Effect of oestriol gel on dyspareunia in postmenopausal women in 2 weeks of treatment: a pilot study.

This brief report evaluates the early effect of ultra-low dose 0.005% oestriol vaginal gel on dyspareunia in postmenopausal women within the first 2 weeks of treatment. This was a prospective and multicentre single-arm pilot study and the effect of the treatment on dyspareunia was evaluated by using a diary. In total 23 women and 150 coitus were studied. 8 coitus were painless in the first week and 42 during the second week (p < .0001). A reduction in pain from the baseline was seen in 116 (77.3%) out of the 150 coitus. 0.005% oestriol vaginal gel produced a rapid and progressive improvement in dyspareunia from the very first days of treatment in postmenopausal women.IMPACT STATEMENTWhat is already known on this subject? Local oestrogen therapy has shown efficacy in the treatment of genitourinary syndrome of menopause (GSM) and dyspareunia when used for a duration of greater than 3 weeks.What do the results of this study add? This study shows that the use of oestriol gel produces clinical effects from the beginning of its use, decreasing dyspareunia in postmenopausal women within just 14 days of daily use.What are the implications of these findings for clinical practice and/or further research? In cases of dyspareunia in relation to menopause, therapy with local oestrogens, in our case oestriol gel, produces an improvement from the beginning of its use. This information is clinically relevant when evaluating therapeutic options.

MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells.

Upon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good resolution (M-MΦ) of the inflammatory process. The functional activity of polarized MΦ is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MΦ that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the MΦ secretome involved in the shedding of soluble endoglin. We find that the GM-MΦ secretome contains metalloprotease 12 (MMP-12), a GM-MΦ specific marker that may account for the anti-angiogenic activity of the GM-MΦ secretome. Cell surface endoglin is present in both GM-MΦ and M-MΦ, but soluble endoglin is only detected in GM-MΦ culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MΦ and endothelial cells. These data demonstrate a direct correlation between GM-MΦ polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.

Defining a Standard Set of Patient-Reported Outcomes for Patients With Advanced Ovarian Cancer.

Purpose: Advanced ovarian cancer (AOC) and its treatment cause several symptoms and impact on patients' health-related quality of life (HRQoL). We aim to reach a consensus on the most relevant patient-reported outcome (PROs), the corresponding measures (PROMs), and measurement frequency during AOC patients' follow-up from patients' and healthcare professionals' (HCP) perspective. Methods: The project comprised five steps: 1) a literature review, 2) a focus group with patients, 3) a nominal group with HCP, 4) two round-Delphi consultations with patients and HCP, and 5) a final meeting with HCP. Delphi questionnaire was elaborated based on literature review, focus group (n=5 patients), and nominal group (n=16 HCP). The relevance of each PRO and the appropriateness (A) and feasibility (F) of the proposed PROM were assessed (Likert scale 1=strongly agree; 9=strongly disagree). The consensus was reached when at least 75% of the panelists rated it as 'relevant', 'appropriate', or 'feasible' (score 7-9). Results: A total of 56 HCP [51.8% Hospital Pharmacy; 41.1% Oncology; 3.6% Nursing; and 3.6% Psycho-oncology; mean time in specialty 12.5 (8.0) years] and 10 AOC patients [mean time diagnosis 5.4 (3.0) years] participated in the 1st round. All PROs achieved consensus regarding their relevance, except dry skin (58.0%). Agreement was reached for PRO-CTCAE to be used to assess fatigue (A:84.9%; F:75.8%), neuropathy (A:92.4%; F:77.3%), diarrhea (A:87.9%; F:88.7%), constipation (A:86.4%; F:75.8%), nausea (A:89.4%; F:75.8%), insomnia (A:81.8%; F:88.7%), abdominal bloating (A:82.2%; F:82.2%) and sexuality (A:78.8%; F:88.6%); EQ-5D to determine patients' HRQoL (A:87.9%; F:80.3%), pain (A:87.9%; F:75.8%) and mood (A:77.7%; F:85.5%); to assess treatment adherence the Morisky-Green (A:90.9%; F:84.9%) and the dispensing register (A:80.3%; F:80.3%) were chosen. It was agreed to note in the medical record whether the patient's treatment preferences had been considered during decision-making (A:78.8%; F:78.8%) and to use a 5-point Likert scale to assess treatment satisfaction (A:86.4%; F:86.4%). Panelists agreed (A:92.4%; F: 77.3%) to collect these PROs (1) at the time of diagnosis/relapse; (2) one month after starting treatment/change therapeutic strategy; (3) every three months during the 1st-year of treatment; and later (4) every six months until treatment completion/change. Conclusions: The consensus reached represents the first step towards including the patient's perspective in AOC follow-up. The standardized collection of PROs in clinical practice may contribute to optimizing the follow-up of these patients and thus improving the quality of care.

Early natural killer cell counts in blood predict mortality in severe sepsis.

INTRODUCTION: Host immunity should play a principal role in determining both the outcome and recovery of patients with sepsis that originated from a microbial infection. Quantification of the levels of key elements of the immune response could have a prognostic value in this disease. METHODS: In an attempt to evaluate the quantitative changes in the status of immunocompetence in severe sepsis over time and its potential influence on clinical outcome, we monitored the evolution of immunoglobulins (Igs) (IgG, IgA and IgM), complement factors (C3 and C4) and lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells (CD19+) and natural killer (NK) cells (CD3-CD16+CD56+)) in the blood of 50 patients with severe sepsis or septic shock at day 1, day 3 and day 10 following admission to the ICU. RESULTS: Twenty-one patients died, ten of whom died within the 72 hours following admission to the ICU. The most frequent cause of death (n = 12) was multiorgan dysfunction syndrome. At day 1, survivors showed significantly higher levels of IgG and C4 than those who ultimately died. On the contrary, NK cell levels were significantly higher in the patients who died. Survivors exhibited a progressive increase from day 1 to day 10 on most of the immunological parameters evaluated (IgG, IgA, IgM, C3, CD4+, CD8+ T cells and NK cells). Multivariate Cox regression analysis, including age, sex, APACHE II score, severe sepsis or septic shock status and each one of the immunological parameters showed that NK cell counts at day 1 were independently associated with increased risk of death at 28 days (hazard ratio = 3.34, 95% CI = 1.29 to 8.64; P = 0.013). Analysis of survival curves provided evidence that levels of NK cells at day 1 (> 83 cells/mm³) were associated with early mortality. CONCLUSIONS: Our results demonstrate the prognostic role of NK cells in severe sepsis and provide evidence for a direct association of early counts of these cells in blood with mortality.

Real-world effectiveness and tolerability of Zelesse cream® for treating vulvovaginitis in adult women: an observational, prospective study.

OBJECTIVE: To assess the efficacy, acceptability, and tolerability of a vaginal cream based on plant extracts for treating signs and symptoms of vulvovaginitis (VV) (Zelesse cream®), either as monotherapy (non-infectious VV) or adjuvant to antimicrobial therapy (infectious VV). METHODS: This prospective, observational, multicenter study included women who attended outpatient offices for VV. The severity of signs (vaginal discharge, erythema, and edema) and symptoms (pruritus, burning, and dysuria) was assessed before and after 15±5 days of daily treatment with Zelesse cream on a 4-point scale (18-point global score). RESULTS: The study included 58 women aged 43.0±13.2 years, including 42 who were treated with Zelesse cream only and 16 who used Zelesse cream as adjuvant to antimicrobial therapy. All participants showed significantly reduced scores and absolute prevalence of individual signs and symptoms in both groups. Similarly, the median signs/symptoms decreased by 4.0 and 8.0 points in women using Zelesse only and those using Zelesse plus antimicrobial therapy, respectively. This product was well tolerated and had high acceptability. CONCLUSIONS: Zelesse cream relieves signs and symptoms of VV, either as monotherapy in non-infectious VV or as adjuvant to antimicrobial therapy in infectious VV. Future randomized, placebo-controlled trials with larger sample sizes are warranted.

Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves' disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial.

BACKGROUND: Currently, both the American Thyroid Association and the European Thyroid Association recommend preoperative preparation with Lugol's Solution (LS) for patients undergoing thyroidectomy for Graves' Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to provide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidectomy for GD. METHODS: A multicenter randomized controlled trial will be performed. Patients ≥18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery.Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoperative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS. CONCLUSIONS: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this setting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03980132.

Acceptability, tolerability, and effects on symptoms and signs of vulvovaginitis of a non-soap, herbal-based intimate hygiene solution (Zelesse®).

OBJECTIVE: To evaluate the acceptability, tolerability, and effects on vulvovaginitis symptoms and signs of a non-soap, herbal-based intimate solution (Zelesse®). METHODS: We conducted a prospective, observational, multicenter study including adult women with symptoms and signs of vulvovaginitis with various etiologies, including candidiasis, trichomoniasis, bacterial vaginosis, and atrophic and irritative vaginitis. The presence and intensity of signs (edema, erythema, vaginal discharge) and symptoms (pruritus) of vulvovaginitis were evaluated before and after 5-15 days of daily use of Zelesse® alone or as a coadjuvant in antimicrobial therapy. Variables following a normal distribution and categorical variables were analyzed using the Student t-test and chi-square or Fisher's exact test, respectively. RESULTS: A total 137 women were enrolled in the study; 87 (63.5%) women received concomitant antimicrobials and 50 (36.5%) used Zelesse® only. Global symptom scores and frequency of patients with vulvovaginitis signs and symptoms, and their mean intensity, decreased after treatment in both patient groups. Vaginal pH and (in the Zelesse®-only group) vaginal flora remained unaltered. The product was safe, well tolerated, and highly accepted by patients. CONCLUSIONS: Zelesse®, the non-soap herbal-based solution in this study, may represent a safe and effective option for symptomatic relief of vulvovaginitis.

Clinical results in the management of Frey's syndrome with injections of Botulinum toxin.

INTRODUCTION: Frey's Syndrome is defined by facial hyperhidrosis in the preauricular region unleashed by gustatory stimulus and caused mainly by parotidectomy. Several treatment and prevention measures have been proposed, with no conclusive results. Recently, injections of Botulinum Toxin have been suggested, obtaining encouraging results. The objective is to describe our experience in treating Frey's Syndrome with this drug. MATERIALS AND METHOD: Between 2004 and 2007, our team treated 10 patients suffering from Frey's Syndrome. All cases were caused by parotid resection. In 60%of cases a complete elevation of the SMAS (superficial musculoaponeurotic system) was carried out. In the remaining cases, such elevation was either not made or the SMAS was severely damaged. All patients were treated with intradermic injections of Botulinum Toxin. Recorded data were: units administered, affected area, time lapse until improvement in the symptoms, and the evolution after one, six and twelve months after the injection. Possible side effects were also recorded. RESULTS: The average treated area per patient was 26 cm2. An average of 38 units of Botulinum Toxin per patient was injected. Average time lapse until improvement was 5.5 days. Five patients were injected with a second dose after an average of 18 months from the first injection. On this occasion, the area affected was considerably smaller than that presented before the first injection. The most frequently reported side effect was dry mouth. CONCLUSION: Our team considers that treating Frey's Syndrome with Botulinum Toxin is effective. The effects of the treatment are long-lasting and side effects are minimal and temporary. A second injection is needed after 15 to 18 months of the first, although the affected area is usually smaller.

Efficacy, acceptability and tolerability of Zelesse® for the treatment of non-specific vulvovaginitis in paediatric patients: The NINESSE Study.

Objective To evaluate the efficacy, tolerability and acceptability of Zelesse®, an intimate hygiene wash solution, in the relief of the symptoms and signs of non-specific vulvovaginitis in paediatric patients. Methods The NINESSE Study was a prospective, observational, multicentre study involving females aged 2-8 years who attended paediatric offices with symptoms suggestive of non-specific vulvovaginitis. They were administered Zelesse® as a single treatment for 15 ± 5 days. Pruritus, burning, dysuria, erythema, leucorrhoea and oedema were evaluated before and after treatment. Results A total of 71 paediatric patients were enrolled in the study (mean ± SD age, 4.5 ± 1.9 years). The most significant effects were observed for pruritus and burning, where 98.4% (62 of 63) and 96.9% (63 of 65) of the patients improved after treatment, respectively. Zelesse® demonstrated a beneficial effect on dysuria, erythema, leucorrhoea and oedema. The effects on the symptoms and signs were observed within the first week of treatment; although 44.9% (31 of 69) of patients experienced improvements after 2-3 days. Zelesse® was well accepted and tolerated by most patients. No serious adverse events were reported. Conclusions Zelesse® was very effective for the relief of the symptoms and signs of non-specific vulvovaginitis, in particular pruritus, burning and erythema, in females aged 2-8 years.

Assessment of the quality of sample labelling for clinical research.

OBJECTIVE: To assess the quality of the labels for clinical trial samples through current regulations, and to analyze its potential correlation with the specific characteristics of each sample. METHOD: A transversal multicenter study where the clinical trial samples from two third level hospitals were analyzed. The eleven items from Directive 2003/94/EC, as well as the name of the clinical trial and the dose on the label cover, were considered variables for labelling quality. The influence of the characteristics of each sample on labelling quality was also analyzed. OUTCOME: The study included 503 samples from 220 clinical trials. The mean quality of labelling, understood as the proportion of items from Appendix 13, was of 91.9%. Out of these, 6.6% did not include the name of the sample in the outer face of the label, while in 9.7% the dose was missing. The samples with clinical trial-type samples presented a higher quality (p < 0.049), blinding reduced their quality (p = 0.017), and identification by kit number or by patient increased it (p < 0.01). The promoter was the variable which introduced the highest variability into the analysis. CONCLUSIONS: The mean quality of labelling is adequate in the majority of clinical trial samples. The lack of essential information in some samples, such as the clinical trial code and the period of validity, is alarming and might be the potential source for dispensing or administration errors.

Objetivo: Evaluar la calidad de las etiquetas de muestras para ensayos clínicos mediante la normativa vigente y analizar su posible correlación con las características específicas de cada muestra. Método: Estudio transversal multicéntrico en el que se analizaron las muestras de ensayos clínicos de dos hospitales de tercer nivel. Se estudió la presencia de los once ítems de la Directiva 2003/94/CE, el nombre del ensayo y la dosis en la portada de la etiqueta como variables de calidad del etiquetado. Se analizó la influencia de las características propias de la muestra con la calidad del etiquetado. Resultado: Se analizaron un total de 503 muestras de 220 ensayos. La calidad media del etiquetado, entendido como el porcentaje de ítems del Anexo 13, fue del 91,9%. El 6,6% no contenía el nombre de la muestra en la cara externa de la etiqueta, mientras que a un 9,7% les faltaba la dosis. Las muestras con presentación de tipo ensayo clínico presentaron mayor calidad (p < 0,049), el enmascaramiento disminuía la calidad (p = 0,017) y la identificación por número de kit o por paciente la aumentaban (p < 0,01). La variable promotor fue la que más variabilidad introdujo en el análisis. Conclusiones: La calidad media del etiquetado es adecuada en la mayoría de las muestras del ensayo clínico. Resulta preocupante la ausencia de información esencial, como el código del ensayo clínico y el período de validez, en algunas muestras que pueden ser fuente potencial de errores de dispensación o de administración.

Interleukin 28B rs12979860 (CT/TT) genotype is associated with milder hepatic damage in the natural evolution of HCV/HIV coinfection.

Hepatitis C virus (HCV)/human immunodefficiency virus (HIV) coinfection is a major health problem, affecting mostly to individuals with exposure to blood products, as hemophiliacs or intravenous drug users, or those exposed to high-risk sexual practices. Genotyping of interleukin 28B (IL-28B) rs12979860 polymorphism is a useful tool for guiding therapeutic decisions in this disease. On the contrary, there is not enough information on the pathogenic role of this polymorphism in the natural history of the disease. The objective of this study is to describe the relationships between the CT/TT genotype of this polymorphism with viral loads and also with a number of biomarkers of liver function in coinfected patients naïve for treatment for HCV. Seventy-five HCV/HIV coinfected patients were retrospectively recruited in our Hospital from 2010 to 2011. Logistic regression analysis adjusting by [Age], [Sex], [HCV viral genotype], [HCV viral load], [HIV viral load], and [CD4 T cells levels] revealed the IL-28B rs12979860 (CT/TT) genotype as a protective factor against alanine aminotransferase (ALT) levels (>100 IU/L), aspartate aminotransferase (AST) levels (>75 IU/L), and AST-to-platelet ratio index (APRI) score for liver fibrosis (>1.5) [OR, (95% CI), p]: ALT [0.026 (0.001-0.576) 0.021]; AST [0.001 (0.000-0.297) 0.019]; APRI [0.031 (0.002-0.41) 0.008]. Stepwise regression analysis considering the same adjusting variables showed the same results. In consequence, the IL-28B rs12979860 (CT/TT) genotype, which is a marker of poor response to HCV treatment, could be mediating on the contrary a certain protective effect against the hepatic damage caused by this virus in patients coinfected by HIV.

Early levels in blood of immunoglobulin M and natural killer cells predict outcome in nonseptic critically ill patients.

PURPOSE: Critical illness results in derangements of all components of the immune response. Nonetheless, most of the efforts evaluating immune status in critically ill patients have been done in the field of sepsis. Here we have evaluated the immunity status at intensive care unit (ICU) admission in a cohort of nonseptic critically ill patients and its influence on their outcome. MATERIAL AND METHODS: Ninety patients 18 years and older admitted to our ICU were studied for levels of immunoglobulin (Ig) G, IgM, IgA, CD3(+)CD4(+) T cells, CD3(+)CD8(+) T cells, B cells, natural killer (NK) cells, and C3 and C4 complement factors in peripheral blood in the next 24 hours after admission to the ICU. Patients with infection, sepsis, immunodeficiency, or concomitant immunosuppressive therapy were excluded. RESULTS: Levels of IgM, CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, and B lymphocytes correlated inversely with age. In turn, levels of CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, and C3 factor of the complement system correlated inversely with Acute Physiology and Chronic Health Evaluation II score. Multivariate Cox regression analysis censored at 28 days evidenced that levels of IgM played a protective role, whereas levels of NK cells behaved as a risk factor for mortality. Kaplan-Meier curves showed a cutoff of 58 mg/dL for IgM and 140 cells/mm(3) for NK cells. CONCLUSIONS: In conclusion, our results demonstrate that IgM plays a protective role in critically ill patients with no sepsis, whereas NK cell counts seem to play a deleterious one. Aging and severity at admission affect levels of key factors of the immune system in the blood of these patients.

Erythropoiesis-stimulating agents in anaemia due to chronic kidney disease: a cost-minimization analysis.

BACKGROUND: Some publications have shown that equivalent doses of erythropoiesis-stimulating agents (ESA) defined on label differ from those effective in clinical practice. Therefore, real costs could vary from theoretical costs in the treatment of anaemia in chronic kidney disease (CKD). OBJECTIVES: To perform a cost-minimization analysis to establish the economic impact of the principal ESAs used in treating anaemia secondary to CKD in daily practice. SECONDARY OBJECTIVES: to determine patient-month cost based on the erythropoietin resistance index (ERI); to analyze the difference in cost between pre-dialysis and peritoneal dialysis (PD) patients; and to analyze the association between iron deposits and ESA cost. SETTING: This study was carried out at 2 tertiary hospitals in Spain. METHOD: A multicentre cost-minimization analysis was performed in adult outpatients treated with ESAs for anaemia due to CKD. MAIN OUTCOME MEASURE: The primary outcome was the patient-month cost for each ESA. RESULTS: 409 patients were included. Median patient-month cost was: epoetin (103.2 [63.7, 187.8] euros), darbepoetin α (134.4 [67.2, 216.0] euros) and CERA (147.5 [98.3, 196.7] euros). Median patient-month cost according to ERI was: epoetin (1.60 [0.90, 2.60] euros/kg), darbepoetin α (2.01 [0.95, 3.48] euros/kg) and CERA (1.87 [1.33, 3.00] euros/kg). Median patient-month cost in pre-dialysis was 126.0 (73.7, 201.6) euros and in PD 153.0 (100.2, 275.4) euros. Median patient-month cost for patients with TSI < 20% was 147.5 (98.3, 224.9) euros compared to 100.9 (67.2, 196.7) euros which was the cost for patients with IST ≥ 20%. The median patient-month cost for patients with ferritin < 100 mcg/l was 134.4 (85.0, 201.6) euros compared to 100.8 (68.8, 196.7) euros, which was the cost for patients with ferritin ≥ 100 mcg/l (p = 0.242). CONCLUSION: Doses of CERA used in clinical practice are lower than those recommended on label, which directly influences cost and treatment efficiency. Cost stratification based on iron deposits has shown that patients with low TSI or ferritin require higher doses and consequently an associated higher cost. Thus, to guarantee adequate iron levels is essential in the rational use of ESAs.

Comparative uterine effects on ovariectomized rats after repeated treatment with different vaginal estrogen formulations.

OBJECTIVE: Topical estrogen therapy is recommended for the treatment of vaginal atrophy. This study was designed to compare the uterotrophic effects of a new estrogen vaginal formulation (0.005% estriol vaginal gel) and other existing topical treatments (Ovestinon(®) and Colpotrofin(®)). METHODS: Each one of the studied formulations was administered intravaginally to groups of ovariectomized rats with cytologically confirmed vaginal atrophy. The doses were adjusted by animal weight according to human dosage. After daily treatment for 14days, the animals were sacrificed and their vaginas and uteri removed. All uteri were weighted. Uteri and vaginas were fixed for histological evaluation. RESULTS: All three active formulations proved to be very effective in the cytological reversal of vaginal atrophy. However, they differ in their effects in the uteri. Ovestinon(®) and Colpotrofin(®) produced a significant increase in uterine weight, myometrial and endometrial thickness as well as histological modifications in the endometrium suggestive of estrogenic activity. Conversely, animals treated with 0.005% estriol vaginal gel, did not show significant weight increase or any other macroscopical or microcospical modifications of the uteri, an effect comparable to placebo. CONCLUSIONS: There are significant differences in the uterotrophic effect of three different topical estrogen formulations as tested in a rat model of vaginal postmenopausal atrophy. While the three formulations were equally effective in reversing vaginal atrophy, only the newly developed ultra-low dose 0.005% estriol vaginal gel has proved to lack any significant estrogenic effect on the uterus.

The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a new low-concentration estriol formulation (0.005% estriol vaginal gel), providing an ultra low dose of estriol per application (50 µg), for the local treatment of postmenopausal vaginal atrophy. METHODS: Postmenopausal women with symptoms and signs of vaginal atrophy were enrolled in a prospective, double-blind, placebo-controlled study. Women received either 1 g of vaginal gel containing 50 µg of estriol or placebo gel, daily for 3 weeks and then twice weekly up to 12 weeks. A cytological vaginal study, evaluation of vaginal pH, and assessment of symptoms and signs of vaginal atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. RESULTS: A total of 167 women were included (114 received estriol and 53 received placebo). After 12 weeks of therapy, a superiority of estriol compared with placebo gel was shown in the change in maturation value and vaginal pH (P < 0.001 and P < 0.001, respectively). The superiority of estriol was well demonstrated in improvement of vaginal dryness (P = 0.001) and the Global Symptom Score (P = 0.018). Estriol gel proved also superior in the improvement of several of the most outstanding vaginal signs of vaginal atrophy evaluated. After 3 weeks, estriol gel also showed a superiority over the placebo gel in most symptoms and signs evaluated. Treatment-related adverse events were similar among groups. CONCLUSIONS: 0.005% Estriol vaginal gel, a new formulation providing an ultra low dose of estriol per application, was shown to be safe and effective in the treatment of postmenopausal vaginal atrophy.

Toll-like receptor 2 deficiency delays pneumococcal phagocytosis and impairs oxidative killing by granulocytes.

Phagocytosis and killing of Streptococcus pneumoniae was compared in blood-derived wild-type (WT) and Toll-like receptor 2 (TLR2)-deficient (TLR2-/-) polymorphonuclear leukocytes (PMN). Phagocytosis of green fluorescent protein-transformed pneumococci was delayed in TLR2-/- PMN. These cells exhibited also a lower oxidative bactericidal activity against S. pneumoniae than WT PMN, suggesting that TLR2 modulates bacterial clearance in PMN.

Construction of the mobilizable plasmid pMV158GFP, a derivative of pMV158 that carries the gene encoding the green fluorescent protein.

Plasmid pMV158 has been employed to construct cloning non-mobilizable vectors for various Gram-positive organisms. Here we report the construction of a mobilizable pMV158-based plasmid that harbors the gene encoding the green fluorescent protein under the control of a promoter inducible by maltose. The plasmid was mobilized between strains of Streptococcus pneumoniae as well as from S. pneumoniae to Lactococcus lactis or Enterococcus faecalis at the same frequency as its parental. Transconjugant that received the GFP-tagged plasmid could be detected by their fluorescence, which was especially high in E. faecalis cells.