Robustness analysis of surface-guided DIBH left breast radiotherapy: personalized dosimetric effect of real intrafractional motion within the beam gating thresholds.

PURPOSE: The robustness of surface-guided (SG) deep-inspiration breath-hold (DIBH) radiotherapy (RT) for left breast cancer was evaluated by investigating any potential dosimetric effects due to the residual intrafractional motion allowed by the selected beam gating thresholds. The potential reduction of DIBH benefits in terms of organs at risk (OARs) sparing and target coverage was evaluated for conformational (3DCRT) and intensity-modulated radiation therapy (IMRT) techniques. METHODS: A total of 192 fractions of SGRT DIBH left breast 3DCRT treatment for 12 patients were analyzed. For each fraction, the average of the real-time displacement between the isocenter on the daily reference surface and on the live surface ("SGRT shift") during beam-on was evaluated and applied to the original plan isocenter. The dose distribution for the treatment beams with the new isocenter point was then calculated and the total plan dose distribution was obtained by summing the estimated perturbed dose for each fraction. Then, for each patient, the original plan and the perturbed one were compared by means of Wilcoxon test for target coverage and OAR dose-volume histogram (DVH) metrics. A global plan quality score was calculated to assess the overall plan robustness against intrafractional motion of both 3DCRT and IMRT techniques. RESULTS: Target coverage and OAR DVH metrics did not show significant variations between the original and the perturbed plan for the IMRT techniques. 3DCRT plans showed significant variations for the left descending coronary artery (LAD) and the humerus only. However, none of the dose metrics exceeded the mandatory dose constraints for any of the analyzed plans. The global plan quality analysis indicated that both 3DCRT and IMRT techniques were affected by the isocenter shifts in the same way and, generally, the residual isocenter shifts more likely tend to worsen the plan in all cases. CONCLUSION: The DIBH technique proved to be robust against residual intrafractional isocenter shifts allowed by the selected SGRT beam-hold thresholds. Small-volume OARs located near high dose gradients showed significant marginal deteriorations in the perturbed plans with the 3DCRT technique only. Global plan quality was mainly influenced by patient anatomy and treatment beam geometry rather than the technique adopted.

Hyaluronan-estradiol nanogels as potential drug carriers to target ER+ breast cancer cell line.

An innovative hyaluronan-based nano-delivery system is proposed for the active targeting towards ER+ breast cancer. Hyaluronic acid (HA), an endogenous and bioactive anionic polysaccharide, is functionalized with estradiol (ES), a sexual hormone involved in the development of some hormone-dependent tumors, to give an amphiphilic derivative (HA-ES) able to spontaneously self-assemble in water to form soft nanoparticles or nanogels (NHs). The synthetic strategy used to obtain the polymer derivatives and the physico-chemical properties of the obtained nanogels (ES-NHs) are reported. ES-NHs ability to entrap hydrophobic molecules has also been investigated, by loading curcumin (CUR) and docetaxel (DTX), both able to inhibit the growth of ER+ breast cancer. The formulations are studied for their capability to inhibit the growth of the MCF-7 cell line, thus evaluating their efficacy and potential as a selective drug delivery systems. Our results demonstrate that ES-NHs have not toxic effects on the cell line, and that both ES-NHs/CUR and ES-NHs/DTX treatments inhibit MCF-7 cell growth, with ES-NHs/DTX effect higher than that of free DTX. Our findings support the use of ES-NHs to deliver drugs to ER+ breast cancer cells, assuming a receptor-dependent targeting.

Surface-guided DIBH radiotherapy for left breast cancer: impact of different thresholds on intrafractional motion monitoring and DIBH stability.

PURPOSE: To compare two left breast cancer patient cohorts (tangential vs. locoregional deep-inspiration breath-hold - DIBH treatment) with different predefined beam gating thresholds and to evaluate their impact on motion management and DIBH stability. METHODS: An SGRT-based clinical workflow was adopted for the DIBH treatment. Intrafractional monitoring was performed by tracking both the respiratory signal and the real-time displacement between the isocenter on the daily reference surface and on the live surface ("SGRT shift"). Beam gating tolerances were 5 mm/4 mm for the SGRT shifts and 5 mm/3 mm for the gating window amplitude for breast tangential and breast + lymph nodes locoregional treatments, respectively. A total of 24 patients, 12 treated with a tangential technique and 12 with a locoregional technique, were evaluated for a total number of 684 fractions. Statistical distributions of SGRT shift and respiratory signal for each treatment fraction, for each patient treatment, and for the two population samples were generated. RESULTS: Lateral cumulative distributions of SGRT shifts for both locoregional and tangential samples were consistent with a null shift, whereas longitudinal and vertical ones were slightly negative (mean values < 1 mm). The distribution of the percentage of beam on time with SGRT shift > 3 mm, > 4 mm, or > 5 mm was extended toward higher values for the tangential sample than for the locoregional sample. The variability in the DIBH respiration signal was significantly greater for the tangential sample. CONCLUSION: Different beam gating thresholds for surface-guided DIBH treatment of left breast cancer can impact motion management and DIBH stability by reducing the frequency of the maximum SGRT shift and increasing respiration signal stability when tighter thresholds are adopted.

Underprescription of medications in older adults: causes, consequences and solutions-a narrative review.

PURPOSE: Under-prescription is defined as the omission of a medication that is indicated for the treatment of a condition or a disease, without any valid reason for not prescribing it. The aim of this review is to provide an updated overview of under-prescription, summarizing the available evidence concerning its prevalence, causes, consequences and potential interventions to reduce it. METHODS: A PubMed search was performed, using the following keywords: under-prescription; under-treatment; prescribing omission; older adults; polypharmacy; cardiovascular drugs; osteoporosis; anticoagulant. The list of articles was evaluated by two authors who selected the most relevant of them. The reference lists of retrieved articles were screened for additional pertinent studies. RESULTS: Although several pharmacological therapies are safe and effective in older patients, under-prescription remains widespread in the older population, with a prevalence ranging from 22 to 70%. Several drugs are underused, including cardiovascular, oral anticoagulant and anti-osteoporotic drugs. Many factors are associated with under-prescription, e.g. multi-morbidity, polypharmacy, dementia, frailty, risk of adverse drug events, absence of specific clinical trials in older patients and economic factors. Under-prescription is associated with negative consequences, such as higher risk of cardiovascular events, worsening disability, hospitalization and death. The implementation of explicit criteria for under-prescription, the use of the comprehensive geriatric assessment by geriatricians, and the involvement of a clinical pharmacist seem to be promising options to reduce under-prescription. CONCLUSION: Under-prescription remains widespread in the older population. Further studies should be performed, to provide a better comprehension of this phenomenon and to confirm the efficacy of corrective interventions.

[Size distribution of amphibole fibres from lung and pleural tissues sampled from mesothelioma cases due to environmental exposure]. / Caratterizzazione dimensionale di fibre anfiboliche nel polmone e nella pleura di casi di mesotelioma da esposizione ambientale.

BACKGROUND: It has been suggested that malignant mesothelioma might be mainly or only connected with the action of short and ultrathin fibres. On the basis of this hypothesis fibres less than 5 microm long and 0.2-0.1 microm thick would enter the pulmonary-pleura barrier and reach the parietal pleura thus inducing mesothelioma. The hypothesis raised a stimulating scientific discussion. OBJECTIVES: The aim of this communication is to report the initial results obtained comparing the size of amphibole fibres from healthy lung tissue with those from pleural tissue sampled from subjects whose death cause of death was mesothelioma. METHODS: Four mesothelioma cases due to environmental exposure were studied; the fibres were categorized by scanning electron microscopy; for every fibre, length and diameter were measured and the mineral type was defined by its chemical composition determined by X-ray microanalysis. RESULTS: The most important characteristics of the detected fibres were: the average length offibres from the lung and pleural tissues taken from the same subject did not difer, in all cases, by more than 10-12%; 95% offibres found in the lung tissues of all subjects had a length greater than 5 microm; 98% of fibres found in the pleural tissues had a length greater than 5 microm; the average diameter of the fibres found in the pleural tissues was 70% of the diameter of the fibres from the lung tissues. CONCLUSIONS: The experimental data obtained in this study confirm the correlation between malignant mesothelioma and the presence in the lung and pleural tissues of fibres with a length greater, even much greater, than 4-5 microm; thus the hypothesis that the chief factors inducing mesothelioma are the "ultrashort" and "ultrathin" fibres appears rather weak.

Use of tamoxifen in pT1a-pT1b, pN0 breast cancer.

PURPOSE: To evaluate if in low-risk breast cancer patients (pT1a-pT1b, pN0) tamoxifen can reduce local recurrence and improve survival. METHODS: Retrospectively 700 patients were analyzed. All patients were treated from 1980 to 2003 with conservative surgery plus radiotherapy at the University of Florence. No patients were treated with adjuvant chemotherapy. Tamoxifen was prescribed in 359 patients (51.3%). The crude probability of survival (or local recurrence) was estimated by using Kaplan-Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. RESULTS: The univariate analysis for specific survival showed that only histological type and local recurrence were significant prognostic factors (log rank test: p=0.02 and p<0.0001, respectively). The Cox regression model by stepwise selection confirmed lobular histological type (p=0.008; HR: 3.83, 95% CI: 1.31-11.21) and local recurrence (p<0.001; HR: 9.05, 95% CI: 3.05-26.82) as independent prognostic factors for disease specific survival. For local disease free survival, multivariate analysis did not show any significant parameters. CONCLUSION: In our series tamoxifen did not seem to improve disease specific survival and local disease specific survival. The number of events in terms of death for cancer or in terms of local recurrence is too small in this group of patients. However, according to our results we suggest not to prescribe tamoxifen in patients affected by pT1a-pT1b, pN0 breast cancer.

Nature and extent of the exposure to fibrous amphiboles in Biancavilla.

An epidemiological and environmental study in the Biancavilla area (Sicily, Italy) was recently prompted by an impressively high incidence of malignant pleural mesothelioma. Epidemiology suggested an environmental contamination by amphibole fibres rather than risks related to a specific occupational activity. The aim of this study is to describe the diffusion of fibrous amphiboles in the area and identify their source. Fibrous amphiboles were found in the products from the local quarries, which had been used for years to build houses. After sampling all around Biancavilla, three sites were detected and they were characterized by an abundant presence of mineral fibres. Fibrous amphiboles were also recovered from building materials (mortar and plasters) and airborne particulates sampled in urban sites with high dust emissions due mainly to unpaved roads. Moreover, amphibole fibres were detected in the lung tissue of a woman who died of pleural mesothelioma. The results of this study suggest that the amphibole fibre diffusion in the Biancavilla environment lasted for many years and had been maximum during the sixties and the seventies with the uncontrolled development of the local building industry. Today, the environmental situation results to be changed following both the closing of the stone quarries and the urbanization works after 2001, above all the asphalting of dusty roads. Anyway sporadic mesothelioma cases have still to be expected in the next years.

Multinucleation and pro-inflammatory cytokine release promoted by fibrous fluoro-edenite in lung epithelial A549 cells.

An unusual cluster of malignant mesothelioma was evidenced in Biancavilla, a Sicily village where no inhabitant had been significantly and professionally exposed to asbestos. Mineralogical and environmental studies led to the identification of a new prismatic amphibole, named fluoro-edenite. We previously reported, by using the human lung epithelial A549 cells, that prismatic fluoro-edenite was unable to induce changes that could be somehow related to cellular transformation, and this was in accordance with studies carried out in vivo. More recently, a fibrous amphibole with a composition very similar to that of prismatic fluoro-edenite, was identified in Biancavilla. This fibrous fluoro-edenite was shown to induce mesothelioma in rats. In keeping with this effect in vivo, in the present work we observed multinucleation and spreading, common features of transformed cells, as well as pro-inflammatory cytokine release in A549 cells. Such cell changes occurred without interfering with the passage of the resulting multinucleated cells through the cell cycle and without condemning cells to death. Hence, in lung epithelial cells, fibrous fluoro-edenite behaved similarly to the unrelated asbestos type crocidolite, whose connection with severe inflammation and cancer of the lung is renowned.

[Results of an interlaboratory fibre count comparison program concerning the SEM technique]. / Risultati di un programma pilota per il controllo di qualità dei laboratori che effettuano analisi sull'amianto mediante microscopia elettronica a scansione (SEM).

BACKGROUND: The necessity of quality control for laboratories carrying out airborne asbestos fibre monitoring is recognized in Italian law concerning the worker and the environmental protection against asbestos. The scanning electron microscopy technique is prescribed to control the airborne fibre concentration after asbestos removal from buildings. OBJECTIVES: In 2002 the Italian laboratories carrying out SEM analysis on asbestos were requested by the Istituto Superiore di Sanità to take part in a fibre count comparison program. Thirty-nine agreed to participate. METHODS: Fifteen samples were exchanged among the laboratories participating in the program. Seven samples consisted of polycarbonate membranes and eight of cellulose ester membranes. The sample loads did not exceed 50 fibres/mm2. The fibre counting results were evaluated with reference to the mean value of each sample calculated from the results provided by all the participants. RESULTS: Only 19% of the fibre count results were considered "insufficient", and the results falling within the 95% confidence interval were the 65% of the total. University and public laboratories obtained on the whole the best results.

In vitro effects on macrophages induced by noncytotoxic doses of silica particles possibly relevant to ambient exposure.

The RAW 246.7 macrophage cell line was exposed in vitro to aged crystalline silica particles of respirable size for 24 h at a range of doses starting from 15 microg/2 x 10(6) cells, which is a realistic exposure level of macrophages in the airways of ambiently exposed individuals. The particle sample used for the experiments was prepared to mimic some aspects of ambient crystalline silica particles: size distribution, morphology, and surface reactivity. Our purpose was to determine whether a nontoxic quartz load comparable to that of ambient exposure would be able to induce macrophage activation and impairment of the phagocytic ability, factors altering the lung's capacity to deal with increased particle loads (as occurs during high-pollution episodes) or infections and affecting the local and systemic responses through the release of biologically active compounds (cytokines, reactive oxygen species, NO, isoprostanes). Exposure of RAW 264.7 cells to aged silica particles induced macrophage activation (evidenced by the morphological features observed with scanning electron microscopy and by the release of TNF-alpha and IL-6) and impairment of phagocytosis of test particles, even at noncytotoxic doses. The reduction of the phagocytic function of the cells after silica treatment was dose-dependent, as evidenced by an increase of the population of unphagocytic cells, paralleled by a decrease of the actively phagocytizing cell population. We evaluated the oxidative stress induced by aged silica particles, quantifying the peroxidation products (8-isoprostanes) in the culture media of treated cells, and found a strong release at low doses. Isoprostanes are a complex family of compounds which have been used as in vivo markers of lipid peroxidation in human disorders, but that, as far as we know, have never been evaluated in relation to airborne particulate matter exposure. Lipid peroxides are involved in various cellular events in the inflammatory response, and isoprostanes are also supposed to exert important biological actions on airway and pulmonary vascular smooth muscles and on platelets.

Use of a dynamic in vitro attachment and invasion system (DIVAS) to determine influence of growth rate on invasion of respiratory epithelial cells by group B Streptococcus.

Expression of capsular polysaccharide (CPS) and some surface proteins by group B Streptococcus (GBS) is regulated by growth rate. We hypothesized that precise control of GBS growth, and thus surface-expressed components, could modulate the ability of GBS to invade eukaryotic cells. To test this hypothesis, a dynamic in vitro attachment and invasion system (DIVAS) was developed that combines the advantages of bacterial growth in continuous culture with tissue culture. Tissue culture flasks were modified with inlet and outlet ports to permit perfusion of GBS. Encapsulated type III GBS strains M781 and COH1 and strains COH1-11 and COH1-13 (transposon mutants of COH1 that express an asialo CPS or are acapsular, respectively) were grown in continuous culture in a chemically defined medium at fast mass doubling time (t(d) = 1.8 h) and slow (t(d) = 11 h) growth rates, conditions previously shown to induce and repress, respectively, type III CPS expression. Encapsulated GBS strains invaded A549 respiratory epithelial cells 20- to 700-fold better at the fast than at the slow growth rate, suggesting a role for CPS. However, unencapsulated GBS were also invasive but only when cultured at the fast growth rate, which indicates that GBS invasion is independent of CPS expression and can be regulated by growth rate. Growth rate-dependent invasion occurred when GBS was grown in continuous culture under glucose-defined, thiamine-defined, and undefined nutrient limitations. These results suggest a growth rate-dependent regulation of GBS pathogenesis and demonstrate the usefulness of DIVAS as a tool in studies of host-microbe interactions.

The two PM(2.5) (fine) and PM(2.5-10) (coarse) fractions: evidence of different biological activity.

Recent studies have shown that an increased concentration of environmental particulate matter (PM(10)) is related to many respiratory diseases. One major issue is whether the toxicity of the particles resides in some particular fraction as defined by chemical composition and size. The overall purpose of this study was to compare the in vitro toxicity of coarse (PM(2.5-10)) and fine (PM(2.5)) particulate matter, collected in an urban area of Rome, in relation to their physicochemical composition as assessed by analytic electron microscopy and atomic absorption spectroscopy. In particular, our aim was to evaluate the importance of particle physicochemical components in the induced toxicity. The in vitro toxicity assays used included human red blood cell hemolysis, cell viability, and nitric oxide (NO) release in the RAW 264.7 macrophage cell line. The hemolytic potential has been widely used as an in vitro toxicity screen and as a useful indicator of oxidative damage to biomembranes. We found that human erythrocytes underwent dose-dependent hemolysis when they were incubated with varying concentrations of fine and coarse particles. The hemolytic potential was greater for the fine particles than for the coarse particles in equal mass concentration. However, when data were expressed in terms of PM surface per volume unit of suspension, the two fractions did not show any significant hemolytic differences. This result suggested that the oxidative stress induced by PM on the cell membranes could be due mainly to the interaction between the particle surfaces and the cell membranes. RAW 264.7 macrophage cells challenged with particles showed decreased viability and an increased release of NO, a key inflammatory mediator, and both effects were not dose dependent in the tested concentration range. The fine particles were the most effective and the differences between the two size fractions in inducing these biological effects remained unchanged when the basis of comparison was changed from weight to surface measures. It seemed therefore that these differences relied on the different physicochemical nature of the particles. The main chemical difference between the two fractions resided in a greater abundance of C-rich particles with S traces in the fine fraction. Therefore, we cautiously suggest a role for these particles in the induction of toxicity.

Unusually high incidence of malignant pleural mesothelioma in a town of eastern Sicily: an epidemiological and environmental study.

In a recent epidemiological study, researchers investigated mortality from malignant pleural neoplasms in Italy, and they detected some geographic clusters of cases of this disease. We found a town located in a volcanic area of eastern Sicily to be of special interest. The residents, some of whom were diagnosed with pleural mesothelioma, had never had any relevant exposure to asbestos during their professional lives. The results of an environmental survey suggested that a possible cause of asbestos exposure was the stone quarries near the town. The products of the quarries contain fibrous amphiboles, which are used widely in the local building industry. These fibrous amphiboles were identified as intermediate phases between tremolite and actinolite. Samples were collected from buildings in the town, and concentrations of amphibole fibers were evaluated. Fibrous phases were detected in 71% of the samples, and fiber concentrations ranged from a few thousand to more than 4 x 10(4) fibers/mg of material. In addition, we conducted a study on the mineral fiber lung burden in a pleural mesothelioma case. Many mineral fibers that were classified as the same tremolite-actinolite fibrous amphibole found in the quarries and in the building materials were detected in the lung tissue. The results suggest that the inhabitants of the town we studied had been exposed for several decades to asbestos fibers that were present in the material extracted from the local stone quarries. The material was subsequently used in the building industry, and this has caused an increased risk of pleural mesothelioma in the area.

[Presence of asbestos in naval vessels: study of airborne fiber concentrations on Italian railways ferry boats]. / Presenza di amianto sulle navi: studio sulla concentrazione di fibre aerodisperse su navi traghetto delle Ferrovie dello Stato.

Asbestos has been widely used on ships as an insulating material due to its fire-resistant and sound-absorbent properties. It was therefore deemed appropriate to measure the concentrations of airborne asbestos fibres on two ferries in regular service on the Civitavecchia-Golfo Aranci route. Decontamination work had been carried out on these vessels in order to remove, as far as possible, or to confine asbestos. Between 1994 and 1998, the Ultrastructures Laboratory of the Istituto Superiore di Sanità analysed 123 samples via scanning electron microscopy (SEM) with elementary dispersion X spectroscopy (EDXS). The results showed that in 98.4% of the samples concentrations in the air were below 2 fibres/litre, which is the value set by Ministerial Decree of 6/9/94 for buildings to qualify for effective decontamination status. Concentrations above this value, between 2 and 10 fibres/litre, were found in one ferry engine room, where workers were not continuously present since a remote control box was installed there. The results show that there is no environmental dispersion of asbestos fibres in usual navigation conditions; the situation is comparable to that in buildings where asbestos-containing safety materials have been used and that are subject to period checks in accordance with the guidelines included in Ministerial Decree of 6/9/94. Legislation is deemed necessary to make law 257/92 applicable to naval vessels in order to define univocal criteria for risk evaluation, checking, maintenance and custody procedures of asbestos-insulated vessels, and procedures for each job on board involving handling or removal of asbestos-containing material.

Development of a method for the determination of low contents of asbestos fibres in bulk material.

Asbestos is a category 1 carcinogen under the EU classification, but in the absence of a method to quantify asbestos in a matrix at the 0.1% level, there has been a delay in implementing relevant directives to asbestos. An analytical scheme for identification and quantification of asbestos using polarised light microscopy (PLM) and phase contrast optical microscopy (PCM) has now been developed. When used on artificial mixtures by an experienced laboratory, it achieved the required target performance, at 0.1% asbestos concentration by mass in a bulk sample, to obtain a result, which with 90% probability, is correct within a factor of two. The method of identification by PLM and quantification by PCM has been assessed by interlaboratory comparisons. The method begins with an initial identification using PLM, and depending on asbestos type and matrix a combination of preparation procedures are used to produce the analytical filter. A gentle comminution method was used which reduces the risk of overmilling. The asbestos mass percentage on the filter is quantified using PCM in combination with a PLM attachment for identification of possible non-asbestos fibres. The final method is supported by efficient methods for fibre identification for size determination and calculation of total fibre volume. A statistical analysis of mass concentration estimates was made and the effect of preferred orientation of fibres on the analytical filter was quantified.

Asbestos lung burden and asbestosis after occupational and environmental exposure in an asbestos cement manufacturing area: a necropsy study.

OBJECTIVE: The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs). METHODS: The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4. RESULTS: Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL. CONCLUSION: The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.

[Asbestos fiber count in extra-pulmonary tissues]. / Riscontro di fibre di asbesto in tessuti extrapolmonari.

Most autoptic tissues of three men (two with pulmonary asbestosis and one without any exposure to asbestos) were analyzed by transmission electron microscopy and energy dispersion spectrometry for the quantitative and qualitative evaluation of asbestos fibers. Preliminary results indicate that only in cases with occupational exposure were found asbestos fibers (in lung, pleura , bladder, kidney and liver). These results allow interesting speculations on some environmental pathogenetic questions and deserve further investigations.

[The concentration levels of airborne quartz at an urban site]. / Livelli di concentrazione del quarzo aerodisperso in un sito urbano.

The IARC has recently included crystalline silica among substances considered carcinogenic for man. This new evaluation immediately posed the need to measure the exposure levels of the general population. The paper reports the results of measurements of the concentrations of quartz (i.e., the most common form of crystalline silica) in a location in the urban area of Rome. First we studied the respirable fractions of the airborne particles (PM10) sampled in the Spring of 1996 with a cascade impactor, which were characterized using a scanning electron microscope equipped with an X-ray microprobe. Ten components were identified including total silica (crystalline and amorphous), which was present in a percentage of 3.7% on average. On the basis of these data a methodological study was undertaken of the concentration of quartz in the historic series of PM10 sampled daily at the same site by means of an AMP instrument (Airborne Particles Monitor). The filters of mixed cellulose esters on which the PM10 was collected were incinerated at low temperature in oxygen plasma to eliminate the organic component. The residue was deposited on silver filters which were read with a conventional X-ray diffractometer in order to determine the quantity of quartz. We analyzed 28 filters from four representative weeks of the four seasons of 1994, the year in which systematic sampling was initiated. The results showed a mean weekly concentration of airborne quartz of between 0.6 and 1.5 micrograms/Nmc, which gives a percentage over PM10 of 1.7 and 3.4 respectively. These data substantially agree with previous results obtained with electron microscopy and show that the levels of quartz in the urban atmosphere under study were about one hundred times lower than the TLV currently recommended by the ACGIH for working environments (100 micrograms/Nmc) and which are also in force in Italy.

Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine.

Group B Streptococcus (GBS) is an important perinatal pathogen. Because transplacentally acquired maternal antibodies to the GBS capsular polysaccharides (CPS) confer protection, prevention of infant disease may be possible after immunization of women. Unfortunately, the purified CPS of GBS are only variably immunogenic in adults; therefore to enhance immunogenicity we have designed and developed a CPS-protein conjugate vaccine. The lability of a conformationally dependent epitope on the III CPS containing a critical sialic acid residue was important to consider in vaccine design. 100 women were randomized to receive GBS type III CPS-tetanus toxoid conjugate (III-TT) vaccine at one of three doses; unconjugated GBS type III CPS; or saline. Serum samples were obtained before immunization and 2, 4, 8, and 26 wk thereafter, and specific antibody to type III CPS was measured. Vaccines were well tolerated. In sera from recipients of the highest dose of III-TT, CPS-specific IgG levels rose from a geometric mean of 0.09 microg/ml before immunization to 4.53 microg/ml 8 wk later, whereas levels in recipients of unconjugated type III CPS rose from 0.21 microg/ml to 1.41 microg/ml. Lower doses resulted in lower antibody levels. A > or = 4-fold rise in antibody concentration was achieved in 90% of recipients of III-TT compared with 50% of those that received III CPS (P = 0.0015). Antibodies evoked by the conjugate vaccine recognized a conformationally dependent epitope of the III-CPS, promoted opsonophagocytosis and killing of GBS, and, after maternal immunization, protected neonatal mice from lethal challenge with type III GBS. We conclude that directed coupling of type III GBS polysaccharide to a carrier protein yielded a conjugate vaccine with preserved expression of a highly labile conformational epitope involving sialic acid and enhanced immunogenicity compared with uncoupled CPS.

[The determination of asbestos fiber concentration by scanning electron microscopy: a comparison of the results obtained by different laboratories]. / Determinazione della concentrazione di fibre di amianto mediante microscopia elettronica a scansione: confronto dei risultati ottenuti da laboratori diversi.

Recently the use of scanning electron microscopy to evaluate asbestos fibre concentration in the environment has been prescribed by national law. So far data on the correlatability of results provided by different laboratories are not available. In the present study 55% of results obtained by the participants was in the range of +/- 30% of the mean and 90% in the range of +/- 50%. One of the main factors causing variability of results turned out to be related to the behaviour of technicians.