in higher recoveries of cells expressing a comparatively less differentiated hematopoietic phenotype and of long-term culture initiating cells. A cell-based binding-competition assay using the human EPO-receptor (EPO-R) transfected murine Ba/F3EPOR cell line showed that MEN 11303 bound to EPO-R with a sixfold lower affinity but induced a more sustained receptor phosphorylation. MEN 11303 supported the growth of Ba/F3EPOR cells more efficiently than EPO and remained detectable in the spent culture medium for a longer time. CONCLUSIONS: MEN 11303 and the combination of GM-CSF/EPO are equally potent in recruiting hematopoietic progenitors into cycle, but the fusion protein is superior in promoting the expansion of committed erythroid percursors. Primitive hematopoiesis is less affected by MEN110303 than GM-CSF/EPO combination. Part of these effects may reflect the peculiar interaction of the EPO moiety of MEN 11303 with the EPO-R.

Antigens, CD34↗

Bone fracture analysis on the short rod chevron-notch specimens using the X-ray computer micro-tomography.

Mechanical fatigue of bone leads to micro-cracking which is associated with remodeling, establishing a balance in the microcrack population of the living tissue, thus, in the steady-state, the microstructure of bone provides sites of discontinuity acting as stress raisers. Hence fracture toughness plays a decisive role in bone functionality by determining the level to which the material can be stressed in the presence of cracks, or, equivalently, the magnitude of cracking which can be tolerated at a given stress level. Cortical bone, which behaves as a quasi-brittle solid when fractured, was tested as short-rod chevron-notched tension specimens (CNT). The main features of the CNT specimen are its geometry and the V shaped notch. The notch leads to steady-state crack propagation whilst the requested geometry allows a diameter 40% smaller than the thickness of a standard compact tension specimens (CT). These features are essential to distinguish the inhomogeneties in the fracture properties of materials like bone. Bone structure and crack propagation of the CNT specimens were analyzed using X-ray computed micro-tomography (XMT), which is a non-invasive imaging technique. The unique feature of the micro-CT is the high resolution three-dimensional image which consists of multi-sliced tomographs taken in a fine pitch along the rotational axis. Fracture toughness (K(IC)) computed according to the peak load was 4.8 MNm(-3/2) while that derived from experimental calibration tests using XMT was 4.9 MNm(-3/2).

Journal Article↗