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Biomedical subjects

G Paoli

Publications and source records attributed to G Paoli.

At least 19 recordsLinked to original sources

Peopling of three Mediterranean islands (Corsica, Sardinia, and Sicily) inferred by Y-chromosome biallelic variability.

An informative set of biallelic polymorphisms was used to study the structure of Y-chromosome variability in a sample from the Mediterranean islands of Corsica and Sicily, and compared with data on Sardinia to gain insights into the ethnogenesis of these island populations. The results were interpreted in a broader Mediterranean context by including in the analysis neighboring populations previously studied with the same methodology. All samples studied were enclosed in the comparable spectrum of European Y-chromosome variability. Pronounced differences were observed between the islands as well as in the percentages of haplotypes previously shown to have distinctive patterns of continental phylogeography. Approximately 60% of the Sicilian haplotypes are also prevalent in Southern Italy and Greece. Conversely, the Corsican sample had elevated levels of alternative haplotypes common in Northern Italy. Sardinia showed a haplotype ratio similar to that observed in Corsica, but with a remarkable difference in the presence of a lineage defined by marker M26, which approaches 35% in Sardinia but seems absent in Corsica. Although geographically adjacent, the data suggest different colonization histories and a minimal amount of recent gene flow between them. Our results identify possible ancestral continental sources of the various island populations and underscore the influence of founder effect and genetic drift. The Y-chromosome data are consistent with comparable mtDNA data at the RFLP haplogroup level of resolution, as well as linguistic and historic knowledge.

Chromosomes, Human, Y↗

The STR-based genetic profile of the population from Corsica island (France).

Short tandem repeats (STR) at loci HumFES/FPS, HumVWA, HumCSF1PO, HumTH01, HumFXIIIA01, HumTPOX, HumCD4, D3S1358 are markers of choice for population genetics and validated systems for forensic use. In this report, we analysed their allele frequency distribution in a sample of native blood donors from the two departments of Corsica island (France). Deviations from the Hardy-Weinberg rule and heterozygosity values consistently suggested a spatial differentiation of allele and genotype frequencies across the island. Pairwise comparisons showed that Corsican gene pool presents a high level of heterogeneity between departments and substantially differs from that of neighbouring and historically-related populations. The results suggest the use of local databases to calculate a priori statistics in human identity testing.

Alleles↗

An object oriented fully 3D tomography visual toolkit.

In this paper we present a modern object oriented component object model (COMM) C + + toolkit dedicated to fully 3D cone-beam tomography. The toolkit allows the display and visual manipulation of analytical phantoms, projection sets and volumetric data through a standard Windows graphical user interface. Data input/output is performed using proprietary file formats but import/export of industry standard file formats, including raw binary, Windows bitmap and AVI, ACR/NEMA DICOMM 3 and NCSA HDF is available. At the time of writing built-in implemented data manipulators include a basic phantom ray-tracer and a Matrox Genesis frame grabbing facility. A COMM plug-in interface is provided for user-defined custom backprojector algorithms: a simple Feldkamp ActiveX control, including source code, is provided as an example; our fast Feldkamp plug-in is also available.

Algorithms↗

Evidence of cell kinetics as predictive factor of response to radiotherapy alone or chemoradiotherapy in patients with advanced head and neck cancer.

PURPOSE: The aim of this study was to investigate the potential clinical relevance of cell kinetics parameters to the locoregional control (LRC) and overall survival of patients affected by head and neck squamous cell carcinoma (HN-SCC) treated by conventional radiotherapy, partly accelerated radiotherapy, or alternating chemoradiotherapy. METHODS AND MATERIALS: Between January 1993 and June 1996,115 patients with HN-SCC at Stage III and IV entered the study. Multiple primary tumor biopsies were obtained 6 h after in vivo infusion of bromodeoxyuridine (BrdUrd), an analogue of thymidine that is incorporated in DNA-synthesizing cells. In vivo S-phase fraction labeling index (LI), duration of S-phase (Ts), and potential doubling time (Tpot) were obtained by analysis of the flow cytometric content of BrdUrd and DNA. Eighty-two patients were randomly assigned to receive either alternating chemoradiotherapy or partly accelerated radiotherapy, whereas 33 other matching patients received conventional radiotherapy. RESULTS: Univariate LRC analysis showed that LI value was a prognostically significant factor, independent of type of therapy. Multivariate analysis failed to show cell kinetics parameters as statistically significant factors affecting LRC probability and overall survival. However, subgroup analysis showed that LRC probability at 4 years for fast proliferating tumors characterized by a LI >/= 8% was significantly better for patients treated either with alternating chemoradiotherapy or partly accelerated radiotherapy than it was for those treated with conventional radiotherapy. Conversely, LRC probability for slow proliferating tumors (LI < 8%) treated with the three treatment modalities was similar. CONCLUSIONS: These results showed that, independent of type of treatment, pretreatment cell kinetics provided only a weak prognostic role of outcome in HN-SCC. However, this report raises the hypothesis that fast growing HN-SCC may be more likely to benefit from intensified therapy, as given in this series. Cell kinetics parameters studied by the in vivo BrdUrd/flow cytometry method might be considered predictive factors of response, providing information on which type of treatment may be selected according to tumor proliferation rate.

Analysis of Variance↗

Microsatellite variation in Central Africa: an analysis of intrapopulational and interpopulational genetic diversity.

As a part of a research project on molecular variation in Central Africa, we have analyzed 10 microsatellites (CD4, CSFO, D3S1358, D18S51, D21S11, F13A1, FES, TH01, TPOX, and VWA) in the Bamileke and Ewondo from Cameroon and the Sanga and Mbenzele Pygmies from the Central African Republic (a total of 390 chromosomes). A statistically significant trend towards heterozygote deficiency was detected in the Mbenzele Pygmies. This was established through the use of powerful exact tests for the Hardy-Weinberg equilibrium. A certain degree of isolation and a small effective size may explain this finding. However, the lack of any substantial reduction in allelic diversity in the Mbenzele does not support the possibility that this group has a smaller effective size in evolutionary terms. A possible explanation based on ethnographic studies suggests that the gene flow from non-Pygmies to Pygmies could have been interrupted only in relatively recent times. The analysis of association between genotypes at pairs of independent loci indicates that the level of subheterogeneity is markedly lower in the Bamileke than in other sampled populations. This may be explained by the combined effect of larger population size, more rigid respect of clanic exogamy, and higher matrimonial mobility of the Bamileke. Finally, we have analyzed interpopulational relationships among our sampled populations and other Central African populations. The results are consistent with a previous study of protein loci (Spedini et al. 1999), which suggests the recent history of the Bamileke and Ewondo has led them to aquire a substantial genetic similarity. Furthermore, the Mbenzele Pygmies diverge from Biaka Pygmies, despite their common origin and geographical proximity. This is probably due to the differentiating effect of genetic drift, which is enhanced by the small effective size of Pygmy populations.

Africa, Central↗

Hamming clustering techniques for the identification of prognostic indices in patients with advanced head and neck cancer treated with radiation therapy.

The aim of the study is to demonstrate the usefulness of a new, non-linear classifier method, called Hamming clustering (HC), in selecting prognostic variables affecting overall survival in patients with head and neck cancer. In particular, the aim is to identify whether tumour proliferation parameters can be predictive factors of response in a set of 115 patients that receive either alternating chemo-radiotherapy or accelerated or conventional radiotherapy. HC is able to generate a set of understandable rules underlying the study objective; it can also select a subset of input variables that represent good prognostic factors. HC has been compared with other standard classifiers, providing better results in terms of classification accuracy. In particular, HC obtains the best accuracy of 74.8% (sensitivity of 51.1% and specificity of 91.2%) about survival. The rules found show that, besides the classical, well-known variables concerning the tumour dimension and the involved lymphonodes, some biological parameters, such as DNA ploidy, are also useful as predictive factors.

Aged↗

Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant.

PURPOSE: To investigate whether different procedure variables involved in the delivery of fractionated total body irradiation (TBI) impact on prognosis of patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplant (BMT). METHODS AND MATERIALS: Ninety-three consecutive patients with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT between 1 August 1983 and 30 September 1995 were conditioned with the same protocol consisting of cyclophosphamide and fractionated TBI. The planned total dose of TBI was 12 Gy (2 Gy, twice a day for 3 days). Along the 12-year period, variations in delivering TBI schedule occurred with regard to used radiation source, instantaneous dose rate, technical setting, and actual total dose received by the patient. We tested these different TBI variables as well as factors related to patient, state of disease, and transplant-induced disease to investigate their influence on transplant-related mortality, leukemia relapse, and survival. RESULTS: At median follow-up of 7 years (range 3-15 years) the probabilities of leukemia-free survival (LFS) and overall survival (OS) for the 93 patients were 60% and 41%, respectively. At univariate analysis, chronic graft versus host disease (cGvHd) (p = 0.0005), age (p = 0.01), and state of disease (p = 0.03) were factors affecting LFS whereas chronic GvHd (p = 0.0005), acute GvHd (p = 0.03), age (p = 0.0001), and GvHd prophylaxis (p = 0.01) were factors affecting overall survival. The occurrence of chronic GvHd was correlated with actually delivered TBI dose (p = 0.04). Combined stratification of prognostic factors showed that patients who received the planned total dose of TBI (12 Gy) and were affected by chronic GvHd had higher probabilities of LFS (p = 0.01) and OS (p = n.s.) than patients receiving less than 12 Gy and/or without occurrence of chronic GvHd. Moreover, TBI dose had a significant impact on LFS in patients transplanted in first remission (p = 0.05). At multivariate analysis, TBI dose was an independent factor affecting overall survival (p = 0.05) as well as chronic GvHd (p = 0.001) and age (p = 0.04). CONCLUSIONS: This retrospective analysis showed that different variables involved in TBI delivery may influence the occurrence of cGvHd and affect prognosis of patients with ALL receiving allogeneic BMT. The total dose of 12 Gy, administered in six fractions over 3 days, appears to be an effective and low toxic regimen for ALL patients transplanted in first remission.

Adolescent↗

The peopling of sub-Saharan Africa: the case study of Cameroon.

This study analyzes the distribution of ten protein genetic polymorphisms in eighteen populations from the most densely inhabited areas of Cameroon. The languages spoken belong to three different linguistic families [Afro-Asiatic (AA), Nilo-Saharan (NS) and Niger-Kordofanian (NK)]. The analysis of variation of allele frequencies indicates that the level of genetic interpopulation differentiation is rather low (F(st) = 0.011 +/- 0.006) but statistically significant (p < 0.001). This result is not unexpected because of the relatively small geographic area covered by our survey. This value is also significantly lower than the one estimated for other groups of African populations. Among the factors responsible for this, we discuss the possible role of gene flow. There is a considerable genetic differentiation among the AA populations of north Cameroon as is to be expected because they all originated from the first agriculturists of the farming "savanna complex." The Podowko and Uldeme are considerably different from all the other AA groups, probably due to the combined effect of genetic drift and isolation. In the case of the Wandala and Massa, our analyses suggest that genetic admixture with allogeneous groups (especially with the Kanuri) played an important role in determining their genetic differentiation from other AA speaking groups. The Bantu speaking populations (Bakaka, Bamileke Bassa and Ewondo, NK family, Benué Congo subfamily) settled in western and southern Cameroon are more tightly clustered than AA speaking groups. This result shows that the linguistic affinity among these four populations coincides with a substantial genetic similarity despite their different origin. Finally, the Fulbe are genetically distinct from all the populations that belong to their same linguistic phylum (NK), and closer to the neighboring Fali and Tupuri, eastern Adamawa speaking groups of north Cameroon.

Cameroon↗

Testing a biochemical model of human genetic resistance to falciparum malaria by the analysis of variation at protein and microsatellite loci.

We recently proposed a biochemical model of genetic resistance to falciparum malaria based on the role of oxidant stress (of parasitic origin) in inducing the irreversible oxidation of hemoglobin and its binding to the erythrocyte membrane (Destro-Bisol et al. 1996). To test the model, we analyzed the relationships between the polymorphisms at the hemoglobin beta chain (HBB) and red cell glutathione peroxidase (GPX1) loci in 18 populations that had been subjected to endemic malaria (Cameroon and Central African Republic). The erythrocytes of GPX1*2 heterozygotes should be more efficient in sheltering the cell membrane from irreversible oxidation and binding of hemoglobin caused by the oxidant stress exerted by Plasmodium falciparum. According to our model, the GPX1*2 allele has an epistatic effect on the HBB*A/*S genotype by lowering its protection against falciparum malaria. In turn, this should decrease the fitness of the HBB*A/*S-GPX1*2/*1 genotype. Our predictions were confirmed. In fact, we observed a clear trend toward a dissociation between the HBB*A/*S and GPX1*2/*1 genotypes in the overall data. To test alternative hypotheses, we also analyzed the genetic variation at 9 protein and 10 autosomal microsatellite loci at both the single- and the 2-locus level. We also discuss the possible relevance of an alternative biochemical pathway. The results further support the conclusions of our study because the dissociation between the GPX1*2/*1 and HBB*A/*S genotypes does not appear to be related either to a general decrease in heterozygosity or to an increased risk of sudden death in HBB*A/*S individuals.

Alleles↗

Changes over 100 years in degree of isolation of 21 parishes of the Lima Valley, Italy, assessed by surname isonymy.

Changes over 100 years (1887-1986) in degree of isolation of 21 parishes of the Lima valley, Italy, were assessed using surname analysis. Crow and Mange's inbreeding coefficients and Lasker and Kaplan's repeated pair values were calculated using 8026 marriage records; temporal changes were assessed by dividing birth cohorts into 4 time periods of 25 years each: 1887-1911, 1912-1936, 1937-1961, and 1962-1986. Analysis was carried out at 2 hierarchical levels: the population of the valley as a whole and the valley's subdivision into 21 parishes. The relationship between population size and level of isonymy during the breakdown of isolates was investigated. The results show that there is a small difference in inbreeding coefficients between the first 2 periods at either hierarchical level of analysis and a substantial decrease in marital isonymy during the study period is mostly due to the change in male random isonymy. Furthermore, the Fn value at the higher hierarchical level almost coincides with the mean F value at the lower hierarchical level, indicating that over time the parish remained the fundamental reproductive unit. Regression analysis showed that geographic isolation became increasingly important in differentiation among the parishes in population size and in levels of inbreeding. The marked deviation from equilibrium between drift and migration that characterizes the breakdown of isolates of almost all the rural populations is an important disturbing factor in assessing the relationship between level of inbreeding and population size. Comparison over time allows us to better describe the evolutionary forces at the basis of the changes in genetic structure of a population.

Cohort Studies↗

Correlations of quantitative chromosomal heteromorphisms and classic genetic markers to demogeographic data in Garfagnana valley (Tuscany, Italy).

The genetic structure and interrelationships of six populations of the Garfagnana valley (Tuscany, Italy) were examined using chromosomal heteromorphisms concurrently with blood group system, red cell isozyme, and serum protein polymorphisms, secretor status, and surname frequency data. We aimed to evaluate the relationship of cytogenetic polymorphisms to more classical sources of gene frequency data in a population with a well-known demographic scenario. The R matrix technique (Harpending and Jenkins 1973) was used to estimate kinship coefficients, and the Harpending-Ward model (1982) and its extensions for quantitative traits (Relethford and Blangero 1990) were used to detect differential systematic pressure among population subdivisions. Mantel statistics were used to assess the significance of the correlations between cytogenetic, genetic, isonymy, geographic, and migration matrices. The analyses consistently gave similar results for the DA/DAPI cytogenetic heteromorphism and most gene frequency data. Both sets of results depend on migration patterns and on geographic distance among population subdivisions. However, C cytogenetic heteromorphism and some separately analyzed genetic markers did not fit the demogeographic pattern. Overall, it appears that data from different levels of the genetic hierarchy (namely, DNA regions encoding for classical biochemical markers and the noncoding highly variable cytogenetic bands of heterochromatin) can be treated and compared using the same analytical tools.

Blood Group Antigens↗

Study of the matrimonial structure of the population of central Sardinia (Italy).

Temporal changes in the matrimonial structure of four Sardinian populations (Bitti, Lula, Lodè and Gavoi) have been studied. The endogamy rates and the average marriage distances indicate that the four villages experienced a long period of isolation. Only in recent decades endogamous marriages have fallen shortly. The trends of marital isonymy and inbreeding, evaluated both from isonymy and dispensation for consanguineous marriages, are similar to those of endogamy. The kinship values between pairs of populations show some preferential relationship (Bitti-Lodè, Lodè-Lula) and an evident differentiation between Gavoi and Bitti. The results also indicate that the values of kinship are not associated with the geographic distances. The possible impact of the matrimonial structure on the genetic structure and the relationships among the studied populations will be examined in further investigations, in which the genetic markers will be considered.

Adult↗

[An expert system for the planning of whole-body irradiation treatments].

Total body irradiation (TBI) combined with intensive chemotherapy and bone marrow transplantation is used with increasing success for the treatment of hematologic malignancies with severe prognosis. An expert system, developed on the basis of the experience acquired during the last years in our department, has been designed to optimize the different treatment steps. The choice of an expert system is based on its capabilities in reconstructing a rule-based reasoning through the combination of theoretical and empirical knowledge. Particularly, a subsystem dealing with the steps to be taken to optimize treatment in TBI has been designed using medical and physical data. Our system can determine radiation treatment variables together with a sequence of quality control procedures. Moreover, indications are given about short, medium and long term damage probabilities and toxicity estimates, both derived from literature data and our personal series of cases. Treatment quality can be assessed and the different techniques compared using these data. This project is aimed at providing physicians and physicists with useful clinical suggestions for TBI setting for bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

[Imposing "calcium milk" lithiasis in giant hydronephrosis].

The authors report a quite unusual case of "milk of calcium renal Stone" in unilateral giant Hydronephrosis. Radiographic, sonographic, intravenous urographic and TC aspects are described and prominence il given to morphostructural information obtained through digital image techniques of pyeloureteral zone junction and of "milk of calcium renal Stone". The authors discuss the pathogenesis of the renal Stone type and emphasize the convenience of investigative acts to clear up the ethio-pathogenetic role of pyeloureteral infections.

Adult↗

Isolation factors and kinship by isonymy in a group of parishes in northern Tuscany (Italy): influence of within-parish similarity level on between-parish similarity pattern.

We investigate the influence of within-parish similarity level on between-parish similarity pattern in surname analysis through a study of the relative roles of various isolation factors accounting for the population structure within a municipality (21 parishes) in the hilly part of northern Tuscany. One surname per family was collected (N = 3052), and the pattern of kinship observed by isonymy was compared with the expected patterns based on demogeographic variables. The fit of the isolation by distance model is substantially improved with the inclusion of values at zero geographic distance (i = j). Differentiation in migration rate was clearly shown by the local kinship values, which are highly correlated with the demogeographic features of the parishes under study. Furthermore, the strong heterogeneity of the local kinship values seems to be the major factor responsible for the poor relation of the off-diagonal values of the kinship matrix to the expected isolation pattern. In fact, the kinship matrix weighted on the basis of the local kinship values points to a pattern of similarity among parishes congruent with the demogeographic structure of the population. On the whole, the results indicate that at the low hierarchical level of parishes the extreme localization of surnames is a disturbing factor in population structure analysis. A simple method to overcome this problem has been proposed.

Altitude↗

Numerical method for the interpolation of digitized lines (unrolling method).

The proposed method can be used for reconstructing, from n not necessarily equidistant points of a digitized polydrome line, a set of n1 equidistant points (with n1 > n) interpolating the original points. This method is based on a transformation of the original line into a digitized monodrome function D(1i) (unrolling function), where 1i is the line length between the origin and the ith point (i = 1,..., n1). Advantage of this method consists in reducing the two-dimensional interpolation problem to the one-dimensional field. In scintigraphic imaging, it is possible to achieve interpolation and coding of ROI's (Regions Of Interest) edges. For n samples of a monodrome line this method can also be applied, representing a possible alternative to splines. The numerical procedure is developed to reduce the noise on the points.

Heart↗