Reconstructing historical exposure to asbestos: the validation of 'educated guesses'.

BACKGROUND: In both the epidemiological and legal context, the causal attribution of asbestos-related lung diseases requires retrospective exposure assessment (REA). AIMS: To assess the correlation between the retrospective assessment of occupational and anthropogenic environmental exposure to asbestos and its content in the lung tissue. METHODS: Based on the available exposure information, a team of occupational physicians retrospectively assessed cumulative exposure to asbestos in 24 subjects who died of asbestos-related diseases. The asbestos lung content was analysed using analytical scanning electron microscope (SEM-EDS). The Log10 asbestos fibre count in the autoptic samples was predicted as a function of the Log10 estimated cumulative exposure using univariate regression analysis. RESULTS: The median count of asbestos fibres by grams of dry weight (ff/gdw) in the lung tissue was 81 339 (range 0-2 135 849.06); it was 287 144 (range 0-2 135 849.06) among the occupationally exposed, and 29 671 (range 0-116 891) among the subjects who only had anthropogenic environmental and/or household exposure. Amphiboles, and particularly amosite (52%) and crocidolite (43%), were detected in all the study subjects. Chrysotile was not detected in any of the samples. Overall, the retrospective estimate of lifetime cumulative exposure to asbestos showed a moderate correlation with the total asbestos fibre count in the autoptic lung, with the regression model explaining 38-55% of the total variance. CONCLUSIONS: Detailed information on occupational, environmental and household exposure circumstances would be indispensable for experienced industrial hygienists and/or occupational physicians to reliably assess past exposure to amphiboles or mixed types of asbestos.

Occupational low-level exposure to hard metals: cobalt and tungsten biomonitoring as an effective tool to evaluate the effectiveness of industrial hygiene interventions for risk management.

Purpose: The aim of the study was to assess the exposure to Cobalt (Co) and Tungsten (W) in a group of hard metal tool sharpeners through a combined approach of air and biological monitoring, and to evaluate the effectiveness of a control and improvement intervention carried out in collaboration with the medical officers of the local Health Protection Agency, by biomonitoring.Methods: We enrolled 132 workers from 17 companies of the province of Brescia, northern Italy. The study was performed in two phases: (1) an environmental and biomonitoring survey to assess the workers' exposure to Co and W at their usual working conditions; (2) a further biomonitoring survey 3 months after the enforcement of a control and improvement intervention, to assess its effectiveness.Results: Workers were found to be exposed to low concentration of airborne dust containing Co and W but after the intervention we recorded a significant decrease of the urinary concentrations of both Co and W. The extent of the decrease was correlated to the number of preventive industrial hygiene interventions that were carried out.Conclusions: Biological monitoring of Co and W in the hard metal tools manufacturing industry is a sensitive and effective method to evaluate the effectiveness of prevention practices.

[Primary treatment for localized prostate cancer: evaluation of patients' quality of life]. / Patienten nach Primärtherapie eines klinisch lokal begrenzten Prostatakarzinoms: Evaluation der Lebensqualität.

BACKGROUND: Radical prostatectomy (RP) and percutaneous radiotherapy (RT) are viable options for the primary treatment of localized prostate cancer (PC). Given the comparable efficacy of both modalities quality of life (QOL) has been suggested as an additional decision criterion. In recent years several validated instruments have been introduced to assess QOL. Most of them allow for patient-based rating of QOL. AIM: Herein, we aim to compare QOL after RP and RT in our own cohort of patients in Tübingen using validated questionnaires. METHODS: In total, 165 patients who had been treated for PC in Tübingen were enrolled. Of those 100 men had RP and 65 had RT. The validated QOL questionnaires EORTC QLQ-C30 and EORTC QLQ-PR 25 were used for assessment. Statistical analyses focused on analyses of variance. RESULTS: Concordant to previous studies it could be shown that RP mainly creates voiding problems most importantly urinary incontinence but also erectile dysfunction. After RT, patients mainly complained about disturbed bowel function including diarrhea and proctitis as well as about urgency and frequency. RP patients had better PF2 Scale values than RT patients (p= 0.00357143). On DI scales RT patients yielded significantly poorer values than the RP group (p= 0.003333). CONCLUSION: Our data comply well with those from other international centers. QOL is an important yet underestimated variable in oncological research. Our investigations underline the importance of an interdisciplinary approach for the successful management of PC.

Comparison of pharmacokinetic profiles of a 17 beta-estradiol gel 0.6 mg/g (Gelestra) with a transdermal delivery system (Estraderm TTS 50) in postmenopausal women at steady state.

OBJECTIVES: to compare the patterns of a 17 beta-estradiol (E(2)) gel containing 0.6 mg/g (1.5 mg E(2) per day, Gelestra); with the transdermal delivery system (Estraderm TTS 50) applied every 3 days over a 14-day period to women in spontaneous or surgical menopause. METHODS: a single centre, open, randomised, parallel-group study was conducted. A total number of 33 postmenopausal women were enrolled. In 23 of them the menopause occurred spontaneously, while 10 women were bilaterally ovariectomized. Randomly, the subjects were treated with Estraderm TTS 50 (no. 8) or with Gelestra (no. 14). The pharmacokinetic study of the drugs was performed at the seventh, ninth and 14th day in Gelestra treated women and at the first, third and second day in Estraderm TTS 50 treated women. In fact, the seventh, ninth and 14th day of percutaneous treatment corresponds to the first, third and second day of application of the transdermal system application. Blood samples were taken by each subject at baseline and 1, 2, 3, 4, 8, 12 and 24 h after the gel or transdermal system application. In almost all samples the level of E(2) and estrone (E(1)) were evaluated. Statistical analysis was performed by comparing the two groups of treatment. The following parameters were assessed: mean E(2) and E(1) concentrations, E(2) peak serum concentration within interval from 0 to 72 h (C(max)), E(2) trough concentration within interval from 0 to 72 h (C(min)), area under the E(2) time concentration curve in the interval from 0 to 72 h (AUC((0-72))), the average E(2) concentration during the measurement interval, calculated by dividing AUC((0-72)) by 72 h (C(av)), E(1)/E(2) ratio, and percentage fluctuation (%Fluct) which is equal to 100 (C(max)-C(min)/C(max)). RESULTS: there was no significant difference in E(2) C(av) between the two treatments. However, significant differences in favour to the gel on the first day (first h) and on third day (72nd h) and in favour to the patch at the second day (48th h) were detected. C(max), E(1)/E(2) ratio and AUC((0-72)) were not statistically different, while a significantly higher C(min) for the gel was observed. Furthermore, the 90% confidence interval for AUC((0-72)) ratio (0.83-1.10) was within the commonly applied bioequivalence acceptance range (0.80-1.25). The %Fluct was significantly lower for Gelestra than for Estraderm TTS 50. CONCLUSIONS: although the mean E(2) and E(1)concentrations, C(max), E(1)/E(2) ratio and the AUC((0-72)) did not differ between the two E(2) treatments, the Gelestra treatment showed a lower day-to-day variation over the three day application, than the Estraderm TTS 50.

Influence of vaginal danazol on uterine and brain perfusion during hormonal replacement therapy.

OBJECTIVE: To evaluate the effectiveness of vaginal danazol as progestin supplement to estrogen replacement therapy, and its interference with uterine and carotid artery flow compared with medroxyprogesterone-acetate (MPA), estrogen alone, and placebo. METHODS: Forty healthy women at least 12 months after natural menopause were randomly divided into four treatment groups: Group 1 (n=10), continuous transdermal estradiol (TE) (50 microg/day), plus a monthly 10-day course of MPA (10 mg/day); Group 2 (n=10), continuous TE plus a monthly 10-day course of vaginal danazol (200 mg/day); Group 3 (n=10), TE alone; Group 4 (n=10), placebo. At baseline and during the first, third, and sixth month of treatment, the endometrial thickness was assessed by transvaginal ultrasonography, while the pulsatility index (PI) of the carotid and uterine arteries was assessed by color Doppler. An endometrial biopsy was also performed before and after the treatment. RESULTS: At baseline, no significant differences between ages and other evaluated parameters were present in the four groups. In groups 1, 2, and 3, the values of carotid and uterine PI decreased significantly and similarly during the treatment, while in group 4 they were unchanged. In group 3 only, the endometrium was significantly thicker during treatment than before. No endometrial hyperplasia was present in the four groups at the end of the treatment. CONCLUSIONS: Vaginal danazol seems to be capable of counteracting the mitogenic effect of estrogen on the endometrium without reducing the effectiveness of estrogens to improve peripheral arterial perfusion.

Effects of acute administration of natural progesterone on peripheral vascular responsiveness in healthy postmenopausal women.

Peripheral vascular responses to acute administration of natural progesterone were studied in 12 postmenopausal women (mean +/- SD age 50.3 +/- 4.8 years) with no evidence of cardiovascular disease. According to a randomized, double-blind protocol, all subjects were given natural progesterone as a vaginal cream, able to produce a rapid peak and decay of plasma hormone concentrations, or matched placebo, with crossover after a 1-week washout period. Forearm blood flow and peak flow after ischemic stress (ml/100 ml/min), local vascular resistance (mm Hg/ml/100 ml/min), venous volume (ml/100 ml), and venous compliance (ml/100 ml/mm Hg) were measured by strain-gauge venous occlusion plethysmography at baseline and after progesterone or placebo administration. Plasma norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection. Progesterone sharply decreased forearm blood flow (p <0.01) through an increase in local vascular resistance (p <0.01). Measures of venous function remained unchanged. Although the hormone increased circulating norepinephrine concentrations (p <0.05), there were no significant changes in mean arterial pressure or heart rate. Furthermore, progesterone reduced the local vasodilator capacity, shown by a decrease in forearm delta flow (difference between peak flow and basal flow, p <0.05). Compared with the well-known effect of estrogen, progesterone exerted an opposite action on peripheral vascular responsiveness. Peripheral circulatory changes may be attributed to a direct activity of progesterone on the arterial wall and may in part reflect a modulation of the hormone on peripheral sympathetic tone. Consideration must be given to the hypothesis that the addition of progestin may attenuate the beneficial effects of unopposed estrogen replacement therapy in postmenopausal women.

Estradiol-17beta reduces blood pressure and restores the normal amplitude of the circadian blood pressure rhythm in postmenopausal hypertension.

After menopause, both systolic (SBP) and diastolic (DBP) blood pressure (BP) become higher in women than in men of the same age, suggesting that estrogen deficiency may influence the age-related increase in BP. We studied 30 postmenopausal women (mean age, 55 +/- 5.7 years; time from menopause, 2-5 years) affected by mild hypertension with no target-organ complications by means of 24-h BP monitoring. None of the group were undergoing estrogen replacement therapy or taking antihypertensive drugs. According to a randomized, double-blind protocol, subjects received patches of transdermal estradiol-17beta (E2) or a matched placebo, with crossover after a 7-day washout period. In 12 patients the 24-h peak-to-trough variation in SBP and DBP amounted to less than 10% (nondippers). Administration of E2 significantly decreased 24-h SBP and DBP in the whole cohort (P < .05). Furthermore, E2 restored the expected reduction in BP during nighttime in the nondipper subgroup. It is well known that estrogen replacement therapy protects against the development of both cardiovascular diseases and stroke. Our data suggest that this activity could be attributed, at least in part, to the activity of E2 in preserving physiologic circadian fluctuation of BP.

Effects of acute administration of transdermal estrogen on postmenopausal women with systemic hypertension.

We studied 16 postmenopausal women with mild to moderate hypertension according to a randomized, double-blind protocol. They received patches of transdermal estradiol-17beta rated to deliver 100 mg/day of substance or matched placebo. A 24-hour ambulatory blood pressure (BP) monitoring was performed at baseline and after drug administrations. Our data show that estradiol-17beta exerts beneficial effects, both in lowering elevated BP levels and in maintaining a uniform BP control over 24 hours. Estrogen replacement therapy could be considered when significant changes in BP occur during the postmenopausal period.