Self-sampling to increase participation in cervical cancer screening: an RCT comparing home mailing, distribution in pharmacies, and recall letter.

BACKGROUND: We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter. METHODS: Women aged 30-64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat. RESULTS: In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60-1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86-1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I(2), 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder. CONCLUSIONS: Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre.

AMaCAID: a useful tool for Accurate Marker Choice for Accession Identification and Discrimination.

AMaCAID is an R program designed to analyse multilocus genotypic patterns in large samples. It allows (i) the computation of the number and frequency of the different multilocus patterns available in a molecular data set and (ii) the analysis of discriminatory power of each combination of k markers among n available. It thus enables the identification of the minimum number of markers required to distinguish all the observed genotypes and the subset of markers that maximize the number of distinct genotypes. AMaCAID can be used with any kind of molecular markers, on data sets mixing different kinds of markers, but also on qualitative characters like morphological or taxonomic traits. AMaCAID has been built primarily to select subsets of markers for identifying accessions and monitoring their genetic stability during regeneration cycles in an ex situ genebank. It can, however, also be used to screen any kind of data set that characterizes a set of individuals or species (e.g. taxonomic or phylogenetic studies) for discrimination purposes. The size of the assayed sample has no limitation, but the program only performs computations on all combinations of markers when there are less than 25 markers. For larger number of markers/characters, it is possible to ask AMaCAID to screen a large but limited number of combinations of markers. We apply AMaCAID to three data sets involving either molecular or taxonomic data and give some results on the computing time of the program with respect to the size of the data set.

Borderline tuberculoid leprosy--an unusual presentation: a case report.

A twenty-six year old lady presented herself with multiple erythmatous, scaly, well-defined, hypo-esthetic plaques over bilateral soles, face and left leg. Histopathology revealed features consistent with borderline tuberculoid leprosy.

Antitumour effect of combination treatment with Sabarubicin (MEN 10755) and cis-platin (DDP) in human lung tumour xenograft.

PURPOSE: Sabarubicin (MEN 10755), a new disaccaride anthracycline, has shown greater efficacy than Doxorubicin in a large panel of preclinical models and now it is in phase II clinical trials. Its promising antitumour activity promoted considerable interest to combine Sabarubicin with other antitumour agents. Thus, the purpose of this study was to evaluate in vitro cytotoxic effects and in vivo antitumour activities produced by the combination of Sabarubicin and cisplatin (DDP). METHODS: The antitumour effect of Sabarubicin and DDP association was investigated, in vitro and in vivo, in preclinical models of lung cancer i.e.: the non-small cell lung carcinoma (NSCLC) H460 and the small-cell lung carcinoma (SCLC) GLC4 in terms of synergism, additivity or antagonism in order to establish the best schedule for the combined treatment. Further, the correlation between antitumour activity and the pharmacokinetic parameters of the studied combination was also evaluated. RESULTS: The drug combination in vitro was in general more cytotoxic than the single drug alone, indicating the presence of a synergistic effect in both tumour cell lines. Also, in the xenograft experiments a superior antitumoral effect was observed when Sabarubicin was combined with DDP. The antitumour efficacy of Sabarubicin (6 mg/kg q4d x 5) combined with DDP (6 mg/kg q4d x 3) greatly depended on the schedule of administration. In H460 tumour line, the sequential combination was more effective than the simultaneous administration of the two agents, although the antitumour efficacy was not dependent on the sequence of combination. On the other hand, a strong sequence-dependent effect was observed when Sabarubicin was combined with DDP in SCLC, GLC4. In particular, the highest value of LCK = 6.7 was obtained when administration of DDP followed by 24 h that of Sabarubicin. Pharmacokinetics of Sabarubicin in combination with DDP was evaluated at 6 mg/kg for both drugs with different sequential schedule. The experimental data showed no evidence for pharmacokinetics drug-drug interaction. CONCLUSION: These preclinical results indicate the potential for a strong antitumour activity in lung tumours of the combination Sabarubicin and DDP. In particular, in SCLC the best response should be given by a sequence with administration of Sabarubicin followed 24 h later by that of DDP. Clinical trials based on these results are ongoing.

Homogeneity and stability study of the candidate reference material Adamussium colbecki for trace elements.

The preparation of a new candidate certified reference material (CRM) for trace elements based on the antarctic bivalve Adamussium colbecki(IRMM 813) was carried out by the Istituto Superiore di Sanità(ISS, Rome, Italy) in cooperation with the Institute for Reference Materials and Measurements, Joint Research Centre of the European Commission (EC-JRC-IRMM), in the frame of the Italian National Programme of Research in Antarctica (Programma Nazionale di Ricerca in Antartide, PNRA). Samples were collected at Terra Nova Bay (Ross Sea) during the 2000-2001 expedition in Antarctica. The preparation of a material suitable for certification was performed by the EC-JRC-IRMM. Measurements for homogeneity and short-term stability tests were carried out by ISS. The elements selected for the certification project were As, Cd, Cu, Cr, Fe, Mn, Ni and Zn. For the above-mentioned tests, the determination of the elements of interest was performed on samples mineralised by microwave-assisted acid digestion. The analytical techniques employed to this end were inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma dynamic reaction cell quadrupole mass spectrometry (ICP-DRC-Q-MS). The candidate material was shown to be fit for purpose with regard to homogeneity and short-term stability, thus allowing the following phases of the certification project to be undertaken, in the first place the selection of expert laboratories for the accomplishment of the certification campaign.

Variations in the level of some trace elements in hair of participants in the Italian expeditions in Antarctica.

As a part the Italian National Programme of Research in Antarctica (PNRA) a monitoring study has been undertaken to quantify the concentrations of some selected trace elements in human hair of participants in the Antarctic expeditions. Such concentrations may vary as a consequence of the extreme environmental conditions and changes in lifestyle experienced by participants in the expeditions, as some evidence in previous investigations seems to suggest. The present study regards samples collected on the occasion of the 2002-2003 expedition to the Italian Base of Terra Nova Bay (now Mario Zucchelli Base), i.e., just before the expedition and about one month later. Seven essential elements were taken into account, namely, Ca, Cu, Cr, Fe, Mg, Mn and Mo. Determinations were performed by Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES) and Dynamic Reaction Cell Inductively Coupled Plasma Mass Spectrometry (DRC-ICP-MS). Data obtained were statistically treated by using the non-parametric Friedman test. The concentrations of Ca, Cu and Mg were found to decrease (P < 0.05). The stress caused by the severe environmental conditions might well play a role in the observed decrease.

Biomonitoring of traffic police officers exposed to airborne platinum.

BACKGROUND: Over the past two decades there has been a substantial increase in environmental levels of palladium, platinum, and rhodium, the platinum group elements (PGEs), due to the widespread use of catalytic converters for automotive traction. AIM: To evaluate urinary platinum levels in occupationally exposed subjects. METHODS: A total of 161 employees from the Rome City Police Force were studied; 103 were traffic police involved in controlling streets with an average flow of vehicles, while the remaining 58 were control subjects engaged only in office work. Platinum quantification in the urine samples of these subjects was carried out by sector field inductively coupled plasma mass spectrometry. RESULTS: There were no statistically significant differences between platinum levels in the group of subjects engaged in traffic control and the control group (4.45 (2.42) ng/l v 4.56 (2.84) ng/l, respectively). CONCLUSIONS: Urinary levels were found to be higher than those reported for other urban populations, thus showing a progressive increase in human exposure to Pt.

Levels and risk assessment for humans and ecosystems of platinum-group elements in the airborne particles and road dust of some European cities.

Traffic is the main source of platinum-group element (PGE) contamination in populated urban areas. There is increasing concern about the hazardous effects of these new pollutants for people and for other living organisms in these areas. Airborne and road dusts, as well as tree bark and grass samples were collected at locations in the European cities of Göteborg (Sweden), Madrid (Spain), Rome (Italy), Munich (Germany), Sheffield and London (UK). Today, in spite of the large number of parameters that can influence the airborne PGE content, the results obtained so far indicate significantly higher PGE levels at traffic sites compared with the rural or non-polluted zones that have been investigated (background levels). The average Pt content in airborne particles found in downtown Madrid, Göteborg and Rome is in the range 7.3-13.1 pg m(-3). The ring roads of these cities have values in the range 4.1-17.7 pg m(-3). In Munich, a lower Pt content was found in airborne particles (4.1 pg m(-3)). The same tendency has been noted for downtown Rh, with contents in the range 2.2-2.8 pg m(-3), and in the range 0.8-3.0 and 0.3 pg m(-3) for motorway margins in Munich. The combined results obtained using a wide-range airborne classifier (WRAC) collector and a PM-10 or virtual impactor show that Pt is associated with particles for a wide range of diameters. The smaller the particle size, the lower the Pt concentration. However, in particles

Environmental risk of particulate and soluble platinum group elements released from gasoline and diesel engine catalytic converters.

A comparison of platinum-group element (PGE) emission between gasoline and diesel engine catalytic converters is reported within this work. Whole raw exhaust fumes from four catalysts of three different types were examined during their useful lifetime, from fresh to 80,000 km. Two were gasoline engine catalysts (Pt-Pd-Rh and Pd-Rh), while the other two were diesel engine catalysts (Pt). Samples were collected following the 91441 EUDC driving cycle for light-duty vehicle testing, and the sample collection device used allowed differentiation between the particulate and soluble fractions, the latter being the most relevant from an environmental point of view. Analyses were performed by inductively coupled plasma-mass spectrometry (ICP-MS) (quadrupole and high resolution), and special attention was paid to the control of spectral interference, especially in the case of Pd and Rh. The results obtained show that, for fresh catalysts, the release of particulate PGE through car exhaust fumes does not follow any particular trend, with a wide range (one-two orders of magnitude) for the content of noble metals emitted. The samples collected from 30,000-80,000 km present a more homogeneous PGE release for all catalysts studied. A decrease of approximately one order of magnitude is observed with respect to the release from fresh catalysts, except in the case of the diesel engine catalyst, for which PGE emission continued to be higher than in the case of gasoline engines. The fraction of soluble PGE was found to represent less than 10% of the total amount released from fresh catalysts. For aged catalysts, the figures are significantly higher, especially for Pd and Rh. Particulate PGE can be considered as virtually biologically inert, while soluble PGE forms can represent an environmental risk due to their bioavailability, which leads them to accumulate in the environment.

Honey as a candidate reference material for trace elements.

The feasibility of producing and certifying new certified reference materials (CRMs) for trace elements in honey was investigated. Preliminary steps for preparation of candidate materials are performed at the Institute for Reference Materials and Measurements, Joint Research Centre of the European Commission (EC-JRC-IRMM). Two different types of honey, Acacia and Eucalyptus, were tested for determination of 10 trace elements. To each type of honey was added a given amount of high purity deionized water to obtain aqueous solutions with an acceptable degree of homogeneity which would require only minimal manipulation before analysis. Average values obtained for the trace elements by means of inductively coupled plasma-based techniques were as follows (in microg/ kg +/- SD): Acacia honey, As, 1.10+/-0.20; Cd, 0.328+/-0.035; Cr, 1.90+/-0.22; Cu, 67.0+/-5; Fe, 215+/-30; Hg, < 0.75; Mn, 82.1+/-6.2; Ni, 21.0 3.0; Pb, 2.30+/-0.25; Se, 9.10+/-1.2; Zn, 167+/-22; Eucalyptus honey, As, 5.99+/-0.10; Cd, 0.592+/-0.074; Cr, 1.50+/-0.07; Cu, 219 24; Fe, 1008+/-114; Hg, <0.75; Mn, 1009+/-51; Ni, 11.3+/-1.5; Pb, 5.00+/-0.40; Se, 5.60+/-0.91; Zn, 791+/-91. When these 2 pilot materials are ready, the certification project will be launched in full compliance with current rules set by EC-JRC-IRMM. If the project is successful, the new CRMs will be put primarily at the disposal of the National Reference Laboratories for trace elements.

Platinum-group elements: quantification in collected exhaust fumes and studies of catalyst surfaces.

Automotive catalytic converters, in which Pt, Pd and Rh (platinum-group elements; PGEs) are the active components for eliminating several noxious components from exhaust fumes, have become the main source of environmental urban pollution by PGEs. This work reports on the catalyst morphology through changes in catalyst surface by scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) and laser-induced breakdown spectrometry (LIBS) from fresh to aged catalytic converters. The distribution of these elements in the fresh catalysts analysed (Pt-Pd-Rh gasoline catalyst) is not uniform and occurs mainly in a longitudinal direction. This heterogeneity seems to be greater for Pt and Pd. PGEs released by the catalysts, fresh and aged 30,000 km, were studied in parallel. Whole raw exhaust fumes from four catalysts of three different types were also examined. Two of these were gasoline catalysts (Pt-Pd Rh and Pd-Rh) and the other two were diesel catalysts (Pt). Samples were collected following the 91,441 EUDC driving cycle for light-duty vehicle testing. The results show that at 0 km the samples collected first have the highest content of particulate PGEs and although the general tendency is for the release to decrease with increasing number of samples taken, exceptions are frequent. At 30,000 km the released PGEs in gasoline and diesel catalysts decreased significantly. For fresh gasoline catalysts the mean of the total amount released was approximately 100, 250 and 50 ng km(-1) for Pt, Pd and Rh, respectively. In diesel catalysts the Pt release varied in the range 400-800 ng km-1. After ageing the catalysts up to 30,000 km, the gasoline catalysts released amounts of Pt between 6 and 8 ng km(-1), Pd between 12 and 16 ng km(-1) and Rh between 3 and 12 ng km(-1). In diesel catalysts the Pt release varied in the range 108-150 ng km(-1). The soluble portion of PGEs in the HNO3 collector solution represented less than 5% of the total amount for fresh catalysts. For 30,000 km the total amount of soluble PGEs released was similar or slightly higher than for 0 km.

Assessment of reference values for elements in human hair of urban schoolboys.

Hair samples of youngsters (3-15 years of age) from several urban areas of Rome were analyzed to determine the content of 19 minor and trace elements with the aim of assessing Reference Values (RVs). Thirteen essential elements were taken into account, Ca, Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, P, Se, V and Zn. On the other hand, Al, As, Cd, Pb, Sr and Ti were also evaluated on the basis of their potential toxicity. Procedures were developed for the collection, storage and pre-analytical treatment of samples. Measurements were performed by inductively coupled plasma atomic emission spectrometry. Subgroups were formed according to age and sex. Significant differences were found for certain elements depending on age and sex. This was the case, e.g., for Ca which showed a mean value of 336 mg/kg for males and of 537 mg/kg for females. The sex-dependent pattern for this element was also apparent when the three age subgroups of 3-6, 7-10 and 11-15 years were compared. The overall RVs obtained (mg/kg) are as follows Al, 10.2; As, 0.09; Ca, 450; Cd, 0.23; Co, 0.67; Cr, 0.99; Cu, 22.1; Fe, 19.0; Mg, 28.0; Mn, 0.35; Mo, 0.43; Ni, 1.49; P, 195; Pb, 7.11; Se, 0.77; Sr, 1.20; Ti, 0.79; V, 1.22; and Zn 150.

Reference values for selected trace elements in serum of term newborns from the urban area of Rome.

Reference values for Al, Cd, Co, Cu, Li, Mn, Mo, Ni, Rb, Se and Zn, and indicative intervals for Sb are proposed in serum from cord blood of 143 term newborns of the urban area of Rome. On the basis of the eligibility criteria adopted, only babies with gestational age > 37 weeks and body weight at the delivery > 2500 g, i.e., "normal" term infants, were included in this study. With the exception of Cd, Li, Ni and Sb, experimental data for each of the other analytes were found to approach a normal distribution. The estimated references values (in ng/ml) were the following: Al, 1. 12-6.79; Cd, 0.10-0.52; Co, 0.20-0.43; Cu, 140-691; Li, 0.31-2.23; Mn, 0.79-3.26; Mo, 0.36-1.56; Ni, 0.20-3.15; Rb, 196-1302; Sb, 0. 10-1.48 (indicative range); Se, 20.2-69.7; and Zn, 318-1405. For several elements, the information available in the relevant literature does not allow adequate comparisons to be performed. This was actually possible only for Cu, Se and Zn. The correlations between the weights at birth (BW), gestational ages (GA) and elemental concentrations were elucidated. As expected, significant positive correlations were found for Cu and Se with GA and BW, respectively. Strong mutual associations were observed for several other elements, but their interpretation is still debatable.

Reference values for chromium, nickel and vanadium in urine of youngsters from the urban area of Rome.

In the assessment of human health risk, the obtainment of reference values in biological tissues and/or fluids is crucial to estimate the type and magnitude of occupational and environmental exposure. In this context, urine is the major excretion route for many noxious substances that have entered the organism and can be viewed as one of the most useful materials for biomonitoring campaigns. In this study, reference concentration ranges for Cr, Ni and V in urine were achieved in a sub-population of 131 youngsters, aged 6-10, attending primary schools in the urban area of Rome. Subjects under drug therapy or affected by any pathological diseases were not included in this investigation. Strict precautions against contamination or loss of the analytes of interest were adopted for all steps. Determinations were performed by means of high resolution inductively coupled plasma mass spectrometry. In general, the natural log-transformed concentration data for the three elements investigated conformed to a satisfactorily normal distribution. The estimated reference ranges were as follows (microg g(-1) creatinine): Cr, 0.07-0.76; Ni, 0.20-1.23; V, 0.02-0.22. The sex of the youngsters was tentatively treated as a statistical explanatory variable using the Fischer F-test on variance.

Activity of cisplatin and ICI 182,780 on estrogen receptor negative ovarian cancer cells: cell cycle and cell replication rate perturbation, chromatin texture alteration and apoptosis induction.

The activity of cisplatin (CP, range of concentrations 0.25-1 microg/ml), the pure steroidal antiestrogen compound ICI 182,780 (range of concentrations, 0.01-10 microM) and various combinations of, was investigated on an estrogen receptor negative ovarian cancer cell line (A2780 WT) and its CP-resistant derivative subline (A2780 CP3). CP markedly reduced A2780 WT cell growth but marginally affected A2780 CP3, whereas ICI 182,780 was effective on both cell lines. CP but not ICI 182,780 provoked a significant blockade in late S/G(2) phase in both cell lines, particularly in the parental line. Measuring the number of rounds of cell replications showed that CP diminished the cell replication rate of both cell lines, particularly in A2780 WT. Conversely, ICI 182,780 reduced the cell replication rate of A2780 CP3 but not A2780 WT cells. Both drugs provoked apoptosis in A2780 WT cells, as assessed by the appearance of large (50-300 kbp) DNA fragmentation. However, laser scanning cytometry showed that only CP induced a measurable alteration of chromatin texture in A2780 WT but not in A2780 CP3 cells. The combination CP and ICI 182,780 resulted in a synergistic inhibitory activity of cell growth with a CP potentiation up to 4 and 11-fold in A2780 WT and A2780 CP3 cells, respectively. This reflected an enhanced reduction of the cell replication rate and did not involve perturbations of the cell cycle other than those provoked by CP alone. Apoptosis induction and the level of CP-DNA adducts were not influenced by adding ICI 182,780 to CP in both cell lines.

Determination of the total content and binding pattern of elements in human milk by high performance liquid chromatography-inductively coupled plasma atomic emission spectrometry.

Evidence of element speciation in biological fluids is scarce and fragmentary in the literature. On the other hand, it is well known that chemical speciation analysis is prone to error due to contamination, modification or breaking up of the metal-organic moiety link during the separation processes, as well as to insufficient detection power for element quantification in the various fractions. Therefore, there is a keen need for sensitive and reliable speciation methods. We explored the analytical capabilities of size exclusion chromatography (SEC) in conjunction with ultrasonic nebulization inductively coupled plasma atomic emission spectrometry (UN-ICP-AES) for the speciation of Ca, Cu, Fe, Mg, Mn and Zn in human milk. We applied the method to assess concentration range and binding pattern of the said elements in the milk of 60 lactating mothers (19-40 years of age) representative of different areas of Italy. The total concentration ranges found were in good agreement with those reported in the literature. These levels were as follows (in ng ml(-1)): Ca, 306 000+/-11 760; Cu, 370+/-30; Fe, 650+/-40; Mg, 23 000+/-510; Mn, 30+/-2; and Zn, 2720+/-70. The influence of factors such as age (over or under 30) and residence area (urban or rural) of the mothers on the total concentration of the elements was also evaluated. Magnesium concentration was higher for mothers >30, while higher Zn levels were found for maternal age <30. Copper was higher in women living in urban areas. Moreover, strong positive Ca-Mg and Fe-Mn associations and significant negative Cu-Zn correlations were found. The chromatographic separation yielded five fractions. The first of these presumably accounted for caseins (alpha(s), beta and k) aggregates; the second peak mainly contained immunoglobulins (Igs); the third could be traced back to human serum albumin (HSA) and lactoferrin (LF); the fourth could be entirely ascribed to alpha-lactalbumin (alpha-La); and the fifth accounted for all substances with relatively low molecular weights, such as non-proteic compounds. As anticipated, the elements investigated showed peculiar associations with the components of the milk. Copper and Fe appeared homogeneously spread over all the organic components. Calcium and Mg preferably bound to low molecular weight compounds. Manganese had a peculiar pattern as it was found in considerable percentage in the first and fifth fractions. As for Zn, the highest percentage was found in the fraction corresponding to alpha-lactalbumin.

Minor and trace element content of two typical Italian sheep dairy products.

The concentration ranges in milk and cheese of a number of metallic elements relevant to the health of the consumer are dependent upon animal species, feeding, time of year, environmental conditions and manufacturing processes. We have measured the concentrations of selected trace elements--Al, Ba, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Pt, Sr and Zn--in raw ewes' milk and typical ewes' milk cheeses. Samples of milk, curd, whey, cheese after moulding, cheese after salting, commercial cheese (Pecorino), Ricotta, scotta and brine were analyzed for seven complete cycles of cheese production. Samples of curd, whey, brine and waste product (i.e. scotta) were collected and analysed in addition to the cheese and milk to assess the distribution of each element in the main product, by-products and waste products during cheesemaking. Quantitative determinations were performed mainly by inductively coupled plasma atomic emission spectrometry. There were considerable differences among the trace element contents of raw ewes' milk and related products, indicating that manufacturing processes play a key role in the distribution of minor and trace elements. Two different approaches were used to assess the dietary intake of these elements associated with the consumption of Pecorino and Ricotta, and whether this had any nutritional or toxicological implications. The results indicated no toxicological risk and showed that, on the contrary, Pecorino may be a good source of several essential elements.