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Biomedical subjects

S Cecchini

Publications and source records attributed to S Cecchini.

At least 19 recordsLinked to original sources
PubMed2012

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30&#xb1;10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Animals↗
PubMed2003

Surveillance for endometrial cancer with transvaginal ultrasonography of breast cancer patients under tamoxifen treatment.

The association of endometrial thickness with the risk of developing endometrial cancer (EC) within 2 years was investigated in a consecutive cohort of 1205 breast cancer patients under tamoxifen treatment, undergoing transvaginal ultrasonography (TVUS) for follow-up purpose (asymptomatic, 1068) or for abnormal uterine bleeding (AUB, 137). Linkage with tumour registry allowed for the follow-up of 3184.3 person-years. According to underlying incidence, 1.85 EC cases were expected in the study cohort while 12 were observed (observed/expected ratio=6.49, 95% CI 3.35-11.33; asymptomatic=4.09, 95% CI 1.65-8.43, symptomatic=35.71, 95% CI 11.59-83.34). No EC was observed with thickness (half layer) <3 mm. Raising this threshold increased specificity with a substantial loss of sensitivity (>or=3, >or=4, >or=6, >or=9 mm; spec.=25.8, 44.5, 76.1, 91.5%, sens.=100, 91.6, 75.0, 66.6%). The presence of AUB was rather specific (88.94%) but poorly sensitive (41.67%). A combination of AUB presence/absence and thickness allowed the best accuracy (AUB + thickness >or=3, >or=4 or >or=5; sens.=100, 81.6 or 91.6%; spec.=22.8, 40.4, or 56.7%). Breast cancer patients under tamoxifen might be selected for further invasive assessment on the basis of AUB and endometrial thickness assessed at TVUS.

Aged↗
PubMed2003

Clinical impact (cost-effectiveness) of qualifying atypical squamous cells of undeterminate significance (ASCUS) in cases favoring a reactive or dysplastic process.

The cost-effectiveness of qualifying ASCUS cases into two different subcategories, favoring a reactive (ASCUS-R) or dysplastic process (ASCUS-S), was evaluated at the Centro per lo Studio e la Prevenzione Oncologica of Florence in a prospective study. The study determined the positive predictive value (PPV) for histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2) or more (CIN>) severe lesion of the two ASCUS subgroups. ASCUS-S had a PPV (10.78%) comparable to low-grade squamous intraepithelial lesions (LSIL) (11.40%). For ASCUS-R cases, the recommendation of 6-mo repeat cytology prompting colposcopy in cases of persistent ASCUS or more severe cytology was also effective, as it selected a subgroup with a relatively high PPV (10.34%). The cost-effectiveness of a protocol based on ASCUS qualification was compared with two other possible options for nonqualified ASCUS cases: immediate colposcopy and colposcopy in persistent ASCUS at 6-mo repeat cytology. The detection rate of CIN2> was substantially higher using ASCUS qualification (35.9 vs 14.8 or 17.1). The cost per ASCUS subject was euro 24.99, 27.11, or 25.14 and that per CIN2> detected was euro 697, 1,831 or 1,470 for the three options, respectively. The evidence that ASCUS detection option implies a higher detection rate of CIN2> and subsequently a lower cost per CIN2> detection must be considered with caution and deserves confirmation by other comparative studies.

Cervix Uteri↗
PubMed2002

Alteration of protein structure induced by low-energy (<18 eV) electrons. I. The peptide and disulfide bridges.

We present measurements of low-energy (<18 eV) electron-stimulated desorption of anions from acetamide (CH(3)CONH(2)) and dimethyl disulfide [DMDS: (CH(3)S)(2)] films. Electron irradiation of physisorbed CH(3)CONH(2) produces H(-), CH(3)(-) and O(-) anions, whereas the H(-), CH(2)(-), CH(3)(-), S(-), SH(-) and SCH(3)(-) anions are observed to desorb from the DMDS film. Below 12 eV, the dependence of the anion yields on the incident electron energy exhibits structures that indicate that a resonant process (i.e. dissociative electron attachment) is responsible for molecular fragmentation. Within the range of 1-18 eV, it is found that (1.7 and 1.4) x 10(7) H(-) ions/incident electron and (7.8 x 10(-11) and 4.3 x 10(-8)) of the other ions/incident electron are desorbed from acetamide and DMDS films, respectively. These results suggest that, within proteins, the disulfide bond is more sensitive to low-energy electron attack than the peptide bond. In biological cells, some proteins interact closely with nucleic acid. Therefore, the observed fragments, when produced from secondary low-energy electrons generated by high-energy radiation, not only may denature proteins, but may also induce reactions with the nearby nucleic acid and damage DNA.

Acetamides↗
PubMed1997

Radon measurements in the Gran Sasso Underground Laboratory.

Systematic radon monitoring in the Gran Sasso Underground Laboratory was performed in order to determine the background radon contribution to the sophisticated experimental apparatus and to check health physics standards for the personnel. As expected, the radon concentrations were found to depend strongly on the ventilation in the three experimental halls. Considerable reductions in the radon concentrations were obtained in 1993, when fresh air was drawn into the laboratory through a pipe and exhaust air was routed into the highway tunnel.

Air Pollutants, Radioactive↗
PubMed1996

Screening by ultrasonography for endometrial carcinoma in postmenopausal breast cancer patients under adjuvant tamoxifen.

Seven-hundred thirty-seven asymptomatic postmenopausal breast cancer patients under long-term adjuvant tamoxifen therapy (average, 50 months) were screened by endometrial ultrasonography. Abnormal endometrial thickness (6 mm or larger) was observed in 209 subjects and was significantly associated with patients' age and duration of tamoxifen therapy. Outpatient endometrial biopsy was recommended in presence of abnormal endometrial thickness: 25 subjects refused biopsy, whereas 76 were not biopsied because of cervical stenosis and were followed-up by repeat sonography. Of 108 biopsied subjects, one case of endometrial carcinoma (as expected in the screened cohort according to age-specific incidence rates provided by the regional cancer registry) and one case of endometrial hyperplasia were histologically confirmed, whereas endometrial atrophy was evident in the remaining cases. No other case of endometrial carcinoma has been recorded so far in the studied cohort according to the local cancer registry and no further change of the endometrium has been observed at sonographic follow-up. The cohort will be followed-up by repeat annual endometrial sonography. Thus far, we did not find evidence of increased prevalence of endometrial pathology (carcinoma or hyperplasia) which may be ascribed to tamoxifen therapy. The apparent increase in endometrial thickness observed at sonography might be explained by tamoxifen-induced changes of endometrial stroma and myometrium, misinterpreted as hyperplasia, while causing no real epithelial disease.

Aging↗
PubMed1995

Trends in cervical cancer incidence in the district of Florence.

The trend in cervical cancer incidence in the District of Florence from 1975 to 1989 was investigated. Tuscany Cancer Registry data were available since 1985. Incidence data from 1975 to 1985 were obtained through a retrospective survey of all the Departments of Pathology and Gynaecology in the district. Cytological screening for cervical cancer has been available in the district since 1973, and since 1980 active invitation of residents aged 25 to 59 years has been in use. A significant trend in decreasing incidence was evident for the overall population (P = 0.003) and for 40-49 (P = 0.028), 50-59 (P < 0.001) and 60-69 (P = 0.002) year age groups, whereas no significant trend was observed for the age group 30-39 years. An association between attendance to screening and reduced incidence was evident, in that a greater reduction was evident for those cohorts (ages 50-59 and 60-69) who had a higher compliance to screening 10-15 years before. If the decrease in cervical cancer incidence was spontaneous, a parallel decrease of CIN3, which is commonly assumed to be the precursor of invasive carcinoma, would be expected. On the contrary, the detection rate of CIN3 at first Pap test showed a significant increase in the study period. All these findings suggest that the observed reduction in cervical cancer incidence was mostly due to the effect of screening, and stress the need for optimising the coverage of the invited population.

Adult↗
PubMed1993

Screening history of incident cases of invasive carcinoma of the cervix. Florence district 1988-1989.

BACKGROUND: Incidence cases of carcinoma of the cervix may be assumed as failures of a population-based cytologic screening program. Monitoring such cases would provide an estimate of screening effectiveness, and evaluating the causes of the failures would improve screening performance. STUDY DESIGN: All incident cases of cervicocarcinoma registered in 1988 and 1989 in the Tuscany Tumor Registry were eligible for the study and were reviewed. RESULTS: Sixty-nine eligible cases were considered. Non- or irregular attendance (negative smear-to-diagnosis interval > 5 years) for the Pap smear was recorded in 53 subjects. A false-negative smear (smear-to-diagnosis interval < 5 years) and refused or inadequate assessment/treatment at private practices or local hospitals were recorded in 12 cases. False-negative smears by the local screening program were recorded in 4 cases only. CONCLUSIONS: Non- or irregular attendance was the major cause of screening failures. Since cytologic screening or diagnostic assessment outside the screening program may be inadequate, central screening and follow-up is recommended. Non-attenders showed a strong negative attitude towards screening, and general practitioners and gynecologists need to be further stimulated for systematic screening promotion. Immediate evaluation of the screening history of incident cases of cervicocarcinoma should be mandatory in any screening program.

Adult↗
PubMed1993

Testing cervicography and cervicoscopy as screening tests for cervical cancer.

AIMS AND BACKGROUND: Suboptimal sensitivity is currently reported for Pap test in screening for cervical cancer. Colposcopy is known to be more sensitive than cytology but its use as a screening test is not possible due to costs and complexity. Screening by cervicography has been suggested as a compromise being less costly and feasible. The present study evaluates the feasibility of screening by cervicography and cervicoscopy (naked eye examination of the cervix after acetic acid lavage) on a consecutive screening series. METHODS: Cervicography and cervicoscopy were performed by the smear taker in subjects consecutively attending a screening clinic. Women with abnormal cytology (atypia or more severe lesion) and/or abnormal cervicography or cervicoscopy (acetowhite lesion) underwent colposcopic assessment. The three screening methods were compared according to positivity rate, CIN 2-3 detection rate and positive predictive value. RESULTS: 2105 consecutive subjects were screened. Positivity rate was 3.8%, 15.3% or 25.4% for cytology, cervicography or cervicoscopy, respectively, 486 of 555 women attended the assessment phase, 281 directed biopsies were performed and 8 CIN 2-3 lesions were detected. Cytology, cervicography and cervicoscopy, detected 5.5, or 7 of 8 CIN 2-3 lesions, respectively. The positive predictive value was 0% for cytologic atypia, 25% for cytologic SIL, 1.75% for cervicography and 2.05% for cervicoscopy. Detecting one CIN 2-3 lesion at cytology cost $5,543. The cost per each additional cytologically negative CIN 2-3 lesion detected at cervicography or cervicoscopy was $12,947 or $3,916, respectively. CONCLUSIONS: The study confirms the limited sensitivity of cytology for CIN 2-3. The association of cervicography was not cost effective. Cervicoscopy was poorly specific but increased the detection rate of CIN 2-3 at relatively low costs. Cervicoscopy is worth further evaluation as a screening test.

Adolescent↗