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Biomedical subjects

C Andreoli

Publications and source records attributed to C Andreoli.

At least 19 recordsLinked to original sources

Early detection of cancer: ideas for a debate.

Even if the overall number of cancer is increasing, the mortality has started to decrease in the Western World. The role of early detection in this decrease is a matter of debate. To assess its impact on mortality it is important to distinguish between diagnosis of cancer in symptomatic patients, and early detection in asymptomatic individuals who may self-refer or who may be offered ad hoc or systematic screening. The policies for early detection and screening vary greatly between European countries, despite many similarities in their cancer burden, and this partly reflects the uncertainties surrounding asymptomatic testing for cancer. A Task Force of European expert, held in Azzate (VA), Italy, established to address these issues, acknowledged the need for more research in the field of individual risk assessment since general statistics are more and more perceived as inadequate to design personal early detection plans. The group also recognised that combinations of early detection and screening will enforce the effectiveness of new treatments in curbing mortality curves, although policies will vary with different cancers.

Breast Neoplasms↗

Influence of DNA repair polymorphisms on biomarkers of genotoxic damage in peripheral lymphocytes of healthy subjects.

DNA repair polymorphisms may represent susceptibility factors affecting DNA integrity, and possibly cancer risk, in human population. In order to elucidate the influence of a few widely studied DNA repair polymorphisms on individual levels of DNA damage and their possible interaction with lifestyle and environmental exposures, 171 subjects from a well-characterized human population enrolled in a previous study on genetic effects of air pollution were genotyped for the XRCC1 Arg280His and Arg399Glu, XRCC3 Thr241Met and ERCC2 Lys751Gln polymorphisms. The association between DNA repair genotype, alone or in combination with metabolic genotype, on the levels of SCE, micronuclei and tail moment values in peripheral lymphocytes was evaluated. A significant influence of the ERCC2 genotype on SCE frequency was observed. Subjects with ERCC2 751 Gln/Gln genotype had significantly higher risk of high (above the median) SCE/cell with respect to Lys/Lys referents (OR 4.55, 95% CI 1.48-13.99). A non-significantly elevated OR was also observed in Gln/Lys heterozygotes, suggesting a gene dosage effect. When subjects were categorized by smoking habits and professional exposure, the variant ERCC2 751 Gln/Gln genotype was associated with elevated SCE rates in non-smokers and in exposed subjects, but not in smokers. The results of this study support the hypothesis that some DNA repair polymorphisms exert a modifying effect on individual levels of DNA damage in healthy subjects, possibly also modulating cancer risk.

Adult↗

MitoP2: the mitochondrial proteome database--now including mouse data.

The MitoP2 database (http://www.mitop.de) integrates information on mitochondrial proteins, their molecular functions and associated diseases. The central database features are manually annotated reference proteins localized or functionally associated with mitochondria supplied for yeast, human and mouse. MitoP2 enables (i) the identification of putative orthologous proteins between these species to study evolutionarily conserved functions and pathways; (ii) the integration of data from systematic genome-wide studies such as proteomics and deletion phenotype screening; (iii) the prediction of novel mitochondrial proteins using data integration and the assignment of evidence scores; and (iv) systematic searches that aim to find the genes that underlie common and rare mitochondrial diseases. The data and analysis files are referenced to data sources in PubMed and other online databases and can be easily downloaded. MitoP2 users can explore the relationship between mitochondrial dysfunctions and disease and utilize this information to conduct systems biology approaches on mitochondria.

Animals↗

MitoP2, an integrated database on mitochondrial proteins in yeast and man.

The aim of the MitoP2 database (http://ihg.gsf.de/mitop2) is to provide a comprehensive list of mitochondrial proteins of yeast and man. Based on the current literature we created an annotated reference set of yeast and human proteins. In addition, data sets relevant to the study of the mitochondrial proteome are integrated and accessible via search tools and links. They include computational predictions of signalling sequences, and summarize results from proteome mapping, mutant screening, expression profiling, protein-protein interaction and cellular sublocalization studies. For each individual approach, specificity and sensitivity for allocating mitochondrial proteins was calculated. By providing the evidence for mitochondrial candidate proteins the MitoP2 database lends itself to the genetic characterization of human mitochondriopathies.

Computational Biology↗

Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects.

Gene-environment interactions play an important role in folate metabolism, with a potential impact on human health. Deficiencies in the uptake of key micronutrients and variant genotypes can affect the folic acid cycle, modulating methyl group transfer in key processes and leading to increased cancer risk and Down syndrome incidence. So far, the significance of folate status and metabolic genotypes on baseline levels of DNA damage in normal individuals has not been fully elucidated. In this study, the possible modulation of SCE, micronuclei and tail moment values in peripheral lymphocytes by plasma levels of folic acid, homocysteine and vitamin B12, and by the methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms was investigated in 191 healthy subjects. The results obtained show a highly significant (P = 0.001) positive association between plasma levels of vitamin B12 and frequencies of both SCE and high frequency cells (HFC, above 90 degrees percentile) in smokers. No significant effect was observed in non-smokers. Moreover, after correction for age, gender and GSTM1 genotype, a significant association (P = 0.026) between the MTRR 66GG variant genotype and higher micronucleus rates was observed. Tail moment values were not affected by any of the independent variables considered. Overall, the results obtained suggest that both folate status and relevant metabolic genotype can influence background levels of DNA damage in normal subjects. The significant association observed in smokers between plasma vitamin B12 and SCE frequencies may highlight the effect of methylation status on DNA damage and repair, although the role of other, unidentified dietary factors cannot be ruled out. At the same time, micronucleus data indicate that the MTRR 66GG variant may represent another individual trait of relative genomic instability, thus supporting epidemiological data on increased risk of Down syndrome conception in MTRR 66GG subjects.

Adult↗

Hematocolpos in double vagina associated with uterus didelphus: US and MR findings.

The malformative syndrome of double vagina in association with uterus didelphus and kidney agenesis is a rare condition, often asymptomatic: if this condition is accompanied by imperforated obstructed hemivagina, the clinical manifestations depend on the presence of hematocolpos. MRI plays an important role for diagnosis because it allows to characterize the nature of the lesion and to evaluate the anatomical details of the uterine malformation. The authors describe this complex genital malformation and discuss the main US and MRI features.

Adolescent↗

Biomonitoring of exposure to urban air pollutants: analysis of sister chromatid exchanges and DNA lesions in peripheral lymphocytes of traffic policemen.

In order to elucidate the health effects of occupational exposure to traffic fumes, a few biomarkers of early genetic effect were investigated in Rome traffic policemen. One hundred and ninety healthy subjects engaged in traffic control (133 subjects) or in office work (57 subjects) participated the study. For all subjects, detailed information on smoking habits and other potential confounders were recorded by questionnaires. Average exposure of the study groups to benzene and other aromatic hydrocarbons was evaluated in a parallel exposure survey. All workers were genotyped for the following metabolic polymorphisms: CYP1A1 (m1, m2, and m4 variants), CYP2E1 (PstI and RsaI), NQO1 (Hinf1), GSTM1 and GSTT1 (null variants). In this paper, the results of the analysis of sister chromatid exchanges (SCE) in peripheral lymphocytes, and DNA damage by alkaline (pH 13) comet assay in mononuclear blood cells are reported. No statistically significant difference in the frequency of SCE or high frequency cells (HFC) was observed between traffic wardens and office workers (controls), despite the significantly higher exposure to benzene of the former (average group exposure 9.5 versus 3.8microg/m(3), 7h TWA). Conversely, both SCE per cell and HFC were highly significantly (P<0.001) increased in smokers compared to nonsmokers, showing a significant correlation (P<0.001) with the number of cigarettes per day. Multiple regression analyses of data, with metabolic polymorphisms, smoking habits, alcohol consumption, age, gender, and family history of cancer as independent variables, showed that smoking habits, and possibly the CYP2E1 variant genotypes, were the main factors explaining the variance of both SCE and HFC. Within smokers, an association of borderline significance between the CYP1A1 variant genotypes and increased SCE (P=0.050) and HFC (P=0.090) was found. This effect was mainly observed in light smokers (<15 cigarettes per day). The analysis of DNA damage by comet assay did not highlight any statistically significant difference between the exposed and control workers. Moreover, no significant model explaining tail moment variance was obtained by multiple regression analysis using the independent variables shown above. On the whole, these results indicate that exposure to moderate air pollution levels does not result in a detectable increase of genetic damage in blood cells. This evidence does not rule out any possibility of adverse effects, but strongly suggests that in urban residents life-style related factors, such as tobacco smoking, give the prevailing contribution to individual genotoxic burden.

Adult↗

[Isolated blunt hepatic traumas: role of emergency CT in therapeutic choice].

INTRODUCTION: The purpose of the study was to establish the role of score-based CT classification of hepatic lesions, peritoneal and retroperitoneal bleeding in the blunt hepatic trauma. MATERIAL AND METHODS: CT examinations of 47 haemodynamically stable patients, with isolated traumatic hepatic lesions were reviewed. CT scans were obtained with a spiral CT (thickness mm 10, pitch of 1) before and after 60 seconds after from intravenous administration of 140 cc of contrast medium at a rate of 2 cc/sec). Eleven out of 47 patients underwent surgery immediately after the CT examination, 2/47 patients in 48 hours; 34/47 patients were treated conservatively with CT follow-up on days 3 and 7, and before dimission discharge. The hepatic lesions, and degree of peritoneal and retroperitoneal haemorrhage were classified using the following scale: 1-5 for the hepatic lesions, in according to the Mirvis classification; 0-3 for peritoneal haemorrhage (0=no haemorrhage, 1=minor mild haemorrhage, 2=moderate haemorrhage, 3=major massive haemorrhage); 0-2 for retroperitoneal haemorrhage (0=no haemorrhage, 1=haemorrhage confined to the anterior pararenal space, 2=haemorrhage in 2 or more retroperitoneal spaces). The score was correlated to the treatment decisions (follow-up or surgery). RESULTS: Based on the hepatic lesion scores, we classified: 4 patients as grade 1 of grade 1, 9 as grade 2, 22 as grade 3, 11 as grade 4, 1 as grade 5; based on peritoneal haemorrhage, 14 patients as grade 0, 9 as grade 1, 8 as grade 2, and 10 as grade 3; based on retroperitoneal haemorrhage, 36 patients as grade 0 of grade 0, 3 as grade 1, and 8 as grade 2. The overall scores of the 13 patients that who underwent surgery were: 6 in 6 patients, 7 in 4 patients, 8, 9, and 10 in 1 patient. DISCUSSION AND CONCLUSIONS: CT is the modality of reference for evaluating traumatic hepatic lesions. The selection of patients for surgery requires an accurate classification and grading of the lesions. The classification of hepatic lesions alone, however, is not sufficient, as it does not take into account peritoneal and retroperitoneal haemorrhage, that which often occurs, and are correlated with the need for exploratory laparotomy. Integrated score-based evaluation of the hepatic lesions, peritoneal and retroperitoneal haemorrhage shows a good correlation with treatment decisions and clinical outcome.

Contrast Media↗

Hemoretroperitoneum associated with liver bare area injuries: CT evaluation.

In hepatic injury restricted to the postero-superior region of segment VII (bare area), hemoperitoneum may be absent and this condition may be associated with hemoretroperitoneum. The aim of this paper is to present the association between bare area injuries and hemoretroperitoneum evaluated by CT. The CT examinations of 32 patients with blunt liver trauma were reviewed and the number and location of lesions were evaluated. Right lobe involvement was identified, focusing on the bare area lesions. The presence of hemoperitoneum and hemoretroperitoneum were determined. In the 32 patients 44 parenchymal lesions were detected. Segment VII was involved in 16 cases: 5 patients presented an intraparenchymal lesion, 11 patients a lesion emerging to the liver surface. In 8 cases the lesion was localized in the bare area. In the 16 patients presenting a segment-VII lesion, hemoperitoneum was detected in 3 cases, hemoretroperitoneum in 4 cases, and both conditions in 4 cases. A traumatic hepatic lesion may be associated with hemoretroperitoneum rather than hemoperitoneum. This justifies the absence of clinical signals of peritoneal irritation; the negativity of both US scan and peritoneal lavage may cause an inappropriate therapeutic management. Computed tomography yields both the detection of the parenchymal damage and the correct localization of the intraperitoneal and retroperitoneal hemorrhage.

Hemoperitoneum↗

[US and CT findings in complicated Meckel diverticulum].

AIM: Meckel s diverticulum is the most common congenital abnormality of the small bowel. It may be silent or symptomatic when complicated by hemorrage, intestinal occlusion, diverticulitis and umbilical fistulas. Radiologic diagnosis is often difficult because abdominal plain radiography and ultrasound are not sufficiently specific; CT is most accurate in differential diagnosis. MATERIAL AND METHODS. 11 patients (age 5-69 ys) were studied. Clinical symptoms included acute abdomen (4 pts), intestinal occlusion (3 pts), abdominal pain (4 pts), fever (5 pts). Radiological studies were abdominal plain radiography (8 pts), ultrasound (5 pts), CT (9 pts). RESULTS: Abdominal plain radiography depicted signs of intestinal occlusion (4 pts) and perforation (1 pts); in 4 pts the signs were non diagnostic. Ultrasound showed an abscess in the pelvis (2 pts), dilatation and wall-thickening of an intestinal loop (2 pts), intestinal invagination (1 pts); it was not diagnostic in 3 pts. CT was not diagnostic in 3 pts; in 2 pts it showed an abscessual fluid collection in the pelvis, adherent to intestinal loops, with flogosis of the perivisceral fat; in 1 pt it revealed perforation; in 4 cases it was specific showing inversion of the diverticulum in an intestinal loop (2 pts) or a tubular fluid-filled structure, with thickened walls and contrast enhancement, which was interpreted as a inflammatory diverticulum (2 pts). DISCUSSION: Our series confirms the difficulty of diagnosing Meckel s diverticulum in an acute setting. Abdominal plain radiography only allowed to diagnose intestinal occlusion or perforation. Ultrasound revealed abscessual collections in the pelvis, fluid distention of the diverticulum, segmental thickening of the intestinal walls and invagination. CT proved to be more specific showing signs suggestive of correct diagnosis in 6 pts. In particular, evidence of an intraluminal prolonged mass with central area of fat density and peripherral collar was considered suggestive of intraluminal invagination of Meckel s diverticulum. Another diagnostic sign is the evidence of a tubular fluid-filled structure, with thickened, enhanced walls. In 2 cases CT showed an abscessual collection with gas-fluid level (complication of perforation) confirming the need for surgery. CONCLUSION: Meckel s diverticulum is a not uncommon condition that in some cases is complicated, resulting in acute abdomen. Preoperative radiological diagnosis can be suspected in the presence of suggestive signs, more often depicted by CT.

Adolescent↗

[Spontaneous pneumomediastinum: radiologic and CT study].

Pneumomediastinum may be due to various diseases. In young adults without thoracic trauma or pulmonary or mediastinal diseases pneumomediastium is secondary to mild strain or cough. This disease is defined as spontaneous pneumomediastinum or Hamman's syndrome, with a good prognosis, and doesn't need any treatment. X-ray and CT of the chest can provide correct diagnosis and adequate treatment.

Adolescent↗

DNA damage by hydroquinone in human white blood cells: analysis by alkaline single-cell gel electrophoresis.

The genotoxicity of hydroquinone (HQ) in human white blood cells was investigated by means of alkaline single-cell gel electrophoresis (SCGE). The exposure of purified lymphocytes to HQ (0.5-50 microg/ml) produced significant and dose-related increases in DNA migration; conversely, no induction of DNA damage was observed in leukocytes after in vitro treatment of whole blood samples (100-500 microg/ml). Similar differences in DNA damage between whole blood samples and purified lymphocytes were observed after treatments with hydrogen peroxide (H2O2, 50 microM). The DNA damaging activity of HQ was significantly (p<0.001, U-test) inhibited by exogenous catalase (250 U/ml), indicating the generation of peroxides in the mechanism of genotoxicity of HQ. Parallel experiments using the standard SCGE protocol, and an acellular method entailing the lysis of cells before HQ treatment, provided fairly similar results, indicating that HQ oxidation does not require endogenous metabolism. Experiments to compare the effectiveness of HQ in the induction of single-strand breaks and alkali-labile sites in resting cells and micronuclei in cytokinesis-blocked cells indicate that despite the extensive DNA damage detected by SCGE immediately after treatment, a significant excess of micronuclei is not observed after stimulation and in vitro cultivation. These data explain the apparent discrepancy between the high DNA damaging potential of HQ in human lymphocytes, as revealed by SCGE, and the relatively low activity reported in most cytogenetic assays with HQ on the same cell type.

Adult↗

Processing of DNA damage induced by hydrogen peroxide and methyl methanesulfonate in human lymphocytes: analysis by alkaline single cell gel electrophoresis and cytogenetic methods.

The persistence of induced DNA damage in human lymphocytes after mitogen stimulation and its relationship to subsequent cytogenetic alterations were investigated. The analysis of single-strand breaks and alkali-labile sites by single cell gel electrophoresis (SCGE) showed the almost complete repair of damage induced in resting lymphocytes by methyl methanesulfonate (MMS, 140-210 microM) and hydrogen peroxide (H(2)O(2), 25-100 microM) during the first 16 h of culture. On the other hand, DNA damage was shown to persist to a large extent when cells were cultured in the presence of the repair inhibitor cytosine beta-D-arabinofuranoside (Ara-C) (1 microg/ml). Although highly effective in the induction of DNA lesions detectable by SCGE, both agents failed to significantly increase the rate of micronucleus formation in cytokinesis-blocked cells harvested 66 h after treatment. However, when Ara-C was present during the first 16 h of culture, micronuclei were significantly increased at all doses. Conversely, sister chromatid exchange (SCE) rates were increased by chemical treatments to a higher extent in cultures without Ara-C. Delayed treatments, 16 h after mitogen stimulation, led to a significant induction of micronuclei in the case of MMS but not with H2O(2). These results suggest that only a minor fraction of DNA damage induced in resting lymphocytes is available for fixation through misreplication, because of its effective repair prior to S phase. However, the processing of damage through recombination pathways can lead to increased SCE rates in treated cells. These features of the processing of DNA damage in human lymphocytes should be taken into account when structural cytogenetic alterations in cultured lymphocytes are used in monitoring human exposure to genotoxic agents.

Adult↗

Color Doppler sonography of focal lesions of the skin and subcutaneous tissue.

We evaluated with color Doppler sonography 71 visible and palpable nodules of the skin and subcutaneous tissue from 51 patients. The nodules were classified as avascular (type I), hypovascular with a single vascular pole (type II), hypervascular with multiple peripheral poles (type III), and hypervascular with internal vessels (type IV). Of the 32 malignant nodules, 9% showed a type I pattern, 50% had a type III pattern, and 41% had a type IV pattern; of the 39 benign nodules, 86% showed a type I pattern and 14% had a type II pattern. The sensitivity and specificity of hypervascularity in malignant lesions were 90% and 100%, respectively, whereas the sensitivity and specificity of hypovascularity in benign lesions were 100% and 90%, respectively. The authors conclude that color Doppler sonography is able to increase the specificity of ultrasonography in the evaluation of nodular lesions of the skin.

Biopsy, Needle↗

[Proficiency test in clinical mammography. Results of a consecutive series of 130 volunteer Italian radiologists].

PURPOSE: We evaluated the results obtained by 130 Italian radiologists undergoing a proficiency test of clinical mammography. MATERIAL AND METHODS: Radiologists were invited to report a series of 100 mammograms (two views), including 32 cancers and 78 non-cancers, with limited information regarding age, subjective symptoms, and findings at palpation. Sensitivity and specificity were then calculated. The test was validated by a panel of experts, and standards for test sufficiency were established on that basis (sensitivity > 80%, specificity > 85%). The tested radiologists differed by mammographic practice (average = 5.7 years, range 0.5-18), total number of mammograms read (average = 8,784, range 300-50,000) and per year (average = 1,535 range 300-5,000). RESULTS: Sensitivity (standard > 80%, average 81.1%, range 39-100%) and specificity (standard > 85%, average 84.0%, range 38-98%) standards were reached by 79 (60.8%) and 81 (62.3%) radiologists, respectively. Overall, only 37 (28.5%) radiologists passed the test (reached both standards). Mammographic practice (years of experience) (chi 2 for trend 5.26, p = 0.02), total mammograms read (chi 2 5.86, p = 0.05), and mammograms read per year (chi 2 8.07, p = 0.01) significantly correlated with a sufficient test. DISCUSSION: The evaluated sample is rather large but not necessarily representative of Italian radiologists. Had the sample been selected, there is no way to know if the results would have been biased towards a better or worse figure with respect to the national average. A significant correlation was found with reading experience (the best results were obtained by operators with > 10,000 films read and with > 2,000 films read/year), as which is important because most Italian radiologists reporting mammography usually read a limited number of cases. CONCLUSIONS: These results on such a wide sample of radiologists, possibly representative of the national average, are disappointing, and suggest that the average quality of mammography reporting in Italy may not be up to standards. Thus, we suggest that quality control program for clinical mammography not only test the equipment but include training and accreditation of radiologists.

Clinical Competence↗

Analysis of micronuclei and DNA single-strand breaks in mouse splenocytes and peripheral lymphocytes after oral administration of tetramethylthiuram disulfide (thiram).

The fungicide thiram (tetramethylthiuram disulfide, TMTD) was administered by repeated oral intubations to groups of male B6C3F1 mice at 100, 300 and 900 mg/kg body weight for 4 consecutive days, or at 300 mg/kg for 8 and 12 days. 24 hr after the last treatment animals were killed, and splenocyte cultures were set up for the analysis of micronuclei by the cytokinesis-block method. DNA single strand breaks (ssb) and alkali labile sites were also analysed by the single cell gel electrophoresis (Comet) assay in splenocytes and lymphocytes of animals receiving the 8- and 12-day treatments. Parallel experiments with human peripheral lymphocytes were carried out to assess the ability of thiram to induce micronuclei and DNA ssb and alkaline labile sites under in vitro conditions. No significant increase of micronucleated splenocytes was observed in treated animals, despite some evidence of treatment-related cellular toxicity. A borderline excess of DNA damage was suggested by the Comet assay on circulating lymphocytes, whereas negative results were obtained with splenocytes. In vitro, positive results with both genetic end points were obtained in assays with human lymphocytes in the dose ranges 0.5-24 microg/ml and 0.1-8 microg/ml for micronucleus and Comet assays, respectively. These results suggest that thiram, despite its established genotoxicity in vitro, is devoid of appreciable clastogenic and/or aneugenic activity in vivo after oral administration to mice at the maximum tolerated dose.

Administration, Oral↗

Detection of DNA damage in human lymphocytes by alkaline single cell gel electrophoresis after exposure to benzene or benzene metabolites.

The alkaline single cell gel electrophoresis (Comet) assay was applied to study the occurrence of DNA damage in peripheral lymphocytes of human subjects with occupational exposure to low levels of benzene (twelve gasoline station attendants, with average benzene exposure of 0.3 mg/m3, 8 h TWA). The results obtained show a significant excess of DNA damage in lymphocytes of exposed workers, compared to matched unexposed controls (p = 0.028, Mann-Whitney U-test). Averaged tail moment values, based on 100 cells/individual, were 1.900 microns in the exposed and 0.936 micron in the unexposed group. In addition, exposed subjects showed a clearcut excess of heavily damaged cells, with tail moments > 90th percentile of the overall distribution (13.5 vs. 6.5%, p = 0.013, Mann-Whitney U-test). No correlation was found between the extent of DNA damage and the ages or smoking habits of the subjects. In order to assess the plausibility of the involvement of benzene in the results of the ex vivo study, further experiments were performed treating in vitro peripheral lymphocytes from unexposed donors with benzene metabolites hydroquinone, benzoquinone and benzenetriol. In these experiments, all benzene metabolites exerted a marked effect on resting lymphocytes, the lowest effective concentrations being below 1 microgram/ml. Conversely, far greater concentrations were required for the induction of significant DNA damage in parallel experiments with hydroquinone on mitogen stimulated lymphocytes. Addition of the DNA repair inhibitor cytosine arabinoside (Ara-C, 1-10 micrograms/ml) partially restored the sensitivity of stimulated cells to hydroquinone, an indication of the active processing of induced DNA lesions in growing cells. These results are discussed also in relation to the role of peripheral lymphocytes as target tissue in the biomonitoring of human exposure to genotoxic agents.

Age Factors↗