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Biomedical subjects

V Bonazzi

Publications and source records attributed to V Bonazzi.

9 recordsLinked to original sources

Electrochemotherapy a novel approach to the treatment of metastatic nodules on the skin and subcutaneous tissues.

Electrochemotherapy (ECT) is a new treatment for metastatic nodules of solid tumors on the skin or subcutaneous tissue. ECT is a combination of a physical effect, cell membrane poration, and cytotoxic drug administration. Cell membrane poration is achieved by applying short intense electric filed pulses. Pore formation on the cell membrane allows low permeant drugs like bleomycin or cisplatin to enter the cell and thus locally increase their toxicity: up to 10.000 times for bleomycin and 80 times for cisplatin. ECT has been investigated in a multicenter study European Standard Operating Procedures for Electrochemotherapy (ESOPE) that demonstrates how by ECT over 80% of the cutaneous or subcutaneous metastatic nodules can be healed, thus confirming the results of previous studies. ECT efficacy is independent of tumor histology. The experience gathered in the ESOPE study allowed to prepare standard operating procedures that are key to the dissemination of the technology. ECT is safe effective, the treatment is completed in one session usually on an out-patient basis with minimum side-effects. ECT is cost-effective and, although palliative, it ameliorates patients' quality of life. ECT is the treatment of choice for tumors refractory to conventional treatment, can be used in form of cytoreductive therapy before conventional treatment for organ sparing and functions saving, finally can be adopted to treat hemorrhagic or painful nodules, it can be applied in previously irradiated areas.

Animals↗

Thyroid nodule evaluation: what have we really learned from recent clinical guidelines?

Recent guidelines for the evaluation of thyroid nodules clarify the diagnostic algorithm while also reporting important differences. The performance of fine needle aspiration (FNA) for cytological examination follows serum TSH determination and thyroid ultrasonography. Thyroid scintigraphy is recommended following a low TSH value and/or FNA yielding an indeterminate follicular cytology. The use of thyroid ultrasonography is the source of some controversy: though it is recommended as a principal first test, its real-time use to guide FNA ranges from routine to only following an FNA yielding an inadequate or nondiagnostic cytological result. In clinical practice, the proportion of physicians utilizing ultrasonography, scintigraphy and FNA varies and frequently deviates from recommended guidelines. The development of guidelines is necessary to bring about consistency and optimization to the diagnostic work-up of thyroid nodules. It is likely that novel diagnostic procedures, such as molecular markers, large needle aspiration biopsy and thyroid imaging with tracers beyond conventional radioactive iodine or (99m)Tc pertechnetate, will lead to improved performance and implementation of guidelines.

Biopsy, Fine-Needle↗

New polymers for drug delivery systems in orthopaedics: in vivo biocompatibility evaluation.

The use of biodegradable polymers for drug delivery systems excluded the need for a second operation to remove the carrier. However, the development of an avascular fibrous capsule, reducing drug release, has raised concern about these polymers in terms of tissue-implant reaction. Five novel polymers were evaluated in vivo after implantation in the rat dorsal subcutis and compared to the reference polycaprolactone (PCL). Poly(cyclohexyl-sebacate) (PCS), poly(L-lactide-b-1,5-dioxepan-2-one-b-L-lactide) (PLLA-PDXO-PLLA), two 3-hydroxybutyrate-co-3-hydroxyvalerate copolymers (D400G and D600G), and a poly(organo)phosphazene (POS-PheOEt:Imidazole) specimens were histologically evaluated in terms of the inflammatory tissue thickness and vascular density at 4 and 12 weeks from surgery. The highest values of inflammatory tissue thickness were observed in D600G (P < 0.01), PCS (P < 0.001) and PLLA-PDXO-PLLA (P < 0.001) at 4 weeks, while POP-PheOEt:Imidazole showed the lowest value of inflammatory tissue thickness (P < 0.05) at 12 weeks. D400G, D600G, PLLA-PDXO-PPLA and POP-PheOEt:Imidazole showed higher (P < 0.001) values of vascular density near the implants in comparison to PCL at 4 weeks. Finally, D400G and D600G increased their vessel densities while POP-PheOEt:Imidazole and the synthetic polyester PLLA-PDXO-PLLA presented similar vessel density values during experimental times. These different behaviours to improve neoangiogenesis without severe inflammatory tissue-responses could be further investigated with drugs in order to obtain time-programmable drug delivery systems for musculoskeletal therapy.

Animals↗

Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC).

The chemotherapeutic approach to hormone-refractory metastatic prostate cancer (MHRPC) for a long time included only estramustine. Then, attempts have been made with other various agents as cyclophosphamide, vinblastine, etoposide, taxanes and carboplatinum. Although the new drugs and combinations have increased the response rate of MHRPC, they have had no impact on the natural history of MHRPC, which is about 1 year as median time of survival. After an occasional observation of prolonged response in a patient with MHRPC treated with a very well tolerated oral low-dose of cyclophosphamide, from February 1996 to October 2002, seven more patients with MHRPC and progressive disease were consecutively recruited. Response to treatment was evaluated by conventional radiological procedures and/or serial serum PSA measurements. The decline of PSA value was considered to assess the response consistent with the response guidelines from the prostate specific antigen-working group. All eight studied patients continuously received oral low dose cyclophosphamide until progression or the occurrence of significant toxicity. So far three patients (37.5%) progressed (PD), two (25%) showed PR and the three remaining SD. Response rate was 25%, and clinical benefit occurred in 62.5% of the studied patients. In the five patients with clinical benefit on cyclophosphamide median duration of clinical benefit, PR and SD were 9, 24+ and 8 months, respectively. In these five patients median overall survival times from cyclophosphamide and from the first regimen of chemotherapy were 17 and 33+ months respectively, while in the three patients with PD they were 4 and 13 months. The same interval times in patients with > or =50% decline of serum PSA were 29 and 50.5 months, while in those with <50% decline of the same marker, they were 13 and 32 months, respectively. Grade 2 or 3 neutropenia were observed in all the studied patients. In four (50%) of them pulmonary and urinary infections that were easily cured by the common antibiotics occurred. These data suggest that the metronomic use of cyclophosphamide, given alone, has similar or higher activity with lower toxicity than when administered with other active drugs. So it can be an useful option before or after the use of other single or combined potentially active chemotherapeutic agents.

Administration, Oral↗

Biomaterials in orthopedic surgery: effects of a nickel-reduced stainless steel on in vitro proliferation and activation of human osteoblasts.

A new austenitic stainless steel compound, P558, has been widely recognized to have good mechanical properties, excellent potential for corrosion resistance and negligible nickel ion release, making it a promising substitute for more expensive metallic prostheses with limited machinable features. The effect of P558 was studied in vitro and human osteoblast- like cells (MG63) were cultured directly on P558, Ti6Al4V alloy (Ti), and polystyrene (Control) for 72 hours. Osteoblast functions were evaluated by assaying cell proliferation and synthetic activity after 1.25(OH)2D3 stimulation. Results demonstrated that growth of MG63 on P558 was not negatively affected when compared to the Ti and Control groups and showed no alteration in the production of ALP, NO and PICP. Moreover, IL-6 was lower, whereas OC and TGFbeta1 were significantly higher. SEM images revealed that cells proliferated and differentiated on P558 without any alteration in their morphology. The current findings have demonstrated that P558 promotes osteoblast proliferation, activation and differentiation without negative effects and, thus, its good biocompatibility when used for orthopedic application.

Alloys↗

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗

[The clinical aspects of 4 cases of oral Kaposi's sarcoma].

The authors report 4 cases of patients with AIDS and harbouring oral lesions of Kaposi's sarcoma. They describe the macroscopic appearance and clinical signs in relation to epidemic Kaposi's systemic ones. Because of the anamnestic or coexistence of oral mycosis (Candida), in every case the authors suppose that it may precede Kaposi's manifestations, with a very severe prognosis, correlated to progressive and deadly course of this illness.

AIDS-Related Complex↗

[Prevention of oral mucositis during antiblastic chemotherapy].

Oral complications of cancer chemotherapy have been studied in a group of 50 adult patients. A number of 25 patients was treated by means of oral hygiene and prophylactic measures: drugs and topical agents, while the other group of 25 patients had not received stomatological prevention. The goal of the research has showed that prevention measures and elimination of existing or potential sources of infection reduce and minimize mucositis, infection etc.

Aged↗

Vascular endothelial growth factor (VEGF) and other common tissue prognostic indicators in breast cancer: a case-control study.

VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p = 0.012, p = 0.007, p = 0.005, p = 0.005, p = 0.002 and p = 0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p = 0.015), while ER (p = 0.05 and p = 0.021) and MIB-1 (p = 0.031 and p = 0.022) were significant in both the N+ and N- subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.

Adult↗