Adherence to hormone therapy in patients with mCRPC: psychometric validation of the A-HT questionnaire.

Abstract: The incidence rate of prostate cancer (PCa) in many Western countries is high, contributing greatly to the cancer disease bur-den. In most cases, patients progress to metastatic disease defined as castration-resistant prostate cancer after androgen deprivation (mCRPC) following primary treatment where the majority of patients receive first-line new-generation oral hormonal therapies (HT) such as Abiraterone Acetate (AA) and Enzalutamide (ENZ). Despite the importance of correct intake of these drugs, adherence in patients with mCRPC is still poorly investigated and managed with measures not specific to this population. A self-report questionnaire was developed and validated with women with breast cancer treated with oral HT (A-BET). Therefore, this study aims to test the psychometric properties of this instrument on patients with mCRPC treated with AA or ENZ. A prospective observational validation study. The questionnaire was completed by all participants and again after 7/10 days by a randomized subsample to assess stability. Sixty-six patients completed the study (mean age of 72.8 years) and 31 completed the re-test (mean age of 72.7 years). Content validity reported excellent results. Cronbach's alpha of each item showed a strong correlation. Validation of an instrument to measure adherence to HT in patients with mCRPC can be a valuable tool for health professionals involved in patient care. In addition, having a population-specific validated instrument allows to make comparisons between results from different observations.

The interaction between Environmental Enrichment and fluoxetine in inhibiting sucrose-seeking renewal in mice depend on social living condition.

RATIONALE: Several single or combined therapeutic approaches have been developed to treat addiction, however with partial efficacy in preventing relapse. Recently, the living environment has been suggested as a critical intervening factor determining the treatment outcomes. Despite accumulating evidence confirming a role of living conditions in the vulnerability to addictive behaviours, their impact on single or integrative therapeutic strategies preventing relapse is yet to be identified. OBJECTIVES: Here, we explore the possible interaction between brief Environmental Enrichment (EE) exposure and acute fluoxetine administration in inhibiting sucrose-seeking behaviours, and whether this effect could be affected by living environment. METHODS: Social and isolated adult male C57BL/6 mice were trained to sucrose self-administration associated to a specific conditioning context (CxA), followed by a 7-day extinction in a different context (CxB). Afterwards, mice were exposed for 22 h to EE and then injected with fluoxetine (10 mg/kg, i.p.) 1 h before a CxA-induced sucrose-seeking test. RESULTS: Brief EE exposure and acute fluoxetine administration alone inhibited context-induced sucrose-seeking in both housing conditions; however, they exhibited additive properties only in social condition. CONCLUSIONS: Our data show that social environment may influence the EE/fluoxetine interaction in inhibiting relapse to sucrose. These findings suggest that setting up proper living conditions to boost the efficacy of therapeutic approaches may represent a fundamental strategy to treat addiction disorders.

Valorization of agro-industrial wastes to produce hydrolytic enzymes by fungal solid-state fermentation.

Nowadays, significant amounts of agro-industrial wastes are discarded by industries; however, they represent interesting raw materials for the production of high-added value products. In this regard, orange peels (ORA) and exhausted sugar beet cossettes (ESBC) have turned out to be promising raw materials for hydrolytic enzymes production by solid state fermentation (SSF) and also a source of sugars which could be fermented to different high-added value products. The maximum activities of xylanase and exo-polygalacturonase (exo-PG) measured in the enzymatic extracts obtained after the SSF of ORA were 31,000 U·kg-1 and 17,600 U·kg-1, respectively; while for ESBC the maximum values reached were 35,000 U·kg-1 and 28,000 U·kg-1, respectively. The enzymatic extracts obtained in the SSF experiments were also employed for the hydrolysis of ORA and ESBC. Furthermore, it was found that extracts obtained from SSF of ORA, supplemented with commercial cellulase, were more efficient for the hydrolysis of ORA and ESBC than a commercial enzyme cocktail typically used for this purpose. In this case, maximum reducing sugars concentrations of 57 and 47 g·L-1 were measured after the enzymatic hydrolysis of ESBC and ORA, respectively.

The rs2108622 polymorphism is related to the early risk of ischemic stroke in non-valvular atrial fibrillation subjects under oral anticoagulation.

Oral anticoagulant treatments, such as vitamin K antagonists (VKAs), are the main treatments administered to atrial fibrillation (AF) patients in order to prevent ischemic stroke (IS). However, the genes involved in the VKA metabolism can undergo variations in a single nucleotide (SNP). These SNPs may then affect the VKA target enzyme (VKORC1), VKA degradation enzyme (CYP2C9), and vitamin K bioavailability enzyme (CYP4F2). We genotyped these SNPs in a cohort of patients with non-valvular AF who were under VKA treatment after suffering an IS. Clinical variables, CHADS2-VASC score and data about the international normalized ratio (INR) within the therapeutic range were all recorded. DNA was extracted from blood and genotyping was carried out by DNA sequencing. The main endpoint was the time from VKA onset to IS. Of a total of 356 consecutive IS patients monitored, 33 were included in the study. The median time to the event was 2248.0 days (interquartile range [IQR] 896.3-3545.3). The median CHADS2-VASC score was 4.0 (IQR 3.0-6.0). When we considered the risk of IS within 2 years under VKA treatment, we found that only the rs2108622 AA genotype was significantly associated with this endpoint (early IS) (hazard ratio 6.81, 95% CI 1.37-33.92, p = 0.019). Kaplan-Meier curve analysis also showed a significant relationship between early IS and rs2108622 AA genotype (Log rank p = 0.022). The CYP4F2 gene rs2108622 polymorphism was associated with a risk of early IS in NV-AF patients under VKA treatment.

Valorization of exhausted sugar beet cossettes by successive hydrolysis and two fermentations for the production of bio-products.

Exhausted sugar beet cossettes (ESBC) show an enormous potential as a source of sugars for the production of bio-products. Enzyme hydrolysis with the combined effect of mainly cellulases, xylanases and pectinases, turned out to be very efficient, obtaining almost double the concentration of sugars measured with the sole action of Celluclast® and ß-glucosidase, and increasing 5 times the hydrolysis rate. As the sole pretreatment, ESBC soaked in the hydrolysis buffer were autoclaved, avoiding the application of severe conventional biomass pretreatments. Moreover, a promising alternative for the complete utilization of glucose, xylose, arabinose, mannose and maltose contained in ESBC is proposed in this paper. It consists of sequential fermentation of sugars released in the hydrolysis step to produce bioethanol and lactic acid as main bio-products. Compared to separate fermentations, with this strategy glucose and hemicellulose derived sugars were completely consumed and the 44% of pectin derived sugars.

Comparison of intra-operative analgesia provided by intravenous regional anesthesia or brachial plexus block for pancarpal arthrodesis in dogs.

The aim of this study was to compare intravenous regional anesthesia (IVRA) and brachial plexus block (BPB) for intra-operative analgesia in dogs undergoing pancarpal arthrodesis (PA). Twenty dogs scheduled for PA were intramuscularly sedated with acepromazine (0.03 mg/kg), general anesthesia was intravenously (IV) induced with thiopental (10 mg/kg) and, after intubation, maintained with isoflurane in oxygen. In 10 dogs (GIVRA) IVRA was performed on the injured limb administering 0.6 ml/kg of 0.5% lidocaine. In 10 dogs (GBPB) the BPB was performed at the axillary level with the help of a nerve stimulator and 0.3 ml/kg of a 1:1 solution of 2% lidocaine and 1% ropivacaine was injected. During surgery fentanyl (0.002 mg/kg IV) was administered if there was a 15% increase of HR and/or MAP compared to the values before surgical stimulation. All the standard cardiovascular and respiratory parameters were continuously monitored during surgery. The duration of surgery and the time of extubation were recorded. Data were compared with a 1-way ANOVA test (P<0.05). No patients required fentanyl administration during surgery. All the recorded parameters were similar in the two groups. The two techniques were similar in providing intra-operative analgesia in dogs undergoing orthopaedic surgery.

Alveolar recruiting maneuver in dogs under general anesthesia: effects on alveolar ventilation, gas exchange, and respiratory mechanics.

The aim of this study was to evaluate the effects of a recruiting maneuver (RM) on lung aeration, gas exchange, and respiratory mechanics during general anesthesia in mechanically ventilated dogs. A thoracic computed tomography (CT) scan, an arterial blood sample, and measurement of respiratory mechanics were performed 10 min before (baseline) and both 5 and 30 min after a vital capacity RM in 10 dogs under general anesthesia. The RM was performed by inflating the lung at 40 cm H(2)O for 20 s. Lung aeration was estimated by analyzing the radiographic attenuation of the CT images. Lung aeration and gas exchange improved significantly 5 min after the RM compared to baseline and returned to values similar to baseline by 30 min. Static lung compliance was not significantly affected by the RM. An RM induces a temporary improvement in lung function in healthy dogs under general anesthesia.

First Mass-resolved Measurement of High-Energy Cosmic-Ray Antiprotons.

We report new results for the cosmic-ray antiproton-to-proton ratio from 3 to 50 GeV at the top of the atmosphere. These results represent the first measurements, on an event-by-event basis, of mass-resolved antiprotons above 18 GeV. The results were obtained with the NMSU-WIZARD/CAPRICE98 balloon-borne magnet spectrometer equipped with a gas-RICH (Ring-Imaging Cerenkov) counter and a silicon-tungsten imaging calorimeter. The RICH detector was the first ever flown that is capable of identifying charge-one particles at energies above 5 GeV. The spectrometer was flown on 1998 May 28-29 from Fort Sumner, New Mexico. The measured p&d1;/p ratio is in agreement with a pure secondary interstellar production.

[Correlation between functional and radiographic data, and broncho-alveolar cytology in patients with diffuse interstitial lung disease]. / Correlazioni fra dati funzionali, radiografici e cellularità bronchiolo-alveolare in pazienti affetti da pneumopatie interstiziali diffuse.

BACKGROUND: "Interstitial Lung Disease" is a term that includes a heterogeneous group of disorders characterized by variable degrees of parenchymal inflammation (alveolitis) and fibrosis. Alveolitis represents one of the most important aspects of ILD and its characterization by broncho-alveolar lavage (BAL) can give explanations of the different clinical features, in association with the evaluation of physiological changes and High Resolution Computed Tomography (HRCT). The aim of this study was to establish a correlation between variations in broncho-alveolar cells and anatomical-functional alterations in patients affected by ILD before and after corticoid therapy. METHODS: Thirty-one patients (14 males 17 females) were introduced in the study and were evaluated for clinical signs, functional parameters, HRCT and cyto-immunological aspects of BAL fluid. All data were acquired at the admission in the study, after 60 and 180 days. Patients had received prednisone 1 mg/kg/die for 60 days and, then, 0.25 mg/kg/die for 120 days. RESULTS: In lymphocyte alveolitis, a clinical-radiological improvement was frequently observed after therapy while in those with neutrophilic and eosinophilic components, no improvement was detected. CONCLUSIONS: In conclusion, BAL represents a useful tool in qualifying ILD which can be easily monitored by clinical, functional and radiological data. Therefore, a new method for the diagnosis and monitoring of ILD is suggested. This method has the marked advantage to reach a reliable diagnosis even in a high percentage of patients who refuse or can not undergo the biopsy assay.

Prevalence of phenotypic activated protein C resistance (APCR) in venous thromboembolic patients.

Until the discovery of activated protein C resistance (APCR), less than 10% of patients with venous thromboembolism (VT) showed defects in proteins involved in the inhibition of coagulation. APCR is caused by a single point mutation in the factor V gene, and it is accepted that APCR is associated with an increased risk for VT. In this work, we studied the prevalence of APCR in venous thromboembolic patients and found it to be 10.5% compared with 4.5% in controls (p = 0.105).

Curdlan sulfate (CRDS) in a 21-day intravenous tolerance study in human immunodeficiency virus (HIV) and cytomegalovirus (CMV) infected patients: indication of anti-CMV activity with low toxicity.

This study evaluated tolerance (and possible efficacy) for 21 days of i.v. administration at three dose levels of curdlan sulfate (CRDS) (a semisynthetic sulfated polysaccharide), administered over 30 minutes, in HIV and CMV (in some cases) infected individuals with CD4 levels < 500 cells/mm3. Half of the subjects were previously treated with reverse transcriptase inhibitors (RTI) (which were continued during the CRDS administration) and half the patients had no prior RTI treatment. Evaluation of other sulfated polysaccharides in HIV had been discontinued due to side effects and lack of activity. Three groups of HIV patients (also including subsets with CMV infection) were treated separately with 50 mg/70 Kg, 100 mg/70 Kg and 200 mg/70 Kg of CRDS infused i.v. over thirty minutes daily for 21 days. In each dose group, half of the patients selected were being treated with a RTI and half were on no RTI. Patients were monitored for CD4 cell levels, viral load in some cases, and safety parameters in blood. Samples of urine and semen were additionally taken for CMV by culture and for PCR assay in subsets of participants. CRDS in this 21 day study was well-tolerated and produced few reportable side effects. Systematic decreases in platelets and increases in p24 antigen previously seen with dextran sulfate were not observed in this study with CRDS. In the 21 patients testing positive for CMV at the start of the study, 12 were CMV negative at the end of 21 days. In an untreated historical control group, 0/36 went from CMV positive to negative over a period of 13-15 years. The anti-CMV activity of CRDS in this study, therefore, had a p value < 0.001, based on these historical controls. The marked temporary increases in CD4 levels seen in the single dose and the seven-day CRDS studies on HIV patients were also seen for 21 days in the current study (p = 0.0001). Treatment with CRDS seems promising against CMV in HIV infected patients, even with once daily dosing of this two-hour half-life drug. CRDS was well tolerated and its lack of toxicity makes it an attractive candidate for CMV-infected HIV patients. Multiple daily dosing, or the continuous infusion of CRDS, could lead to increased effectiveness against both HIV and CMV, especially in combination with other agents. Given the toxicity of existing anti-CMV agents, and considering the emerging importance of CMV in atherosclerotic disease, further studies on CRDS are warranted.

Value of the determination of TNF-alpha in the plasma of patients with non-Hodgkins lymphoma.

The present report describes the value of the plasma determination of TNF-alpha, at diagnosis, in 43 patients with non-Hodgkin's lymphoma (NHL), related to their clinical presentation and the new International Prognosis Index (IPI). We also compare the levels of TNF-alpha with those of LDH, beta-2-microglobulin (beta-2-m), and ferritin. At diagnosis, the mean values of the quotients between the marker values and the maximum value of normal (ratio:r-) are placed 7 times higher than normal for r-TNF-alpha, whereas those of r-beta-2-m and r-LDH are 2,4 and 1,4 times more respectively. We found a relationship between the value of r-TNF-alpha and the ECOG, Ann Arbor stage, the number of affected extranodal sites, and between the values of r-beta-2-m with r-LDH. The best correlation was obtained between the values of r-TNF-alpha and r-beta-2-m and IPI, however r-TNF-alpha best stratify the four risk groups in this prognosis index.

Immunohistochemical localization of filaggrin in benign, premalignant and malignant cervical tissue.

Epithelial distribution of filaggrin, a histidine-rich protein related to squamous terminal differentiation, was investigated in 87 cervical biopsies using an avidin-biotin-peroxidase technique with a monoclonal anti-human filaggrin antibody (AKH1). Normal squamous cervical epithelium exhibited a positive homogeneous immunoperoxidase stain in the upper parabasal, intermediate and superficial cell layers. Similar findings were obtained in cervical condylomas, although full-thickness staining was observed in 35.7% of the cases (P < 0.001). Filaggrin expression in CIN was inversely related to the severity of the lesion (P < 0.001). An irregular staining pattern was present in most high-grade CIN. Filaggrin expression was closely connected to the degree of tumour differentiation (P < 0.05) in squamous cell carcinomas of the cervix. Abnormal filaggrin stainings identified a premalignant/malignant cervical squamous lesion with a positive predictive value of 92.3%. Non-squamous epithelia showed lack of filaggrin expression. Filaggrin may therefore be considered a marker of squamous differentiation in both the normal and pathological human uterine cervix.

Protective effects of nedocromil sodium on cellular and biohumoral components present in the bronchial alveolar lavage fluid and in peripheral blood in atopic asthmatics.

Nedocromil sodium, a disodium salt of a pyroquinolinedicarboxylic acid, raises the bronchial hyperresponsiveness threshold, because it inhibits the mediators released by the various cells, and reduces the involvement and activation of inflammatory cells. The aim of this study was to evaluate the state of activation of the immunocompetent cells and the main chemical mediators present in the bronchoalveolar lavage (BAL) fluid from 10 atopic asthmatic patients, before and after treatment with nedocromil sodium. The following examinations were performed before treatment and after 120 days of therapy with nedocromil sodium at 16 mg/day (two 2-mg puffs x 4): the level of chemical mediators and the state of activation of immunocompetent cells in BAL fluid; immunological analytes in activation of immunocompetent cells in BAL fluid; immunological analytes in peripheral blood; aspecific bronchial challenge test with ultrasonicated bidistilled H2O fog to evaluate variations in the hyperreactivity threshold; questionnaire to determine any adverse effects of treatment (cough, breathlessness, sleep disorders). Our findings demonstrate that nedocromil sodium prevents the release of chemotactic and inflammatory mediators by the effector cells and thus stabilizes microvascular permeability and epithelial damage, so raising the threshold of response to bronchoconstriction stimuli. Lastly, nedocromil sodium is associated with a better preventive therapeutic efficacy and good tolerance and can therefore be suggested as a valid drug to be used in the long-term treatment of bronchial asthma.

[Multiple carcinomas: considerations on several cases with synchronous/metachronous involvement of the respiratory tract]. / Carcinomi multipli: considerazioni su alcuni casi a coinvolgimento sincrono e/o metacrono delle vie respiratorie.

The authors report their observations on 7 cases of multiple malignant tumors during the period 1988/1992 (frequency of 0.03 x 100). They report that primary malignant tumors involved the laryinx and the wang, and both the lungs in a synchronous or metacronous way. They suggest that pathogenesis of multiple malignant tumors may be very similar to that of multiple endocrinous neoplasms.

Interposition of the first jejunal loop for reconstruction after total gastrectomy.

A new technique of reconstruction after total gastrectomy by interposing the first jejunal loop between the esophagus and the duodenum, is described. Vascular and neural integrity of the interposed intestinal segment is "guaranteed", resulting in acceptable muscular activity on intestinal contents and partial digestive function, with limited post-operative complications. The interposed jejunal loop assumes reservoir function and permits almost normal eating habits. Application of this technique to 18 patients undergoing total gastrectomy has resulted in a more than satisfactory post-operative functional and nutritional status over a one to 14 year follow-up period.

Expression of estrogen receptors, progesterone receptors, and an estrogen receptor-associated protein in the human cervix during the menstrual cycle and menopause.

Estrogen receptors (ERs), progesterone receptors (PRs), and P29, an ER-associated protein, were studied immunohistochemically in human cervix with use of specific monoclonal antibodies. In ectocervical epithelium, homogeneous staining was found for P29 throughout the menstrual cycle and after menopause. Weak or moderate staining was found for ER in the basal and, occasionally, the parabasal layers of ectocervix during the proliferative phase. In contrast, staining decreased in secretory phase and postmenopausal epithelia. Staining was negative for PR in all the exocervical epithelia. Heterogeneous staining, more pronounced for P29, was found for the three antigens of the study in endocervical epithelium. Staining did not change with the hormonal status of patients, except for ER, where staining decreased during the secretory phase. Stromal cells were negative or weakly positive, whereas muscular fibers were positive. This study suggests that the capacity of response of the steroid apparatus of cervical cells to fluctuations of circulating estrogens and progestins is limited compared with some of the cell functions, such as mucus secretion, or with other target tissues, such as endometrium. Additionally, the differences found in the pattern of expression of the three antigens studied suggest that the steroid-dependent growth and differentiation in ectocervix is regulated differently to endocervix.