Individualized Treatment of Genotype 1 Na?ve Patients: An Italian Multicenter Field Practice Experience

Background

Triple therapy including Telaprevir or Boceprevir still represents in many European countries the standard of care for patients with Hepatitis C Virus genotype 1 infection. The number of patients who received this treatment resulted generally lower than expected. We investigated, among naïve patients, number and characteristics of treatment candidates who were started on triple or dual therapy in comparison to those who were deferred.

Patients and Methods

621 naïve treatment candidates were prospectively evaluated at each center. Factors associated with decision to defer or treat with dual or triple therapy were investigated by univariate and multivariate analyses. Rates of Sustained Virological Response and safety profile were analysed.

Results

Of candidates to treatment, 33% did not received it. It was mostly due to high risk of Interferon-induced decompensation. Of 397 patients who were started on treatment, 266 (67%) received triple, 131 dual. Among patient receiving treatment, unfavorable IL28B, severe liver damage and higher albumin were independently associated with the physician decision to administer triple therapy. Sustained Virological Response after dual therapy was 66.4%, after triple 73.7% (p = 0.14). 142 patients received Telaprevir. The choice of Telaprevir-based therapy was associated with higher Body Mass Index and advanced liver disease. Sustained Virological Response rates were 71.1% after Telaprevir and 76.6% after Boceprevir.

Conclusions

Individualizing treatment with available regimens allows to maximize Sustained Virological Response and to reduce the number of patients who remain untreated. High proportion of patients with severe liver damage urgently need Interferon free treatment.     

Speciation study of the anti-inflammatory drug tenoxicam (Htenox) with Cu(II): X-ray crystal structure of [Cu(tenox)(2)(py)(2)].EtOH

A speciation study was carried out in aqueous solution of the anti-inflammatory drug tenoxicam (Htenox), under quasi-physiological conditions (temperature of 37 degrees C and ionic strength 0.15 M NaCl) in order to determine the acidity constants from spectrophotometric studies, the pK(a) values found being pK(1)=1.143+/-0.008 and pK(2)=4.970+/-0.004. Subsequently, the spectrophotometrical speciation of the different complexes of Cu(II) with the drug was performed under the same conditions of temperature and ionic strength, observing the formation of Cu(Htenox)(2)(2+) with log beta(212)=20.05+/-0.01, Cu(tenox)(2) with log beta(012)=13.6+/-0.1, Cu(Htenox)(2+) with log beta(111)=10.52+/-0.08, as well as Cu(tenox)(+) with log beta(011)=7.0+/-0.2, all of them in solution, and solid species Cu(tenox)(2)(s) with an estimated value of log beta(012)(s) approximately 18.7. The crystalline structure of the complex [Cu(tenox)(2)(py)(2)]. EtOH, was also determined, and it was observed that tenoxicam employs the oxygen of the amide group and the pyridyl nitrogen to bond to the cation.     

Weather daily variation in winter and its effect on behavior and affective states in day-care children

This study aimed to analyze the impact of winter weather conditions on young children’s behavior and affective states by examining a group of 61 children attending day-care centers in Florence (Italy). Participants were 33 males, 28 females and their 11 teachers. The mean age of the children at the beginning of the observation period was 24.1 months. The day-care teachers observed the children’s behavioral and emotional states during the morning before their sleeping time and filled in a questionnaire for each baby five times over a winter period of 3 weeks. Air temperature, relative humidity, air pressure and solar radiation data were collected every 15 min from a weather station located in the city center of Florence. At the same time, air temperature and relative humidity data were collected in the classroom and in the garden of each day-care center. We used multilevel linear models to evaluate the extent to which children’s emotional and behavioral states could be predicted by weather conditions, controlling for child characteristics (gender and age). The data showed that relative humidity and solar radiation were the main predictors of the children’s emotional and behavioral states. The outdoor humidity had a significant positive effect on frustration, sadness and aggression; solar radiation had a significant negative effect only on sadness, suggesting that a sunny winter day makes children more cheerful. The results are discussed in term of implications for parents and teachers to improve children’s ecological environment.     

Different epithelia in the distal human male urethra

Summary The distal segment of the human male urethra, in particular the fossa navicularis, was studied with light- and electron microscopy as well as by means of histochemical and immunocytochemical methods. The fossa navicularis of the urethra contains a circumscribed zone of extremely thick, non-keratinized stratified squamous epithelium composed of cells containing a large amount of glycogen. These cells lack acid phosphatase activity and lysozyme-like immunoreactivity, both of which can be demonstrated to varying extents in the other zones of the distal male urethra. These glycogen-rich cells are considered to be the substrate for an endogenous flora of lactobacteria, whereas the acid-phosphatase activity and the lysozyme-like immunoreactivity indicate the presence of macrophages and the secretion of bactericidal agents at the epithelial surface. These observations suggest that the different zones with heterogeneous properties in the distal male urethra probably represent a defense system against the invasion of pathogenic microorganisms. Moreover, the glycogen-rich zone, which resembles the glycogen-rich epithelium of the vagina, is estrogen-dependent. This is demonstrated in cases of sex reversal in which after long-lasting estrogen treatment the glycogen-rich zone becomes extremely extended by displacement of the neighbouring epithelium.     

Histomorphology of an ileal orthotopic neobladder: 24 Year's follow-up

No morphological data are so far available about long-term (over 15 years) adaptation and outcome of ileal neobladders. In this single case report we have studied a 72-year-old man who underwent reconstruction of an ileal neobladder 24 years ago. The ileal epithelium shows changes toward a colonic aspect with villous atrophy and increased goblet cell number although, as in normal ileum, sialomucins are the most abundant secretory products. Neuroendocrine cells are reduced to a few elements of a single morphological class. Even in the presence of a low apoptotic rate reduced cell proliferation causes mucosal thinning. These adaptive mechanisms grant an excellent clinical and functional result even beyond 20 years after surgery. It is suggested that ileal neobladder can constitute an important model for the study of epithelial differentiation control.     

Regulation of ABA levels in senescing petals of rose flowers

During the vase life of a rose flower, changes in the levels of abscisic acid (ABA) were observed: a decrease during the first 3 days, followed by a steady state at a low level, and finally a sharp increase in late senescence. Feeding [2-¹⁴C]ABA to isolated petals showed that metabolism was very active despite the age of the flower, oxidation processes increased with age, whereas conjugation decreased but the level of nonmetabolized ABA remained stable. When the isolated petal was subjected to water stress, whatever its age, the ABA level increased. Hydrolysis of ABA-GE was not involved in this phenomenon. Thus, ABA synthesis occurred in the isolated petal; it could be directly correlated to the decrease in water potential. However, the ABA increase in isolated petals was limited. Moreover, on the rose tree, increases in ABA levels were not correlated to water potential changes. ABA levels seemed, therefore, mainly regulated by changes in import from leaves and other parts of the flower.     

Distribution and fine structure of the lymphatic system in the human testis

Summary The distribution of lymph vessels in the human testis was investigated using ink injection methods, and light and electron microscopy. Lymph capillaries occur in the septula testis but are absent in the intertubular tissue. They consist of endothelial cells provided with an incomplete basal lamina and anchoring filaments of the adjacent connective tissue. Frequently, the endothelial cells are separated by gaps measuring up to 2m. The lymph capillaries of the septula testis are connected to lymph vessels in the rete testis and tunica albuginea. These vessels have occasional smooth muscle cells and valves. At the posterior margin of the testis, the network of lymph vessels merges into collecting ducts, which together with vessels derived from the rete testis are drained by the lymphatic system in the spermatic cord.Dedicated to Prof. Henriette Oboussier, Hamburg, on the occasion of her 65th birthday     

Sexual Dimorphism in Tuberculosis Incidence: Children Cases Compared to Adult Cases in Tuscany from 1997 to 2011

Background

In most countries, men seem to be more susceptible to tuberculosis (TB) than women, but only few studies have investigated the reasons of this gender incidence difference. The effect of sexual hormones on immunity is possible.

Methods

Data from children and adults, living in Tuscany, hospitalized for TB in all the thirty-one regional hospitals from January 1^st 1997 to December 31^st 2011, were analyzed using the International Classification of Disease, 9^th Revision, Clinical Modification.

Results

During the study period, 10,744 patients were hospitalized with TB diagnosis, precisely 279 (2.6%) children [0–14 years], 205 (1.9%) adolescents [15–18 years] and 10,260 (95.5%) adults [≥18 years]. The male population ranged from 249 patients (51.4%) in children and adolescents, to 6,253 (60.9%) in adults. Pulmonary TB was the most common form both in children and adults. Men were more likely than women to have pulmonary TB after puberty, while no significant differences were found between males and females in the hospitalized children. The male gender also resulted the most affected for the extra-pulmonary disease sites, excluding the lymphatic system, during the reproductive age.

Conclusions

Our findings suggest a possible role of sexual hormones in the development of TB. No significant male-female difference was found in TB incidence among children, while a sex ratio significantly different from 1∶1 emerged among reproductive age classes. An increased incidence difference also persisted in older men, suggesting that male-biased risk factors could influence TB progression. Some limitations of the study are the sample size, the method of discharge diagnosis which could be deficient in accuracy in some cases, the increasing number of immigrants and the lack of possible individual risk factors (smoke and alcohol). Further studies are needed to investigate the possible hormone-driven immune mechanisms determining the sexual dimorphism in TB.