Study of the radionuclide deposition in the radioactive ion line of the Selective Production of Exotic Species (SPES) facility.

SPES (Selective Production of Exotic Species) is a second generation facility for the production of radioactive ion beams that is going to be commissioned at the Laboratori Nazionali di Legnaro of INFN at Legnaro, Padua, Italy. Radioactive neutron-rich isotopes are expected to be produced by nuclear fission induced by a 40 MeV, 200 µA primary proton beam impinging on a 238UCx target. The expected reaction rate is about 1013 fission/s. Radioactive ion beams are produced using the isotope separation on-line technique. The production of such an amount of radioactive species raises radiological issues throughout the life cycle of the facility. A study of the radioactive contamination of the components of the radioactive ion beam line is performed with the FLUKA Monte Carlo simulation code, under realistic hypotheses for the produced isobaric beams. The present results complete previous studies focused on the radiological impact of the production target irradiation, the residual activation of the primary proton beam line and the radioactive contamination of the ion source complex. The overall ambient dose equivalent rate due to the different radiation sources is calculated at several positions inside the production bunker and at different times after a typical one-year operating period of the facility with the 238UCx target at full power. The obtained results and the developed methodology provide the guidelines and the needed tools to plan ordinary and extraordinary interventions as well as final decommissioning of the SPES facility.

New solid state laser system for SPES: Selective Production of Exotic Species project at Laboratori Nazionali di Legnaro.

The Selective Production of Exotic Species project is under construction at Laboratori Nazionali di Legnaro-INFN. The aim of the collaboration is to produce highly pure Radioactive Ion Beams (RIBs) from fission fragments of a uranium carbide (UCx) target activated by a cyclotron proton beam. In order to select a specific atomic species, the main tool to be applied is the resonant laser ionization technique. We have just completed the installation of a dedicated all solid state laser system whose elements are tunable to transitions of all the elements/isotopes of interest for the project. The new laser system is based on three Titanium:sapphire laser sources, independently pumped by three Nd:YLF pump lasers, and it can be coupled to two high harmonic generation (second harmonic generation, third harmonic generation, and fourth harmonic generation) setups. The power, wavelength, and position of the laser beams are continuously monitored and stabilized by using automated active systems to improve the beam production stability of RIBs. This paper presents the main features of the laser system and examples of application of a laser ion source, including a first demonstration of photoionization of stable silver, one of the most requested elements for RIB application.

Study of the radioactive contamination of the ion source complex in the Selective Production of Exotic Species (SPES) facility.

The Isotope Separation On-Line (ISOL) technique is today established as one of the primary methods to produce high-intensity and high-quality radioactive beams. This technique produces, for a given amount of the desired isotope, many orders of magnitude of other radioactive species. Due to the activation generated by interactions of the primary beam, intense neutron fields, and deposition of the produced radioactive ions inside beam line elements, an ISOL facility in operation becomes an intense radioactive source. Therefore, the biological hazard imposes severe radiological safety challenges to the design, operation, maintenance, and final decommissioning of such facilities. A challenging component is the ion source complex, where the ion extraction electrode provides the extraction of radioactive ions from the ion source and the first acceleration to the extracted beam. The radioactive contamination of this sub-component is studied, by means of the FLUKA code, in the case of the Selective Production of Exotic Species facility, which is in the advanced construction phase at Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Legnaro, Padua, Italy. The developed model includes isotope production by the interactions of a 40 MeV energy proton beam on a 238UCx target, selection of radioactive isotopes that are able to stick on the electrode tip, time evolution of the deposited isotopes during the operation and cooling periods before maintenance interventions, and evaluation of the ambient dose equivalent rate generated by the contamination of the electrode tip. Based on these results, the possibility of manual interventions for maintenance and emergency vs the use of remote handling systems is discussed.

Radiation resistance of elastomeric O-rings in mixed neutron and gamma fields: Testing methodology and experimental results.

Materials and components employed in the presence of intense neutron and gamma fields are expected to absorb high dose levels that may induce deep modifications of their physical and mechanical properties, possibly causing loss of their function. A protocol for irradiating elastomeric materials in reactor mixed neutron and gamma fields and for testing the evolution of their main mechanical and physical properties with absorbed dose has been developed. Four elastomeric compounds used for vacuum O-rings, one fluoroelastomer polymer (FPM) based and three ethylene propylene diene monomer rubber (EPDM) based, presently available on the market have been selected for the test. One EPDM is rated as radiation resistant in gamma fields, while the other elastomers are general purpose products. Particular care has been devoted to dosimetry calculations, since absorbed dose in neutron fields, unlike pure gamma fields, is strongly dependent on the material composition and, in particular, on the hydrogen content. The products have been tested up to about 2 MGy absorbed dose. The FPM based elastomer, in spite of its lower dose absorption in fast neutron fields, features the largest variations of properties, with a dramatic increase in stiffness and brittleness. Out of the three EPDM based compounds, one shows large and rapid changes in the main mechanical properties, whereas the other two feature more stable behaviors. The performance of the EPDM rated as radiation resistant in pure gamma fields does not appear significantly better than that of the standard product. The predictive capability of the accelerated irradiation tests performed as well as the applicable concepts of threshold of radiation damage is discussed in view of the use of the examined products in the selective production of exotic species facility, now under construction at the Legnaro National Laboratories of the Italian Istituto Nazionale di Fisica Nucleare. It results that a careful account of dose rate effects and oxygen penetration in the material, both during test irradiations and in operating conditions, is needed to obtain reliable predictions.

A preliminary study for the production of high specific activity radionuclides for nuclear medicine obtained with the isotope separation on line technique.

Radiopharmaceuticals represent a fundamental tool for nuclear medicine procedures, both for diagnostic and therapeutic purposes. The present work aims to explore the Isotope Separation On-Line (ISOL) technique for the production of carrier-free radionuclides for nuclear medicine at SPES, a nuclear physics facility under construction at INFN-LNL. Stable ion beams of strontium, yttrium and iodine were produced using the SPES test bench (Front-End) to simulate the production of 89Sr, 90Y, 125I and 131I and collected with good efficiency on suitable targets.

Photo-ionization of aluminum in a hot cavity for the selective production of exotic species project.

SPES (Selective Production of Exotic Species) is an Isotope Separation On-Line (ISOL) based accelerator facility that will be built in the Legnaro-Istituto Nazionale di Fisica Nucleare (INFN) Laboratory (Italy), intended to provide intense neutron-rich radioactive ion beams obtained by proton-induced fission of a uranium carbide (UCx) target. Besides this main target material, silicon carbide (SiC) will be the first to be used to deliver p-rich beams. This target will also validate the functionality of the SPES facility with aluminum beam as result of impinging SiC target with proton beam. In the past, off line studies on laser photoionization of aluminum have been performed in Pavia Spectroscopy Laboratory and in Laboratori Nazionali di Legnaro; a XeCl excimer laser was installed in order to test the laser ionization in the SPES hot cavity. With the new Wien filter installed a better characterization of the ionization process in terms of efficiency was performed and results are discussed.

Ongoing characterization of the forced electron beam induced arc discharge ion source for the selective production of exotic species facility.

An intense research and development activity to finalize the design of the target ion source system for the selective production of exotic species (SPES) facility (operating according to the isotope separation on line technique) is at present ongoing at Legnaro National Laboratories. In particular, the characterization of ion sources in terms of ionization efficiency and transversal emittance is currently in progress, and a preliminary set of data is already available. In this work, the off-line ionization efficiency and emittance measurements for the SPES forced electron beam induced arc discharge ion source in the case of a stable Ar beam are presented in detail.

Off-line ionization tests using the surface and the plasma ion sources of the SPES project.

The development of new target ion source systems for the selective production of exotic species (SPES) facility is currently in progress at Legnaro National Laboratories. In this context, the study of ion sources and their performance in terms of ionization efficiency and transversal emittance is a crucial point in order to maximize the available yields, particularly for short-lived isotopes. In this work, preliminary off-line ionization efficiency and emittance measurements for the SPES surface and plasma ion sources are presented. The plasma source emittance measurements are supported by dedicated numerical calculations.

Studies for aluminum photoionization in hot cavity for the selective production of exotic species project.

Selective production of exotic species (SPES) is an ISOL-based accelerator facility that will be built in the Legnaro INFN Laboratory (Italy), intended to provide an intense neutron-rich radioactive ion beams obtained by proton induced fission of an uranium carbide target. Beside this main target, a silicon carbide (SiC) target will the first to be used to deliver some p-rich beams. This target will validate also the functionality of the SPES facility with aluminum beam as result of hitting SiC target with protons. In the past off-line studies on laser photoionization of aluminum have performed in Pavia Spectroscopy Laboratory and in Laboratori Nazionali di Legnaro where, recently, a XeCl excimer laser was installed in order to test the laser ionization in the SPES hot cavity. Results are promising to justify further studies with this technique, aiming a better characterization of the SPES ion extraction capability under laser photoionization.

Expression and localization of the deubiquitinating enzyme mUBPy in wobbler mouse testis during spermiogenesis.

Mouse ubiquitin-specific processing protease (mUBPy) is a deubiquitinating enzyme highly expressed in both brain and testis. In testis, it interacts with the DnaJ protein, MSJ-1; both mUBPy and MSJ-1 are located on the cytoplasmic surface of the developing acrosome and in the centrosomal region during spemiogenesis. Present data show the first appearance in testis of mUbpy mRNA and protein at 10 days post-partum (d.p.p.). In addition, to investigate on a possible role of mUBPy in sperm formation, we took advantage of mutant wr/wr (wobbler) mice characterized by male infertility, which is likely due to the lack of a real, functional acrosome. RT-PCR and Northern blot analyses show that mUbpy is up-regulated in adult wobbler testis. Furthermore, in wild-type testis mUBPy protein is primarily detected by Western blot in the soluble (cytosolic/nuclear) fraction during the first round of spermatogenesis and in the adult. By contrast, mUBPy is primarily detected in membranous/insoluble protein fraction when wobbler phenotype is clearly shown (30 d.p.p.) and in adult wobbler testis. By immunohistochemistry, whereas in wild-type animals mUBPy marks the profile of the acrosomic vesicle in differentiating spermatids, in wobbler mice only a detergent pre-treatment procedure allows to detect mUBPy immunoreactivity, which results in diffuse spotted granules inside the cytoplasm and around the nuclear shape. In conclusion, in wobbler testis expression of mUbpy is up-regulated, while a differential sorting of the protein characterizes wobbler spermatids where acrosome formation is impaired.

Structure of msj-1 gene in mice and humans: a possible role in the regulation of male reproduction.

Msj-1 gene encodes a DnaJ protein highly expressed in spermatids and spermatozoa of both rodents and amphibians, possibly involved in vesicle fusion and protein quality control by means of interaction with heat shock proteins. We isolated and characterized the entire murine msj-1 gene and searched for putative msj-1-like genes into the human genome. Furthermore, ultrastructural localization of MSJ-1 was analyzed in mouse germ cells by immunogold electron microscopy. The analysis of murine msj-1 genomic sequence reveals that it is an intron less gene. Putative promoter region was predicted within the 600 bp upstream the transcription start site. In mouse, msj-1 maps on chromosome 1, into an intronic region of UDP glucuronosyl-transferase 1 family cluster. At ultrastructural level, MSJ-1 marks the developing acrosomic vesicle and the sperm centriolar region. A blast search against the human genome database revealed two closed regions (Ha and Hb) on human chromosome 2 having high nucleotide identity with murine msj-1 coding region. Similarly to mouse, in human both regions map into an intronic region of UDP glycosyl-transferase 1 family polypeptide A cluster (ugt1a@). A significant ORF encoding a putative DnaJ protein of 145 aa was predicted from Ha. Finally, expression analysis, conducted by RT-PCR in human sperm cells, demonstrated that Ha mRNA is effectively present in humans; by Western blot, a specific MSJ-1 band of approximately 30kDa was detected in human sperm. Taken together, these data suggest that msj-1 gene might be conserved among vertebrates and might exert fundamental functions in reproduction.

Learning curve for translaryngeal tracheotomy in head and neck surgery.

OBJECTIVES: Translaryngeal tracheotomy (TLT) is a widely accepted procedure in intensive-care units for its simplicity of execution, low morbidity, rapid wound closure after cannula removal, good esthetic results, and lack of long-term sequelae. The aim of this study was to evaluate the feasibility and use of adopting TLT in patients with cancer undergoing major head and neck surgery. STUDY DESIGN: Prospective analysis of learning curve and incidence of complications in 41 patients with cancer who underwent TLT at the Division of Head and Neck Surgery of the European Institute of Oncology from November 1997 to June 1999. METHODS: Patient characteristics, pathology, anatomic characteristics of the neck, and surgical short-term and long-term complications were noted. The patients were divided into consecutive groups of six or seven patients, and time trends in occurrence of complications and time to execute the procedure were assessed. RESULTS: TLT performance time decreased from 50 minutes in the first seven patients to 24 minutes in the last group. The technique was easy to perform and safe, with only two minor complications during surgery. However, minor complications occurred in three and major complications in 17 patients in the days immediately following surgery, almost entirely attributable to lack of counter-cannula and stylet. CONCLUSIONS: In view of the high proportion of major complications, TLT using the presently available kit is unsuitable for major head and neck surgery. However, the considerable advantages of the technique would recommend it as a valid alternative to surgical tracheotomy if the kit included a counter-cannula and stylet.

Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series.

BACKGROUND: Axillary lymph node dissection is an established component of the surgical treatment of breast cancer, and is an important procedure in cancer staging; however, it is associated with unpleasant side effects. We have investigated a radioactive tracer-guided procedure that facilitates identification, removal, and pathologic examination of the sentinel lymph node (i.e., the lymph node first receiving lymphatic fluid from the area of the breast containing the tumor) to predict the status of the axilla and to assess the safety of foregoing axillary dissection if the sentinel lymph node shows no involvement. METHODS: We injected 5-10 MBq of 99mTc-labeled colloidal particles of human albumin peritumorally in 376 consecutive patients with breast cancer who were enrolled at the European Institute of Oncology during the period from March 1996 through March 1998. The sentinel lymph node in each case was visualized by lymphoscintigraphy, and its general location was marked on the overlying skin. During breast surgery, the sentinel lymph node was identified for removal by monitoring the acoustic signal from a hand-held gamma ray-detecting probe. Total axillary dissection was then carried out. The pathologic status of the sentinel lymph node was compared with that of the whole axilla. RESULTS: The sentinel lymph node was identified in 371 (98.7%) of the 376 patients and accurately predicted the state of the axilla in 359 (95.5%) of the patients, with 12 false-negative findings (6.7%; 95% confidence interval = 3.5%-11.4%) among a total of 180 patients with positive axillary lymph nodes. CONCLUSIONS: Sentinel lymph node biopsy using a gamma ray-detecting probe allows staging of the axilla with high accuracy in patients with primary breast cancer. A randomized trial is necessary to determine whether axillary dissection may be avoided in those patients with an uninvolved sentinel lymph node.

Long-term, totally implantable central venous access ports connected to a Groshong catheter for chemotherapy of solid tumours: experience from 178 cases using a single type of device.

The aim of this study was to examine the early and late complications rate of central venous access ports connected to the Groshong catheter for long-term chemotherapy delivering. All patients suffering from a neoplastic disease, who required long-term chemotherapy and underwent insertion of implantable ports during a 21-month period (1 October 1994-30 June 1996) were prospectively studied. A single type of port was used, constructed of titanium and silicone rubber (Dome Port, Bard Inc., Salt Lake City, U.S.A), connected to an 8 F silastic Groshong catheter tubing (Bard Inc.). A team of different operators (two general surgeons, one interventional radiologist and four anaesthesiologists) was involved in inserting the port. All devices were placed in the operating room under fluoroscopic control. A central venous access form was filled in by the operator after the procedure and all ports were followed prospectively for device-related and overall complications. Data from the follow-up of these patients were entered in the form and collected in a database. Follow-up continued until the device was removed, the patient died or the study was closed. 178 devices, comprising a total of 32,089 days in situ, were placed in 175 patients. Three patients received a second device after removal of the first. Adequate follow-up was obtained in all cases (median 180 days, range 4-559). 138 devices (77.5%) were still in situ when the study was closed. Early complications included six pneumothoraxes, three arterial punctures and two revisions for port and/or catheter malfunction (overall early complications in 8 patients). Late complications included 3 cases (1.68% of devices) of catheter rupture and embolisation (0.093 episodes/1000 days of use), 2 cases (1.12% of devices) of venous thrombosis (0.062 episodes/1000 days of use), 1 case (0.56% of devices) of pocket infection (0.031 episodes/1000 days of use), and 4 cases (2.24% of devices) of port-related bacteraemias (0.124 episodes/1000 days of use). Infections were caused by coagulase-negative Staphylococcus aureus (4 cases) and Bacillus subtilis (1 case); they required port removal in 3 out of 5 cases. This study represents the largest published series of patients with totally implantable access ports connected to Groshong catheters; this device is a good option for long-term access to central veins and delivery of chemotherapeutic regimens, including continuous intravenous infusions. The low incidence of major complications related to implantation and management of these devices support increased use in oncology patients.

Subclavian venous thrombosis due to indwelling catheters: a prospective study on 52 patients.

Clinical occurrence of subclavian venous thrombosis due to indwelling catheters is rare, but there is some evidence that subclinical thrombosis frequently occurs. It is purpose of this study to report the results of a prospective investigation in patients with subclavian vein catheters. Fifty-two patients admitted to the Istituto Nazionale Tumori of Milan and candidate to infraclavicular percutaneous catheterization of the subclavian vein were evaluated. There were 26 polyvinyl chloride and 26 rubber silicone catheters, which were correctly positioned in the superior vena cava-atrium. Average duration of the intravenous stay was 12.8 days. Asymptomatic thrombosis was venographically demonstrated in 46.1% of the polyvinyl chloride catheters and in 11.5% of the silicone ones (p = 0.005). The average age of catheters with or without thrombosis was 10.8 and 13.8 days, respectively. Addition of heparin to the infusate (1 U/ml) did not reduce the thrombosis rate in polyvinyl chloride or in silicone catheters, but risk of thrombosis was significantly higher (p = 0.03) in polyvinyl chloride catheters without heparin in comparison to the silicone ones. Osmolarity of the infusional fluid, manipulation during the cannulation, colonization of the catheter tip, and duration of the intravenous stay of the catheter apparently did not influence the rate of thrombosis. Since the natural history of the thrombotic subclavian veins is not known, some caution must be paid to repeat the percutaneous cannulation of the same vein and the change the catheter over a guidewire.

Prevention and treatment of central venous catheter sepsis by exchange via a guidewire. A prospective controlled trial.

A new approach for preventing and treating sepsis due to central venous catheter (CVC) has been devised at the Istituto Nazionale Tumori of Milan. A prospective protocol has been developed that includes the weekly exchange of the CVC via a guidewire as well as its exchange when a CVC-related sepsis is suspected. Growth of microorganisms on the tip of the CVC is defined as contamination if peripheral blood culture is negative and as sepsis if it is positive for the same microorganism. Colonization simply means growth of microorganism independently of the results of peripheral blood culture. Two hundred seven CVCs (64 polyvinyl chloride and 143 rubber silicone) were evaluated in 62 patients, for a total of 170 exchanges. The incidence of colonization and sepsis was 33.8% and 4.8%, respectively, a rate which is not significantly different from the values found in 81 historical controls (30.8% and 11.1%). However, it is noteworthy that the sepsis rate was reduced strongly during the first month of observation (0% vs. 11.9%; p = 0.01), whereas in the second month, it was similar in both groups (15% vs. 7.1%). Moreover, it should be noted that three-fourths of the colonized CVCs became negative after the first exchange, and virtually all were negative at the fourth exchange. All of the episodes of sepsis resolved spontaneously with the CVC exchange. The study, therefore, concludes that this procedure: 1) is without risk for CVC cross contamination, 2) is effective in the treatment of contaminated CVCs and of septic patients without any interruption of total parenteral nutrition, and 3) can reduce the incidence of CVC sepsis during the first month of total parenteral nutrition. One must be cautious about the possible onset of pulmonary embolism in patients with subclavian venous thrombosis, since a transient pulmonary embolism occurred in one of the patients. With the use of silastic CVCs, which are less thrombogenic than polyvinyl ones, the rate of pulmonary embolism due to blind exchange (without previous venography) is estimated to be 0.1% to 0.2%.

Impact of cancer, type, site, stage and treatment on the nutritional status of patients.

This study analyzed the nutritional status of cancer patients in relation to type and site of origin of the tumor, stage of disease, and previous chemical or radiation therapy. The analysis was performed on 321 patients (280 with cancer and 41 controls). The nutritional parameters included per cent of weight loss, anthropometric indices (arm circumference, triceps skinfold, arm muscle circumference), creatinine-height index, serum protein, albumin, total iron binding capacity and cholinesterase, C3 and C4 components of complement, total peripheral lymphocytes, and skin tests. The statistical comparison between patients with different tumors and controls, between patients with different stages of the same tumor, and between patients treated with or without previous chemical or radiation therapy led to the following conclusions: 1) malnutrition is mainly related to the type and site of origin of the tumor and, in the early stages of disease, is more pronounced in patients with cancer of the esophagus and stomach; 2) except in patients with breast and cervix cancer, malnutrition gets more severe as the disease becomes advanced; 3) chemical or radiation therapy has a variable impact on the nutritional status, but in selected patients it causes a drop in body weight, arm circumference, arm muscle circumference, and peripheral lymphocytes; 4) body weight, cutaneous delayed hypersensitivity and serum albumin are the most commonly altered parameters.

Pathogenesis and predictability of central venous catheter sepsis.

The purposes of this study were to analyze the causes and routes of infection of indwelling central venous catheters and to improve the diagnosis of catheter sepsis before the removal of the cannula. One hundred forty catheter tips were prospectively studies; also, cultures of 52 proximal segments of catheters, 44 swabs of the subcutaneous segment, 195 skin entry sites, 181 infusional fluids, 208 blood samples, and 106 infected distant sites were examined. The catheter sepsis rate was 7.6%, but this sepsis was primary in only 3.4%, because in 4.2% prior isolation of organisms from the wound, urine, throat, or sputum was possible, indicating that the catheter was not primarily responsible for the infection. Primary infection always disappears with removal of the cannula (with or without antibiotics), whereas the course of the secondary infection is related to the gravity of the infected foci and the involved microorganisms. Contamination of the infusional fluid, the skin entry site, and some distant foci carry a real risk of seeding the catheter (from 5.8% to 19.5%). The cultures of the skin entry sites, infusional fluids, distant foci, and the subcutaneous segment of the catheter did not prove useful in predicting the infection. Only the blood cultures were a reliable diagnostic tool: a positive blood culture meant colonization of the catheter tip in 44% of cases and sepsis in 36%. Although the potential colonization varied greatly for different microorganisms, the growth of microorganisms in the blood was a strong indication for removing the cannula.