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Biomedical subjects

E Paci

Publications and source records attributed to E Paci.

At least 37 records · Page 2Linked to original sources
PubMed2002

Time trends in cancer incidence and mortality in central Italy.

Time trends in cancer incidence and mortality represent an essential tool for monitoring the changes in population lifestyle and in the environmental risks and the effectiveness of the health system on cancer control in a specific area. During 1985-1997 82 506 malignant tumours were diagnosed in the Tuscany Cancer Registry, central Italy (about 1 200 000 inhabitants) and 54 979 cancer deaths registered in the period 1985-1999 by the Regional Mortality Registry were analysed. A statistically significant decrease in incidence was evidenced for stomach and gallbladder in both sexes, and for oesophagus, larynx and lung among males. Significant increases were documented for melanomas of the skin, kidney and non-Hodgkin's lymphoma in both sexes for colon, prostate and Kaposi's sarcoma among males and for breast, thyroid and multiple myeloma among females. Mortality decreased significantly for stomach and thyroid in both sexes and for oral cavity and pharynx, oesophagus, rectum, larynx, lung, bone, prostate, testis and Hodgkin's disease among males and colon, gallbladder and breast among females. Mortality increased for soft tissue, brain and multiple myeloma. In conclusion, most of these data can be explained as the effect of the modifications that occurred in smoking habits between the sexes and as the consequence of the primary and secondary prevention activities that are ongoing in the area.

Adolescent↗
PubMed2002

Informing patients about risks and complications of anaesthesia.

BACKGROUND: This study examines the quality of patients' informed consent in patients undergoing minor surgical procedure. Information provided on risks and complications inherent in anaesthesia-care and patients' awareness of specific risks involved in anaesthesia were recorded, and the influence of a questionnaire-form was evaluated. METHODS: This is a prospective controlled study. In the first part (Group I: n=71) social and demographic data, complications and risks communicated to the patient in the preanaesthetic evaluation, as well as patients' satisfaction with the information obtained, were noted. In the second part of the study (Group II: n=201) patients were also asked to answer a questionnaire form concerning their own state of health and their knowledge of risks in anaesthesia. The statistical analysis was conducted using Pearson's Chi square test or t test, and by fitting suitable logistic models. RESULTS: The frequency of the communication of at least one of the risks and complications of anaesthesia has been 43.7% in GI and 59,7% in GII, p=0.019. Patients in class ASA III were informed more (77%, c.i. 59-90) as compared to those in class ASA I-II (52%, c.i. 45-59) (p=0.008); 37% in class ASA I-II and 65% in class ASA III desire the presence of one of their relatives during the preassessment (p=0.016). CONCLUSIONS: Our results indicate that most patients are glad to be informed, even if they are unaware of the risks and complications of anaesthesia. The questionnaire form seems to be an important tool for patient education. Ethical questions are proposed.

Anesthesia↗
PubMed2001

Forces and energetics of hapten-antibody dissociation: a biased molecular dynamics simulation study.

The unbinding of fluorescein from the single-chain Fv fragment of the 4D5Flu antibody is investigated by biased molecular dynamics with an implicit solvation model. To obtain statistically meaningful results, a large number of unbinding trajectories are calculated; they involve a total simulation time of more than 200 ns. Simulations are carried out with a time-dependent perturbation and in the presence of a constant force. The two techniques, which provide complementary information, induce unbinding by favoring an increase in the distance between the ligand and the antibody. This distance is an appropriate progress variable for the dissociation reaction and permits direct comparison of the unbinding forces in the simulations with data from atomic force microscopy (AFM). The time-dependent perturbation generates unfolding pathways that are close to equilibrium and can be used to reconstruct the mean force; i.e. the derivative of the potential of mean force, along the reaction coordinate. This is supported by an analysis of the overall unbinding profile and the magnitude of the mean force, which are similar to those of the unbinding force (i.e. the external force due to the time-dependent perturbation) averaged over several unbinding events. The multiple simulations show that unbinding proceeds along a rather well-defined pathway for a broad range of effective pulling speeds. Initially, there is a distortion of the protein localized in the C-terminal region followed by the fluorescein exit from the binding site. This occurs in steps that involve breaking of specific electrostatic and van der Waals interactions. It appears that the simulations do not explore the same barriers as those measured in the AFM experiments because of the much higher unfolding speed in the former. The dependence of the force on the logarithm of the loading rate is linear and the slope is higher than in the AFM, in agreement with experiment in other systems, where different slopes were observed for different regimes. Based on the unbinding events, mutations in the 4D5Flu antigen binding site are predicted to result in significant changes in the unbinding force.

Animals↗
PubMed2001

Measuring interval cancers in population-based screening using different assays of fecal occult blood testing: the District of Florence experience.

The fecal occult blood test (FOBT) has demonstrated its efficacy in reducing mortality from colorectal cancer (CRC). The guaiac-based FOBT has been criticized for its low sensitivity. In this study, two different assays for FOBT (guaiac or an immunochemical test based on reversed passive hemagglutination [RPHA]) were tested for comparison within a population-based screening program for colorectal cancer in the province of Florence (Italy). The proportional incidence method was used to calculate sensitivity for both FOBTs, according to rank of screening (first or repeat), age at entry (two groups of 50 to 59 and 60 to 70 years old) and lesion site (colon or rectum). When comparing FOBTs, the sensitivity multivariate Poisson regression was used to adjust for other variables. The sensitivity after the first 2 years was 50% (95% confidence interval [CI] 34% to 63%) for the guaiac test versus 82% (95% CI 67% to 92%) for RPHA. At multivariate analysis the risk of developing an interval cancer after a guaiac test is almost 3 times that after RPHA (rate ratio = 2.64; 95% CI 1.3 to 5.4). Our study confirms that RPHA is more sensitive than the guaiac test. The assumption that FOBT screening for CRC has to be based on a guaiac test should be reconsidered, and RPHA should be recommended as the standard FOBT for screening purposes.

Aged↗
PubMed2001

Exploration of partially unfolded states of human alpha-lactalbumin by molecular dynamics simulation.

Molecular dynamics simulations are used to probe the properties of non-native states of the protein human alpha-lactalbumin (human alpha-LA) with a detailed atomistic model in an implicit aqueous solvent environment. To sample the conformational space, a biasing force is introduced that increases the radius of gyration relative to the native state and generates a large number of low-energy conformers that differ in terms of their root-mean-square deviation, for a given radius of gyration. The resulting structures are relaxed by unbiased simulations and used as models of the molten globule and partly denatured states of human alpha-LA, based on measured radii of gyration obtained from nuclear magnetic resonance experiments. The ensembles of structures agree in their overall properties with experimental data available for the human alpha-LA molten globule and its more denatured states. In particular, the simulation results show that the native-like fold of the alpha-domain is preserved in the molten globule. Further, a considerable proportion of the antiparallel beta-strand in the beta-domain are present. This indicates that the lack of hydrogen exchange protection found experimentally for the beta-domain is due to rearrangement of the beta-sheet involving transient populations of non-native beta-structures. The simulations also provide details concerning the ensemble of structures that contribute as the molten globule unfolds and shows, in accord with experimental data, that unfolding is not cooperative; i.e. the various structural elements do not unfold simultaneously.

Binding Sites↗
PubMed2001

Three key residues form a critical contact network in a protein folding transition state.

Determining how a protein folds is a central problem in structural biology. The rate of folding of many proteins is determined by the transition state, so that a knowledge of its structure is essential for understanding the protein folding reaction. Here we use mutation measurements--which determine the role of individual residues in stabilizing the transition state--as restraints in a Monte Carlo sampling procedure to determine the ensemble of structures that make up the transition state. We apply this approach to the experimental data for the 98-residue protein acylphosphatase, and obtain a transition-state ensemble with the native-state topology and an average root-mean-square deviation of 6 A from the native structure. Although about 20 residues with small positional fluctuations form the structural core of this transition state, the native-like contact network of only three of these residues is sufficient to determine the overall fold of the protein. This result reveals how a nucleation mechanism involving a small number of key residues can lead to folding of a polypeptide chain to its unique native-state structure.

Acid Anhydride Hydrolases↗
PubMed2001

Quality of life assessment and outcome of palliative care.

Quality of life (QoL) assessment is crucial for the evaluation of palliative care outcome. In this paper, our methodological approach was based on the creation of summary measures. Fifty-eight Palliative Care Units (PCUs) in Italy participated in the study. Each PCU randomly selected patients to be 'evaluated' among the consecutively 'registered' patients. At baseline (first visit) and each week the patient was asked to fill in a QoL questionnaire, the Therapy Impact Questionnaire (TIQ). Short-survivors (<7 days) were not included in the QoL study. The random sample of patients (n = 601) was highly representative of the general patient population cared for by the PCUs in Italy. The median survival was 37.9 days. We collected 3546 TIQ, 71.4 % completed by the patients. A Summary Measure Outcome score was calculated for 409 patients (81% of the patients included in the QoL study). The results of this national study showed that cooperative clinical research in palliative care is possible and QoL measures can be used to assess the outcome.

Aged↗
PubMed2001

Trends in breast cancer mortality, incidence, and survival, and mammographic screening in Tuscany, Italy.

OBJECTIVE: The study describes breast cancer mortality trends in Tuscany (period 1970-97), comparing Florence with the rest of Tuscany (Florence excluded), and, for Florence, incidence (period 1985-94) and survival (1985-86 versus 1991-92) trends, taking into account the diffusion of screening. METHODS: Mortality and incidence rates, age-adjusted on the European population, and 95% confidence intervals (95% CI). Five-year relative survival rates and estimates of risk of dying provided by the Cox model. RESULTS: Mammographic screening, started at the beginning of the 1970s in some municipalities, largely involved the Florence area after 1990 (mammograms/years: from 8,000-9,000 to 28,000-29,000, respectively, before and after 1990). In the same period no population-based screenings were ongoing in the rest of Tuscany. A significant mortality drop was observed in Tuscany (-3.7%/year), starting at the beginning of the 1990s and observed for ages < or = 74 (especially ages 40-49: -11.2%/year). The drop was similar in Florence and in the rest of Tuscany. In ages 50-69, incidence, increasing between 1985-87 and 1988-90 (+6.5%), rose sharply in 1991-94 (+17.0%); it was stable in other ages. Local disease increased more markedly in ages 50-69 (globally: +88.3%), but also in other ages (+20-30%). Regional and metastatic cancers decreased. A significantly better 5-year survival was observed among cases diagnosed in 1991-92, persisting after adjustment by extent of disease. CONCLUSION: Even if the causes of breast cancer mortality trends are not easy to clarify in an observational study. our data suggest that the drop in mortality observed in Tuscany at the beginning of the 1990s could be largely explained by both earlier detection, outside of an organized screening program, and by better treatments. The increase in incidence and the shift in stage distribution that occurred before the enlargement of the screening area and in age groups not involved in the program, supports the role of a 'spontaneous' widespread earlier detection. The better survival of the period 1991-92, only partly explained by the shift in stage at diagnosis, indirectly supports the role of improvement in therapy.

Adult↗
PubMed2001

Incidence of second cancers among women with in situ carcinoma of the breast.

A population-based cohort of 371 women with carcinoma in situ (CIS) of the breast, collected by the Tuscany Cancer Registry, has been analysed for further invasive cancers. All cases, diagnosed between 1985 and 1997, have been followed up to the end of 1997. During 1707 person-years of follow-up, 27 further invasive cancers were diagnosed while 13.7 were expected (Observed/Expected=2.0, P<0.05). The relative risk for invasive breast cancers was 3.7 (P<0.05). According to the surgical treatment for CIS and the site of further invasive breast cancer, no side specific difference was evident. No significant increase was evident for other cancer sites; only non-melanomatous skin cancers occurred more frequently than expected (O/E=4.2). The cumulative risk of developing an invasive cancer after CIS was 13.2% at 10 years. There were also two deaths due to breast cancer (O/E=8.3; P<0.05) corresponding to a cumulative mortality risk of 2% at 10 years. We have quantified the risk of developing an invasive breast cancer among women with CIS of the breast as four times that of the general population.

Journal Article↗
PubMed2001

An application of the two-source capture-recapture method to estimate the completeness of the Tuscany Cancer Registry, Italy.

The purpose of this study was to apply a two-way capture-recapture method to estimate the Tuscany Cancer Registry completeness, taking into account the presence of dependence between sources. Cases incident during 1995-1996 were flagged according to three sources of information: clinical notes, pathological reports and death certificates. For each group of cases notified by one source the dependence between the other two has been quantified and the completeness has been estimated by a two-way capture-recapture method. When only two (or substantially two) sources are dependent on each other it is possible to correct for it by pooling the two sources in a single group and comparing it with the remainder source by a two-way capture-recapture method. The capture-recapture method has been applied to the overall 12 387 incident cases and to 1569 female breast and 1443 lung cancer cases. After correction for the greatest dependence among the three couples of sources of information, the estimates of completeness were 97.4% for the whole case series, 88.7% for female breast and 99.6% for lung cancer. With the limit of multiple strong dependence between sources, the two-way capture-recapture method seems a simple and useful tool for estimating the completeness of cancer registration.

Female↗
PubMed2001

The impact of screening and early diagnosis on survival--results from the Italian cancer registries.

Early diagnosis of neoplastic diseases enjoined large popularity in the last two decades. In many countries or European regions, population-based cancer screening programs for breast, cervical and colorectal cancer are going on. Diagnostic tests, like the PSA test for prostate cancer, are not yet validated in terms of their efficacy in reducing specific mortality, but their spontaneous diffusion is changing the pattern of the disease incidence. In this contribution, we discuss briefly the survival trends for some tumours (breast, cervix, colorectal, melanoma and prostate cancer) for which the occurrence rates are modified by screening and for some of them we evaluate the possible impact of early diagnosis on survival rates.

Aged↗
PubMed2000

Unfolding proteins by external forces and temperature: the importance of topology and energetics.

Unfolding of proteins by forced stretching with atomic force microscopy or laser tweezer experiments complements more classical techniques using chemical denaturants or temperature. Forced unfolding is of particular interest for proteins that are under mechanical stress in their biological function. For beta-sandwich proteins (a fibronectin type III and an immunoglobulin domain), both of which appear in the muscle protein titin, the results of stretching simulations show important differences from temperature-induced unfolding, but there are common features that point to the existence of folding cores. Intermediates detected by comparing unfolding with a biasing perturbation and a constant pulling force are not evident in temperature-induced unfolding. For an alpha-helical domain (alpha-spectrin), which forms part of the cytoskeleton, there is little commonality in the pathways from unfolding induced by stretching and temperature. Comparison of the forced unfolding of the two beta-sandwich proteins and two alpha-helical proteins (the alpha-spectrin domain and an acyl-coenzyme A-binding protein) highlights important differences within and between protein classes that are related to the folding topologies and the relative stability of the various structural elements.

Protein Folding↗
PubMed2000

Regression of multiple hepatic masses in a young patient with thalassaemia.

BACKGROUND: We report a young girl with thalassaemia who showed development and regression of multiple hepatic masses. RESULTS: The tumours, detected 3 years after allogeneic bone-marrow transplantation, showed progressive reduction in size and number following a phlebotomy program to treat iron overload. CONCLUSION: The detailed CT, MRI and histological findings are described.

Bone Marrow Transplantation↗
PubMed1999

Forced unfolding of fibronectin type 3 modules: an analysis by biased molecular dynamics simulations.

Titin, an important constituent of vertebrate muscles, is a protein of the order of a micrometer in length in the folded state. Atomic force microscopy and laser tweezer experiments have been used to stretch titin molecules to more than ten times their folded lengths. To explain the observed relation between force and extension, it has been suggested that the immunoglobulin and fibronectin domains unfold one at a time in an all-or-none fashion. We use molecular dynamics simulations to study the forced unfolding of two different fibronectin type 3 domains (the ninth, 9Fn3, and the tenth, 10Fn3, from human fibronectin) and of their heterodimer of known structure. An external biasing potential on the N to C distance is employed and the protein is treated in the polar hydrogen representation with an implicit solvation model. The latter provides an adiabatic solvent response, which is important for the nanosecond unfolding simulation method used here. A series of simulations is performed for each system to obtain meaningful results. The two different fibronectin domains are shown to unfold in the same way along two possible pathways. These involve the partial separation of the "beta-sandwich", an essential structural element, and the unfolding of the individual sheets in a stepwise fashion. The biasing potential results are confirmed by constant force unfolding simulations. For the two connected domains, there is complete unfolding of one domain (9Fn3) before major unfolding of the second domain (10Fn3). Comparison of different models for the potential energy function demonstrates that the dominant cohesive element in both proteins is due to the attractive van der Waals interactions; electrostatic interactions play a structural role but appear to make only a small contribution to the stabilization of the domains, in agreement with other studies of beta-sheet stability. The unfolding forces found in the simulations are of the order of those observed experimentally, even though the speed of the former is more than six orders of magnitude greater than that used in the latter.

Dimerization↗