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Biomedical subjects

A Ferrari

Publications and source records attributed to A Ferrari.

At least 91 records · Page 5Linked to original sources
PubMed2001

A Monte Carlo code for a direct estimation of radiation risk.

An example of pragmatic approach for predicting mixed field effects is presented. The method was initially applied adopting the following, commonly used, assumptions: a) radiation risk (typically cancer) is correlated with chromosome aberration induction; b) radiation-induced chromosome-exchange yield can be well described by a linear-quadratic dependence on particle fluences (mostly linear with high-LET radiation), with parameters depending on particle types and energies. Information on monochromatic field radiobiological effects was integrated in a condensed-history Monte Carlo transport code (FLUKA), able to simulate nuclear interactions. The integrated code provides the chromosome aberration yield (and thus an estimation of radiation risk) in each voxel of any irradiated volume, given any external mixed-field irradiation; in the present work, the method was tested for neutron irradiation of a water phantom. FLUKA was then coupled with a geometrical human phantom provided with different radiation shielding, in order to apply this approach to estimate radiation risk in manned space missions.

Chromosome Aberrations↗
PubMed2001

A reference radiation facility for dosimetry at flight altitude and in space.

A reference facility for the intercomparison of active and passive detectors in high-energy neutron fields is available at CERN since 1993. A positive charged hadron beam (a mixture of protons and pions) with momentum of 120 GeV/c hits a copper target, 50 cm thick and 7 cm in diameter. The secondary particles produced in the interaction are filtered by a shielding of either 80 cm of concrete or 40 cm of iron. Behind the iron shielding, the resulting neutron spectrum has a maximum at about 1 MeV, with an additional high-energy component. Behind the concrete shielding, the neutron spectrum has a pronounced maximum at about 70 MeV and resembles the high-energy component of the radiation field created by cosmic rays at commercial flight altitudes. The facility is used for a variety of investigations with active and passive neutron dosimeters. Its use for measurements related to the space programme is discussed.

Altitude↗
PubMed2001

The FLUKA radiation transport code and its use for space problems.

FLUKA is a multiparticle transport code capable of handling hadronic and electromagnetic showers up to very high energies (100 TeV), widely used for radioprotection and detector simulation studies. The physical models embedded into FLUKA are briefly described and their capabilities demonstrated against available experimental data. The complete modelling of cosmic ray showers in the earth atmosphere with FLUKA is also described, and its relevance for benchmarking the code for space-like environments discussed. Finally, the ongoing developments of the physical models of the code are presented and discussed.

Aerospace Medicine↗
PubMed2001

Development of a space radiation Monte Carlo computer simulation based on the FLUKA and ROOT codes.

This NASA funded project is proceeding to develop a Monte Carlo-based computer simulation of the radiation environment in space. With actual funding only initially in place at the end of May 2000, the study is still in the early stage of development. The general tasks have been identified and personnel have been selected. The code to be assembled will be based upon two major existing software packages. The radiation transport simulation will be accomplished by updating the FLUKA Monte Carlo program, and the user interface will employ the ROOT software being developed at CERN. The end-product will be a Monte Carlo-based code which will complement the existing analytic codes such as BRYNTRN/HZETRN presently used by NASA to evaluate the effects of radiation shielding in space. The planned code will possess the ability to evaluate the radiation environment for spacecraft and habitats in Earth orbit, in interplanetary space, on the lunar surface, or on a planetary surface such as Mars. Furthermore, it will be useful in the design and analysis of experiments such as ACCESS (Advanced Cosmic-ray Composition Experiment for Space Station), which is an Office of Space Science payload currently under evaluation for deployment on the International Space Station (ISS). FLUKA will be significantly improved and tailored for use in simulating space radiation in four ways. First, the additional physics not presently within the code that is necessary to simulate the problems of interest, namely the heavy ion inelastic processes, will be incorporated. Second, the internal geometry package will be replaced with one that will substantially increase the calculation speed as well as simplify the data input task. Third, default incident flux packages that include all of the different space radiation sources of interest will be included. Finally, the user interface and internal data structure will be melded together with ROOT, the object-oriented data analysis infrastructure system. Beyond the benefits of 'objectivity', ROOT's incorporation will also provide a graphical user interface with powerful tools for input prior to the calculation, as well as for data analysis and visualization of the results.

Computer Simulation↗
PubMed2000

Immature human NT2 cells grafted into mouse brain differentiate into neuronal and glial cell types.

NT2 cells are a transfectable human embryonal carcinoma cell line, that can be differentiated into postmitotic neuron-like cells (NT2N cells), and transplanted into rodent brains. Differentiation requires a 5-week-long treatment with retinoic acid prior to transplantation. Here, we show that this step can be omitted, and that undifferentiated NT2 cells migrate over long distances and differentiate into both neuron- and oligodendrocyte-like cell types upon grafting into brains of immunocompetent newborn mice. Grafted cells can be traced by fluorogold, with no evidence for tumor formation. Our approach provides an experimental model system which allows the immunohistological and biochemical study of neuronal and glial differentiation of human cells in vivo, and which may be suitable as an in vivo model for pharmacological studies.

Animals↗
PubMed2000

Novel 7-substituted camptothecins with potent antitumor activity.

The natural alkaloid camptothecin is the lead compound of a new class of antitumor agents with a unique mechanism of action (i.e. inhibition of DNA topoisomerase I). The pharmacological interest of these agents has generated a large number of derivatives and analogues endowed with potent cytotoxic activity, two of them being in clinical use as antitumor drugs. We have synthesized a new series of camptothecins substituted in position 7 with an alkyl or alkenyl chain bearing cyano and/or carbethoxy groups. These compounds showed potent cytotoxic activity in vitro against the human non-small-cell lung carcinoma H460 cell line, most of them exhibiting IC(50) values in the 0.05-1 microM range, more active than topotecan used as a reference compound. In particular 7-cyano-20S-camptothecin (5a) showed high in vitro cytotoxicity against a topotecan-resistant H460 cell subline (H460/TPT) and a cisplatin-resistant ovarian carcinoma subline (IGROV-1/Pt 1). In an in vivo evaluation of the antitumor activity, 5a appeared significantly more effective than topotecan in the H460 tumor model and comparable with topotecan in a small-cell lung carcinoma model and a colon carcinoma model. The efficacy and good tolerability of this compound increase interest for further preclinical development.

Animals↗
PubMed2000

Result of liver resection as treatment for metastases from noncolorectal cancer.

BACKGROUND AND OBJECTIVES: While liver resection for metastatic disease from colorectal cancer extends survival in selected patients, the efficacy of hepatectomy for metastases from other malignancies has not been defined. METHODS: Between 1988 and 1998, 20 hepatic resections were performed in 18 patients (2 underwent a double resection due to recurrence) as treatment of noncolorectal metastases. One-, 2-, and 5-year overall and disease-related actuarial survival rates were calculated. RESULTS: No intraoperative or early postoperative deaths were reported. Seven minor (30%) and 1 major (5%) postoperative complications occurred; mean blood loss was 401 +/- 324 ml. In 25% of patients, intra- or postoperative blood transfusion was needed. The mean postoperative hospital stay was 13. 2 days (range 9-23). The overall actuarial survival rate was 54% at 1 year, 42% at 2 years, and 21% at 5 years (mean 38 +/- 11 months). Survival is related to the primary tumor nature. CONCLUSIONS: Hepatic resection for metastases from noncolorectal carcinoma is safe and feasible, with a relatively low incidence of intra- or postoperative complications and a short hospital stay. Although it achieves good results in terms of survival in patients suffering from neuroendocrine metastases, it could also have a cytoreductive effect for other tumors.

Breast Neoplasms↗
PubMed2000

Prevention of early postmenopausal bone loss with cyclical etidronate.

Cyclical etidronate has been shown to be effective in the treatment of established postmenopausal osteoporosis but less is known about its effects on early menopausal bone loss. The aim of the study was to establish the effects of cyclic etidronate therapy on spinal and proximal femoral bone mineral loss in early postmenopausal women. One hundred and seven women who were within 6 months to 3 years of the menopause were recruited into a 2-year, randomised, placebo-controlled, double-blind trial. Spinal bone mineral density was within 2 SD of the age-matched mean reference value at baseline. Bone mineral density in the lumbar spine and proximal femur was assessed by dual energy X-ray absorptiometry at baseline and thereafter at 6 monthly intervals for 2 years. Urinary collagen cross-links (deoxypyridinoline and pyridinoline) were measured at the same time points. Seventy-seven women completed the study. At the end of the treatment period, the mean bone mineral density change from baseline in the treated group was +0.14% and -0.06% in the lumbar spine and femoral neck, respectively, compared to -1.49 and -2.22 in the control group. Overall, there was a significant difference between the two groups at both these sites (p=0.01 and 0.001, respectively). No significant differences between the groups were demonstrated at the greater trochanter or Ward's triangle. The conclusion was that cyclical etidronate therapy prevents bone loss in the spine and femoral neck in early postmenopausal women. It provides a safe and effective therapeutic option for the prevention of postmenopausal osteoporosis in women who are unwilling or unable to tolerate hormone replacement therapy.

Absorptiometry, Photon↗
PubMed2000

Hospitalization for peptic ulcer bleeding: evaluation of a risk scoring system in clinical practice.

BACKGROUND: Upper gastrointestinal tract haemorrhage is a common cause of hospitalization: resource utilization in management of peptic ulcer bleeding varies considerably with no apparent effect on patient outcome. Several risk score systems based on endoscopic and clinical data have been proposed and validated in order to aid patient management. AIM: To assess clinical reliability of a scoring system and to define guidelines to improve efficiency of patient management without reducing efficacy METHODS: We considered all patients admitted to our unit for bleeding peptic ulcer over a one-year period. Every patient had an early endoscopy (within 12 hours) and therapy according to the appearance of the ulcer defined by Forrest classification. All subjects were classified into low-, intermediate- and high-risk patients on basis of clinical and endoscopic features according to "Cedar Sinai Medical Center predictive index" which was applied retrospectively in first six months then perspectively for the last period using the results obtained from first semester. For each risk group, we compared Length of Hospital Stay number of blood units used in transfusion, rebleeding rate, need for surgery as well as mortality in the two periods, using Student t test. We correlated Length of Hospital Stay and every score parameter by applying analysis of variance to results over the one-year period. RESULTS: Study population consists of 91 patients. Recurrent bleeding was observed in only three entering the high-risk group, only one of whom needed surgery Overall mortality was 9.8% (9 patients, only one for rebleeding). Variance analysis showed that the only parameter of the "Cedar Sinai Medical Center predictive index" which correlated with Length of Hospital Stay was comorbidity (p < or =0.05). Comparing the two periods, a close application of the score in the last six months allowed Length of Hospital Stay to be reduced in low-risk patients (t test with p=0.004) resulting in early discharge of 33% of cases without affecting patient outcome. CONCLUSIONS: This study confirms the reliability of the "Cedar Sinai Medical Center predictive index" in clinical practice improving the strategy of applying economic resources. Longer Length of Hospital Stay of intermediate- and high-risk groups is influenced more by comorbidities than by endoscopic findings. Early discharge was possible in one third of low risk patients. An accurate evaluation clinical para meters on admission together with early endoscopy may achieve the goal of reducing costs with a correct patient management.

Adult↗
PubMed2000

Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare malignant tumor and little is known about its clinical features and management. We report on a series of 19 pediatric patients managed over 20 years. PATIENTS AND METHODS: Primary conservative surgery was performed in all patients and was radical in nine, non-radical in three; seven patients underwent biopsy alone (3 unresectable tumors, 4 metastatic disease). In two cases radical surgery was performed after primary chemotherapy. Radiotherapy was delivered to 8 patients, chemotherapy to 15. RESULTS: After a median follow-up of 74 months, the five-year survival was 80% for the whole series, 91% for patients with localized disease, 100% for patients with tumor < or = 5 cm, and 31% for those > 5 cm; 16 of 19 patients were alive (12 of 12 with grossly-resected tumor in first continuous remission). Chemotherapy achieved two partial remission among seven evaluable patients. CONCLUSIONS: Pediatric ASPS has a more favorable prognosis than its adult counterpart. In this series, tumor size correlates with metastatic disease at onset and is the major factor influencing survival. Surgery is the mainstay of therapy. The effectiveness of adjuvant therapy remains to be established, though radiotherapy may be advisable in cases of inadequate surgery.

Adolescent↗
PubMed2000

Dermoscopic features of cutaneous local recurrent melanoma.

We describe for the first time the dermoscopic features of cutaneous recurrent melanoma including a globular pattern and a diffuse nonhomogeneous pigmentation. These findings greatly differ from those observed in primary cutaneous melanoma and should be considered in the dermoscopic differential diagnosis of pigmented skin lesions.

Adult↗
PubMed2000

Central white scarlike patch: a dermatoscopic clue for the diagnosis of dermatofibroma.

In this study, dermatoscopic examination of 24 dermatofibromas was performed to evaluate specific dermoscopic criteria. A central white scarlike patch was appreciable in 22 of 24 lesions, whereas 20 of 24 dermatofibromas exhibited a delicate pigment network at the periphery. This stereotypical dermatoscopic finding allowed the diagnosis of dermatofibroma in most instances. (J Am Acad Dermatol 2000;43:1123-5.).

Adult↗
PubMed2000

In vivo analysis of wild-type and FTDP-17 tau transgenic mice.

Mutations in the coding and intronic regions of the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Some of these mutations lead to an overproduction of tau isoforms with four microtubule-binding repeats, followed by the development of fibrillary lesions and selective cell death. In order to analyze the development of these neurofibrillary lesions in transgenic mice, the longest four-repeat human brain tau isoform was expressed under control of two different neuron-specific promoters. In a first model, utilizing the human Thy1 promoter, transgenic tau was hyperphosphorylated and abnormally localized to cell bodies and dendrites. In a second model, which made use of a human Thy1.2 expression vector, transgenic expression levels were much higher, and an additional phenotype was observed: Large numbers of pathologically enlarged axons containing neurofilament- and tau-immunoreactive spheroids were present, especially in spinal cord. Signs of Wallerian degeneration and neurogenic muscle atrophy were observed. Behaviorally, transgenic mice showed signs of muscle weakness. Our data show that overexpression of human four-repeat tau in itself is sufficient to lead to nerve cell dysfunction and amyotrophy. We have now extended our initial studies by introducing exonic mutations including G2t 2V and PS01L into the tau gene in order to achieve a more advanced FTDP-17 associated phenotype.

Animals↗
PubMed2000

Teledermoscopy--results of a multicentre study on 43 pigmented skin lesions.

We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.

Adolescent↗
PubMed2000

The enhanced green fluorescent protein as a tool for the analysis of protein dynamics and localization: local fluorescence study at the single-molecule level.

The green fluorescent protein (GFP) has emerged, in recent years, as a powerful reporter molecule for monitoring gene expression, protein localization and protein-protein interaction. Several mutant variants are now available differing in absorption, emission spectra and quantum yield. Here we present a detailed study of the fluorescence properties of the Phe-64-->Leu, Ser-65-->Thr mutant down to the single molecule level in order to assess its use in quantitative fluorescence microscopy and single-protein trafficking. This enhanced GFP (EGFP) is being used extensively as it offers higher-intensity emission after blue-light excitation with respect to wild-type GFP. By means of fluorescence spectroscopy we demonstrate the absence of the neutral form of the chromophore and the lack of photobleaching recovery after ultraviolet light irradiation. Furthermore, we show that the EGFP spectral properties from isolated to densely packed molecules are highly conserved. From these experiments EGFP emerges as an ideal molecule for quantitative studies of intra and intercellular tagged-protein dynamics and fluorescence-activated cell sorting, but not for monitoring single-protein trafficking over extended periods of time.

Base Sequence↗