Vaginal atrophy across the menopausal age: results from the ANGEL study.

OBJECTIVES: This study aimed to investigate the prevalence of vaginal atrophy (VA) in women across the menopausal age. METHODS: A multicenter cross-sectional investigation was performed on 747 females, 40-55 years of age, in 30 outpatient public services across the nation. The VA diagnosis was based on the combination of patient sensation of vaginal dryness, an objective sign of VA, and pH >5. RESULTS: VA was diagnosed in 36.8% of women. Prevalence ranged from 19.2% (40-45 year olds) to 53.8% (52-55 year olds). pH >5 (37.5%) was less prevalent than isolated VA symptoms or signs. Vaginal dryness (64.0%) was the most prevalent symptom followed by dyspareunia (54.5%), itching (38.5%) burning (38.3%), and dysuria (28.9%). Prevalence of vaginal signs declined from vaginal dryness (60.3%) to vaginal thinning (54.5%), vaginal pallor (47.4%), presence of petecchiae (15.7%), and mucosa fragility (15.1%). Most signs and symptoms showed an age-related increase in frequency and intensity. VA was independently associated (R2 = 0.139; p < 0.0001) with age (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.03-1.13), being in postmenopause (OR 3.45; 95% CI 2.29-5.19), and presence of vasomotor symptoms (OR 3.10; 95% CI 2.09-4.60). CONCLUSION: VA and its symptoms are common in women across the menopausal age. VA identification may favor early management and treatment.

Exposure to brominated and organophosphate ester flame retardants in U.S. childcare environments: Effect of removal of flame-retarded nap mats on indoor levels.

We assessed exposure to 39 brominated and 16 organophosphate ester flame retardants (FRs) from both dust and indoor air at seven childcare centres in Seattle, USA, and investigated the importance of nap mats as a source of these chemicals. Many childcare centres serving young children use polyurethane foam mats for the children's naptime. Until recently, the vast majority of these mats sold in the United States contained flame-retarded polyurethane foam to meet California Technical Bulletin 117 (TB117) requirements. With the 2013 update of TB117, allowing manufacturers to meet flammability standards without adding FRs to filling materials, FR-free nap mats have become widely available. We conducted an intervention study by actively switching out FR-treated nap mats with FR-free nap mats and measuring FR levels in indoor air and dust before and after the switch-out. The predominant FRs found in dust and indoor air were 2-ethylhexyl tetrabromobenzoate (EHTBB) and tris(1-chloro-2-propyl) phosphate (TCIPP), respectively. Nap mat samples analysed from four of the six centres contained a Firemaster® mixture, while one mat was predominantly treated with tris(1,3-dichloroisopropyl) phosphate (TDCIPP) and the other contained no detectable target FRs. After replacement, there was a significant decrease (p = 0.03-0.09) in median dust concentrations for bis(2-ethylhexyl) tetrabromophthalate (BEHTBP), EHTBB, tris(4-butylphenyl) phosphate (TBPP), and TDCIPP with reductions of 90%, 79%, 65%, and 42%, respectively. These findings suggest that the nap mats were an important source of these FRs to dust in the investigated childcare environments and that a campaign of swapping out flame-retarded mats for FR-free ones would reduce exposure to these chemicals. While calculated exposure estimates to the investigated FRs via inhalation, dust ingestion, and dermal absorption were below established reference dose values, they are likely underestimated when considering the toddlers' direct contact to the mats and personal cloud effects.

Penetration of benzene, toluene and xylenes contained in gasolines through human abdominal skin in vitro.

Few studies are available in literature on the risk for humans from skin exposure to gasolines. This work is focused on the in vitro skin penetration of benzene (carcinogenic substance), toluene and xylenes. We examined three commercial gasolines using the Franz diffusion cells and human abdominal full thickness skin. Gasoline composition was determined using a multi-dimensional gas chromatographic (MDGC) technique. Aromatic compounds into the receptor fluid, consisting of saline solution were quantitated by a gas chromatography technique equipped with a flame ionization detector (GC-FID) and coupled with a headspace-solid phase micro extraction system (HS-SPME). Among the three substances, benzene showed the highest average apparent permeability coefficient (K(p)=43.8x10(-5)cmh(-1)) compared to toluene (K(p)=6.48x10(-5)cmh(-1)) and xylenes (K(p)=0.84x10(-5)cmh(-1)). This value could be explained by the lower boiling point and higher water solubility of benzene. Lag times were about 1h for benzene and 2h for toluene and xylenes. Averaged total recoveries in the receptor fluid were 0.43% of dose for benzene, 0.06% for toluene and 0.008% for xylenes. A statistical significative difference (Student's t-test, P<0.05) between the fluxes calculated for the three gasolines are noted only for xylene and for toluene between gasolines #1 (richer in aromatic compounds) and #3. The obtained apparent permeability coefficient are useful for determining the permeability of these aromatics components from gasolines of a different composition. Hands exposure risk, calculated using RfD and RfC as defined by US EPA, is critical for benzene. The risk of skin permeation of gasoline, and, in particular, of benzene, should be better evaluated for those workers who have a large potential for exposure. Adequate personal protective equipment should be used in the high exposure jobs, mainly for hands and forearms.

Percutaneous absorption of 5 glycol ethers through human skin in vitro.

Absorption across full thickness human skin was evaluated in vitro for five selected glycol ethers. Skin membranes were settled on static diffusion cells and both neat and 50% water diluted glycol ethers were applied on the donor chamber for 8 h. The amount of glycol ethers permeated into the receptor fluid was measured by gas chromatograph equipped with flame ionization detector (GC-FID). For neat solvents, permeation coefficient Kp ranged from 0.06 to 0.83 cm h(-1) 10(-3) respectively for DEGBEA and EGMEA while for 50% v/v diluted glycol ethers it varied from 0.08 to 1.81 cm h(-1) 10(-3) respectively for DPGME and EGMEA. These experiments show a statistically significant (Student's t-test, P <0.05) increase in permeation coefficients from neat to 50% water diluted glycol ethers and the same trend can be observed in fluxes and lag times. Only DPGME show an opposite behaviour. These results confirm the good ability of these solvents of permeating the skin and show that they could represent a risk for their potential dermal absorption both for workers and for occasional exposures, since the average lag time is 1.57 h.

Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma: a pilot study.

BACKGROUND: The authors have developed a new method of drug delivery into the brain using implantable biodegradable microspheres. In this study, this method was used to provide localized and sustained delivery of 5-fluorouracil (5-FU) after the surgical resection of glioblastoma. This antimetabolite and radiosensitizing drug was selected in an attempt to decrease the rate of local recurrence of the tumor. METHODS: Eight patients with newly diagnosed glioblastoma were included in the study and 2 increasing amounts of 5-FU were studied (70 mg and 132 mg). After surgical resection of the tumor, poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres with an average dimension of 45 microm were implanted in the wall of the surgical bed. External beam radiation (59.4 grays) was initiated before the seventh postsurgical day. Patients were followed by clinical examination, magnetic resonance imaging, and 5-FU assays in the blood and cerebrospinal fluid (CSF). RESULTS: 5-FU assays confirmed sustained concentrations in the CSF for at least 1 month. Concentrations of 5-FU in the blood were lower and transitory. Systemic tolerance to the treatment was good; one case of recurrent brain swelling was observed at the higher dose studied. At the time of last follow-up the overall median survival time was 98 weeks from the time of implantation and 2 patients had achieved disease remission at 139 and 153 weeks, respectively. CONCLUSIONS: This study demonstrates that biodegradable microspheres are efficient systems for drug delivery into the brain and may have future application in the treatment of brain tumors. Further studies are needed to confirm the potential of 5-FU-loaded microspheres for the radiosensitization of glioblastoma. [Please see editorial on pages 197-9, this issue].