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Biomedical subjects

M Ragusa

Publications and source records attributed to M Ragusa.

13 recordsLinked to original sources
PubMed2006

Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy.

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

Apoptosis↗
PubMed2003

AntiClustal: Multiple Sequence Alignment by antipole clustering and linear approximate 1-median computation.

In this paper we present a new Multiple Sequence Alignment (MSA) algorithm called AntiClusAl. The method makes use of the commonly use idea of aligning homologous sequences belonging to classes generated by some clustering algorithm, and then continue the alignment process ina bottom-up way along a suitable tree structure. The final result is then read at the root of the tree. Multiple sequence alignment in each cluster makes use of the progressive alignment with the 1-median (center) of the cluster. The 1-median of set S of sequences is the element of S which minimizes the average distance from any other sequence in S. Its exact computation requires quadratic time. The basic idea of our proposed algorithm is to make use of a simple and natural algorithmic technique based on randomized tournaments which has been successfully applied to large size search problems in general metric spaces. In particular a clustering algorithm called Antipole tree and an approximate linear 1-median computation are used. Our algorithm compared with Clustal W, a widely used tool to MSA, shows a better running time results with fully comparable alignment quality. A successful biological application showing high aminoacid conservation during evolution of Xenopus laevis SOD2 is also cited.

Algorithms↗
PubMed2000

The role of silicone stents in the treatment of cicatricial tracheal stenoses.

OBJECTIVE: Tracheal stenting for cicatricial stenoses is reserved for patients whose lesions are deemed inoperable for local or general reasons. The aim of our study was to verify the long-term results of silicone tracheal stents in such a clinical setting. METHODS: Clinical data of 45 patients treated by tracheal silicone stents, between 1987 and 1999, were reviewed. All patients had highly symptomatic cicatricial stenoses; they were selected for stenting rather than for surgery because of local and general conditions. This series has been divided in two groups according to the purpose of stenting: bridge to surgery or definitive treatment. Follow-up ranged between 12 and 83 months. Twenty-seven patients received a Montgomery T tube (Hood Laboratories, Pembroke, Mass), 16 a Dumon stent (Novatech, Plan de Gras, France), and 2 a Dynamic stent (Rusch, Kernen, Germany). RESULTS: No procedure-related mortality was observed. Nine patients underwent curative resection and reconstruction after a variable stenting period; one had a recurrent stenosis and was treated for palliation with a T tube. Tracheal stenting was performed for palliation as a definitive treatment in 37 patients. Among this group, 11 patients died of unrelated causes at a median of 10 months after the endoscopic treatment. The stent was permanently removed in 10 after a median interval of 32 months (range 9-70 months); in 4 others, symptomatic recurrence of the stenosis was observed within 6 weeks of stent removal. None of the patients successfully decannulated had a completely normal tracheal lumen but all remained asymptomatic because the residual stenosis was mild or well tolerated for concomitant limitation of physical activity. CONCLUSIONS: Long-term treatment with a silicone stent was safe and well tolerated in cicatricial tracheal stenoses. This procedure can be considered as a bridge to curative surgery or as a definitive treatment. The latter, generally performed for palliation, may provide satisfactory therapeutic results in selected patients, even in the presence of severe circumferential stenoses.

Adolescent↗
PubMed2000

[Central venous access systems in the oncologic patient].

BACKGROUND: A safe and dependable venous access is mandatory in order to perform cancer chemotherapy and monitor blood values in the neoplastic patient. Prolonged infusions of medications with sclerosing action may damage the vessel wall, inducing chemical thrombophlebitis. Furthermore, extravasation of necrotizing compounds may be a danger to the patient. The application of totally implantable venous access systems (VAS) started in 1982, in the United States of America, where at present 500,000 devices are implanted annually. In Italy such method has been introduced in a later period, with a constantly growing trend. VAS devices have evolved since their first presentation, and so have application techniques: the original surgical route has been supported by the percutaneous one, considered most appropriate by several Centers. In this study, personal experience concerning application of VAS in cancer patients is presented. METHODS: From July 1994 to February 1998, at the General Thoracic Surgery Dept. of the University of Perugia, 198 VAS have been implanted in 195 patients. During the first period all the systems have been applied by surgical cutdown of the cephalic vein (150 cases). In the last 12 month the percutaneous technique for vein puncture has been adopted in 48 patients. RESULTS: Immediate and late complications have occurred: among the former, pneumothorax, hematoma, malposition; among the latter, infection, subclavian vein thrombosis, catheter rupture. The results are analysed after an extensive review of the international literature; pros and cons of the different implantation techniques and the technical aspects useful for preventing complications are underlined.

Adult↗
PubMed1996

Spatial expression of alpha and beta tubulin genes in the late embryogenesis of the sea urchin Paracentrotus lividus.

In Paracentrotus lividus sea urchin embryos, at blastula stage, there is an abrupt increase in the abundance of alpha and beta tubulin transcripts in particular of the PI beta 1, PI beta 2 and PI alpha 2 forms. In order to assign specific functions to the various embryonic tubulin genes, we have used whole-mount in situ hybridization to determine spatial patterns of expression of five different alpha and beta tubulin embryonic genes. The PI beta 3 transcripts, as previously shown for PI alpha 2, start to localize in a few founder cells from which the neurogenic territory differentiates. The other four embryonic tubulin mRNAs (PI beta 1/2 and PI alpha 1/10), are localized in the ciliated band- and gut-territory. These territories originate by morphogenetic processes, which occur in late embryogenesis in the sea urchin and depend on cellular interactions. In particular, the interactions between the oral and aboral ectoderm specify the position of the ciliated band, whereas the invagination of the vegetal plate forms the gut territory. We suppose that the increase in alpha and beta tubulin transcripts could be functionally related to these two morphogenetic events. Our results show in fact that specific tubulin isotypes, or a mix of them, are expressed in and mark the ciliated band and the neighboring oral/aboral ectoderm cells of the ciliated band, in addition to the cells of the gut territory. The same localization of all these tubulin transcripts has been confirmed by whole-mount in situ hybridization experiments performed on embryos treated with agents able to induce deciliation or exogastrulation. Furthermore a putative correlation of PI beta 2 with cilium formation has been shown by the results obtained on deciliated embryos.

Animals↗
PubMed1995

Alpha-tubulin marker gene of neural territory of sea urchin embryos detected by whole-mount in situ hybridization.

We have used Northern blot and whole-mount in situ hybridizations to analyze the temporal and spatial expression pattern of the Pl alpha 2 alpha-tubulin gene in Paracentrotus lividus sea urchin embryos. The Pl alpha 2 transcript is first detectable at 14 h post-fertilization (blastula stage) and it is only expressed in the oral ectoderm. The amount of transcripts of this gene increases throughout development and accumulates up to the pluteus stage. In this stage the Pl alpha 2 transcript is localized in the neural structures of the embryo. We conclude that the Pl alpha 2 gene is an early neurogenic territory marker. Furthermore we have observed the same localization of the Pl alpha 2 transcript in the Zn(++)- or phenytoin-treated embryos, confirming the animal localization of the Pl alpha 2 transcript and its specific relation to neurogenic territory, whose differentiation starts from few founder cells present at blastula stage.

Amino Acid Sequence↗
PubMed1992

Chest wall stabilization with synthetic reabsorbable material.

Experimental results and preliminary clinical experience with synthetic reabsorbable materials in chest wall reconstruction are reported. Six beagle dogs underwent chest wall resection involving three or four consecutive ribs. Reparative procedure was performed by construction of a polydioxanone-band grid, anchored to the adjacent undamaged ribs. A mild wound infection developed in 1 animal but resolved without rejection of the prosthesis. The experimental material has shown favorable properties, both mechanical and biological. Subsequently, 11 patients, with different indications, underwent reconstructive procedures of the chest wall with reabsorbable prostheses. No complications have occurred. Long-term stability was excellent in all patients, with a mean follow-up longer than 6 months. The advantages of reabsorbable compounds are pointed out along with the possible applications for chest wall reconstruction after chest wall resection.

Absorption↗
PubMed1991

[Picotamide: use in chronic obliterative arteriopathies of the lower limbs].

In the present study the authors evaluated treatment efficiency and patient compliance of medium-term therapy with Picotamide, given in doses of 900 mg/die for the first 15 days, and 600 mg/die up to the completion of a three-month period, to 50 patients affected by vaso-occlusive arterial disease of the lower limbs. At follow-up visits the following controls have been carried out: CW Doppler sonography of the lower limbs, Maximum Walking Distance (M.W.D.), Red blood cell count, White blood cell count, Platelet count, Haemoglobin and Fibrinogen levels. At the end of the three-month therapy period the Ankle-Arm parameters remained unchanged.

Aged↗
PubMed1984

Microsurgical approach to pancreatic duct occlusion in the pig by means of a prolamine solution.

Prolamine is an alcoholic solution of zein, with the property of polymerizing within 15 minutes in a humid medium. Such a substance has been injected in the pancreatic duct of 10 pigs with a microsurgical technique, causing complete occlusion. The prolamine gel produces a progressive fibrosclerosis of the exocrine pancreatic parenchyma, sparing the endocrine portion. The resulting pancreatic atrophy avoids the occurrence of inflammatory complications that often hamper surgery on such gland. The 10 pigs under study showed post-operative normal values of blood glucose and insulin, and a decrease in serum alpha-amylase levels. Complications occurred in only one case, and the microscopic pattern was similar in all cases. Microsurgical approach and use of prolamine are considered effective both in pancreatic transplantation and in chronic pancreatitis.

Animals↗
PubMedDate not supplied

[Surgical treatment of thyroid cancer in 243 cases].

The incidence of thyroid cancer, which accounts for 1-2% of all malignancies, constantly increasing. Its management requires an integrated approach, in which the surgeon plays a pivotal role, providing the basis for further treatment. At present, the extent of exeresis, the lymph-node dissection technique and the management of upper respiratory-digestive tract infiltration are still debatable issues. The authors report on their experience with 243 surgically treated thyroid malignancies over the period from January 1986 to December 1999. The operations performed were: total thyroidectomy 226 cases, lobo-isthmectomy 3 cases, total thyroidectomy + lung metastasectomy 1 case, total thyroidectomy + SE quadrantectomy 1 case, total thyroidectomy + monolateral modified neck dissection 30 cases, total thyroidectomy + bilateral modified neck dissection 17 cases, total thyroidectomy + radical neck dissection 1 case, total thyroidectomy + tracheal sleeve resection 5 cases. In 9 cases, extensive tracheal involvement (5.5 cm), age or neoplastic histology allowed only palliative treatment (endoscopic recanalization + tracheal endoprosthesis or tracheostomy. Nd-Yag laser endoscopic recanalization was performed in 2 patients as a preliminary stage in subsegmental radical treatment, and in 5 cases for palliation. Recurrent laryngeal nerve palsy occurred in 3 cases, long-term hoarseness in 2, and hypoparathyroidism in 4. The overall mean hospital stay was 4.8 days. Of 299 patients still alive, 215 are free of disease. Surgery is the treatment of choice, with the goal of completely removing the neoplasm, together with any anatomical structures involved in infiltration (muscles, respiratory-digestive tract, lymph nodes). Satisfactory palliation can be achieved by endoprosthesis deployment or tracheostomy in all cases where surgery is ruled out due to extent of disease, patient age or histological type.

Adult↗
PubMedDate not supplied

[Surgery of pulmonary and hepatic metastases].

In recent years surgery for hepatic and pulmonary metastases has been undertaken with a curative intent in a growing percentage of cases. In the present study the Authors evaluate their own experience in such a field, and summarize the state of the art, as it appears from a review of the international literature. At present, the subject is not settled, as several aspects are matter of debate (prognostic significance of free interval, tumor doubling time, number and location of metastatic lesions, histologic type, and stage, of the primary tumor, approach to synchronous metastases, accuracy of preoperative diagnosis), with different therapeutic implications according to the hepatic or pulmonary site. Pulmonary metastases should be managed by resection through a median sternotomy, in order to allow thorough exploration of both lungs. Hepatic lesions (from colorectal primaries) should be resected with a free margin not less than 1-2 cm. The need for uniformity of selection criteria and for the establishment of protocols including adjuvant therapy is strongly felt.

Adult↗