Monitoring the manufacturing and quality of medicines: a fundamental task of pharmacovigilance.

Unlabelled: The collection and assessment of individual case safety reports (ICSRs) is important to detect unknown adverse drug reactions particularly in the first decade after approval of new chemical entities. However, regulations require that these activities are routinely undertaken for all medicinal products, including older medicines such as generic medicinal products with a well-established safety profile. For the latter, the risk management plans no longer contain important risks, considered important safety concerns, on the basis that routine pharmacovigilance activity would not allow their further characterisation.

Evaluation of quantitative signal detection in EudraVigilance for orphan drugs: possible risk of false negatives.

Different strategies have been studied to allow a better characterization of the safety profile of orphan drugs soon after their approval. At the end of the development phases only few data are available because of the small number of subjects exposed to an orphan medicine for the treatment of rare or ultra-rare conditions. As a consequence, the evaluation of the safety profile is limited at the time of the first approval.

Pharmacovigilance of medicines for rare and ultrarare diseases.

The assessment of the safety of medicines for rare diseases during the development phase is often limited by the few data available from small numbers of patients. This also applies to a lesser extent during the postmarketing phase of the lifecycle of a medicine. By using all available sources of data for rare diseases drugs, and by carefully assessing these data, the most informed safety profile can be obtained.

Retina-derived POU domain factor 1 coordinates expression of genes relevant to renal and neuronal development.

Retina-derived POU domain Factor 1 (RPF-1), a member of POU transcription factor family, is encoded by POU6F2 gene, addressed by interstitial deletions at chromosome 7p14 in Wilms tumor (WT). Its expression has been detected in developing kidney and nervous system, suggesting an early role for this gene in regulating development of these organs. To investigate into its functions and determine its role in transcriptional regulation, we generated an inducible stable transfectant from HEK293 cells.

Web Health Monitoring Survey: A New Approach to Enhance the Effectiveness of Telemedicine Systems.

Background: Aging of the European population and interest in a healthy population in western countries have contributed to an increase in the number of health surveys, where the role of survey design, data collection, and data analysis methodology is clear and recognized by the whole scientific community. Survey methodology has had to couple with the challenges deriving from data collection through information and communications technology (ICT). Telemedicine systems have not used patients as a source of information, often limiting them to collecting only biometric data.

Is the digital divide an obstacle to e-health? An analysis of the situation in Europe and in Italy.

Introduction: The digital divide affecting elderly patients may compromise the diffusion of telemedicine systems for this age segment. It might be that the difficulties in the passage from trials to the effective distribution of telemedicine systems are also due to the awareness of a personal digital divide in the target population.

Materials And Methods: The analysis aims to estimate the number of people over the age of 50 years with potential cardiovascular problems able to access the Web.

The informative contribution of the "virtual medical visit" in a new heart failure telemedicine integrated system.

Introduction: Telemedicine systems consist of collection, transmission, and analysis of biometric data essentially based on instrumental measures. Our goal was to evaluate if information collected from patients has an incremental informative value in automatically rating the patient's health status.

Materials And Methods: We present preliminary results of a new telemedicine system (ASCOLTA) obtained by observation of 12 heart failure patients (New York Heart Association Class IIb-III).

Drug safety evaluation of defibrotide.

Introduction: Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions.

Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats.

Evidence from both animal and human studies suggests a role for dopamine in the therapeutic effect of antidepressant drugs. Consistently, dopamine receptor antagonists antagonize the effect of antidepressant drugs in different experimental models of depression. Neurosteroids, and in particular allopregnanolone, seem to be involved both in the pathophysiology of depression and in the mechanism of action of antidepressant drugs, and their role seems to be particularly important in the understanding of mood disturbances related to the different phases of the reproductive life in women.

Use of grape stalk, a waste of the viticulture industry, to obtain activated carbon.

Grape stalk is an organic waste produced in great amounts in the industrialization processes of grape. This work presents the results of studies carried out to use this waste as raw material to prepare activated carbon through the physical and chemical route. The physicochemical characterization of this material suggests the presence of unusually high levels of ashes.

A novel WT1 mutation in a 46,XY boy with congenital bilateral cryptorchidism, nystagmus and Wilms tumor.

The WT1 gene plays a crucial role in urogenital and gonadal development. Germline WT1 alterations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms tumor (WT), frequently occurring in combination. We report on a novel WT1 nonsense mutation (c.

Functional inactivation of the WTX gene is not a frequent event in Wilms' tumors.

For many years the precise genetic etiology of the majority of Wilms' tumors has remained unexplained. Recently, the WTX gene, mapped to chromosome Xq11.1, has been reported to be lost or mutated in approximately one-third of Wilms' tumors.

Cyclin D1 expression analysis in familial breast cancers may discriminate BRCAX from BRCA2-linked cases.

Most familial breast cancers arise in patients who tested negative for germline mutations in BRCA1 and BRCA2 genes (also referred to as BRCAX cases). Several studies aimed to define histopathological and molecular profiles characteristic of BRCA1, BRCA2 and BRCAX tumors have been performed. Major pathological and immunohistochemical differences have been reported in BRCA1 cancers compared to the other two groups, whereas less difference has been observed between BRCA2 and BRCAX cases.

Molecular evidence of the independent origin of multiple Wilms tumors in a case of WAGR syndrome.

Background: This study investigated the genetic events leading to tumorigenesis in a patient affected with WAGR syndrome who developed multiple distinct Wilms tumors (WTs).

Procedure And Results: At 1 year of age, the child developed two synchronous bilateral WTs that were resected by partial nephrectomy. Histologically, these tumors were fetal rhabdomyomatous nephroblastomas.

The murine Pou6f2 gene is temporally and spatially regulated during kidney embryogenesis and its human homolog is overexpressed in a subset of Wilms tumors.

We have previously suggested the transcription factor gene POU6F2 as a novel tumor suppressor involved in Wilms tumor (WT) predisposition. Since WT arises from pluripotent embryonic renal precursors, in this study we analyzed the expression of the murine homolog Pou6f2 during kidney embryogenesis and compared it to that of Wt1, the homolog of WT1, a known WT related gene involved in mesenchyme to epithelium conversion. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) performed for Pou6f2 on kidney specimens from embryos, pups, and adult mice, showed that the Pou6f2 mRNA was more abundant in the earliest analyzed phase of kidney organogenesis (E13) than in more advanced fetal stages and in adult animal.

The Italian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Italian language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease.

Carotid endarterectomy: a new technique replacing internal shunts.

Background: Carotid endarterectomy has been reported to increase the time free from cerebral ischemic events in both symptomatic and asymptomatic patients with a high grade of stenosis of the internal carotid artery. In cases in whom the compensatory circulation during the carotid clamp time is not sufficient, the use of intraluminal shunts has been proposed. However, the use of intraluminal shunts present several problems, such as the technical difficulties in positioning the shunt, the variability of time requested for the placement, the inconstancy of the blood flow during surgery, and the need to clamp off the carotid to introduce and remove the shunt.

Expression of KIF3C kinesin during neural development and in vitro neuronal differentiation.

KIF3A, KIF3B and KIF3C are kinesin-related motor subunits of the KIF3 family that associate to form the kinesin-II motor complex in which KIF3C and KIF3B are alternative partners of KIF3A. We have analysed the expression of Kif3 mRNAs during prenatal murine development. Kif3c transcripts are detectable from embryonic day 12.

Responsiveness of outcome measures in juvenile chronic arthritis. Italian Pediatric Rheumatology Study Group.

Objective: To examine the responsiveness of the disease activity measures more commonly used in juvenile chronic arthritis (JCA) clinical trials.

Methods: Data were obtained from an open-label, non-controlled, multicentre trial designed to investigate the efficacy of methotrexate (MTX) in children with JCA. Outcome measures, including physician and parent global assessments, functional ability measures, articular variables, and laboratory indicators of systemic inflammation, were assessed at baseline and after 6 months of MTX treatment in 132 patients.

A computer-driven approach to PCR-based differential screening, alternative to differential display.

Motivation: Polymerase chain reaction (PCR)-based RNA fingerprinting is a powerful tool for the isolation of differentially expressed genes in studies of neoplasia, differentiation or development. Arbitrarily primed RNA fingerprinting is capable of targeting coding regions of genes, as opposed to differential display techniques, which target 3' non-coding cDNA. In order to be of general use and to permit a systematic survey of differential gene expression, RNA fingerprinting has to be standardized and a number of highly efficient and selective arbitrary primers must be identified.

Changes in gene expression during the growth arrest of HepG2 hepatoma cells induced by reducing agents or TGFbeta1.

The growth of hepatoma cells can be inhibited by treatment with TGFbeta1 or with exogenous reducing agents. To gain information on the molecular mechanisms underlying growth arrest, we visualized and compared gene expression profiles of proliferating versus non proliferating HepG2 cells by computer-assisted gene fishing, an improved technique of RNA fingerprinting that allows the selective amplification of coding regions within transcripts. While many transcripts are selectively regulated by either treatment, a set of bands appear to be coordinately regulated by 2ME and TGFbeta1, suggesting their possible involvement in the mechanisms of growth arrest.

Performance of the preliminary definition of improvement in juvenile chronic arthritis patients treated with methotrexate. Italian Pediatric Rheumatology Study Group.

Objective: To investigate the performance of the core set of outcome measures and the preliminary definition of improvement (PDI) in the assessment of response to methotrexate (MTX) treatment in children with juvenile chronic arthritis (JCA).

Methods: Data were obtained from an open label, non-controlled trial designed to investigate the efficacy of MTX in children with JCA. All patients had the core set of variables assessed at baseline and after six months of treatment.

Oral versus intramuscular methotrexate in juvenile chronic arthritis. Italian Pediatric Rheumatology Study Group.

Objective: To compare the efficacy and safety of methotrexate (MTX) after oral and intramuscular administration in children with juvenile chronic arthritis (JCA).

Methods: Pediatric rheumatology centers in Italy participated in this short-term, prospective, open trial. Each investigator was allowed to choose the oral or intramuscular route of administration according to his personal preference in everyday clinical practice.

KIF3C, a novel member of the kinesin superfamily: sequence, expression, and mapping to human chromosome 2 at 2p23.

Kinesins are microtubule-dependent molecular motors involved in intracellular transport and mitosis. Here, we report the cloning, sequencing, mapping, and expression of a novel member of the kinesin superfamily. The sequence of this newly identified human cDNA reveals an open reading frame encoding a putative protein of 792 residues.