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Adsorption studies (kinetic, batch and dynamic assays) were carried out for lead removal from aqueous solutions using wastes from the wine industry. The adsorbents used were obtained from grape stalk and pomace#. These materials were carbonized, briquetted and activated with steam. Addition of a leaching step before activation lowered the high ash content of the materials. The products were characterized by elemental and proximate analysis, point of zero charge pH, specific surface area, pore-size distribution, Fourier transform infrared spectroscopy and surface acidic and basic groups. Considering the physicochemical and textural properties of the adsorbents, a comparative analysis of the results was made. These solids showed a marked basic character; therefore, the pH was a very important variable in adsorption tests, and thus it was necessary to maintain the pH in a favourable range. Batch equilibrium assays showed that the tested adsorbents had good adsorption capacities, better than the ones reported previously for similar materials. In dynamic tests, the removal of lead by both activated carbon briquettes was good and attributed to the coupling of adsorption and precipitation as a result of the increase in the pH values, which could not be controlled. [ABSTRACT FROM AUTHOR]

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. Society assumes that unexpected adverse reactions causally related to pharmacological activity are very unlikely to be detected for such well-established medicines, but important risks can still occur. For these products, a change in the safety profile which is brand or source specific and usually local in nature, associated with failures with the adequate control of quality of manufacturing or distribution are important safety issues. These may be the consequence of manufacturing and pharmacovigilance quality systems that are not fully integrated over the product life cycle (e.g. inadequate control of quality defects affecting one or multiple batches; inadequate impact assessment of change/variation of manufacturing, quality control testing, storage and distribution processes; inadequate control over the distribution channels including the introduction of counterfeit or falsified products into the supply chain). Drug safety hazards caused by the above-mentioned issues have been identified with different products and formulations, from small molecules to complex molecules such as biological products extracted from animal sources, biosimilars and advanced therapy medicinal products. The various phases of the drug manufacturing and distribution of pharmaceutical products require inputs from pharmacovigilance to assess any effects of quality-related issues and to identify proportionate risk minimisation measures that often have design implications for a medicine which requires a close link between proactive vigilance and good manufacturing practice. To illustrate our argument for closer organisational integration, some examples of drug safety hazards originating from quality, manufacturing and distribution issues are discussed., Plain Language Summary: Monitoring the manufacturing and quality of medicines: the fundamental task of pharmacovigilance Pharmacovigilance is the science relating to the collection, detection, assessment, monitoring, and prevention of adverse reactions with pharmaceutical products. The collection and assessment of adverse reactions are particularly important in the first decade after marketing authorisation of a drug as the information gathered in this period could help, for example, to identify complications from its use which were unknown before its commercialization. However, when it comes to medicines that have been on the market for a long time there is general acceptance that their safety profile is already well-established and unknown adverse reactions unlikely to occur. Nevertheless, even older medicines, such as generic drugs, can generate new risks. For these drugs a change in the safety profile could be the result of inadequate control of their quality, manufacturing and distribution systems. To overcome such an obstacle, it is necessary to fully integrate manufacturing and pharmacovigilance quality systems in the medicine life-cycle. This could help detect safety hazards and prevent the development of new complications which may arise due to the poor quality of a drug. Pharmacovigilance activities should indeed be included in all phases of the drugs' manufacturing and distribution process, regardless of their chemical complexity to detect quality-related matters in good time and reduce the risk of safety concerns to a minimum., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: The Editor-in-Chief of Therapeutic Advances in Drug Safety is an author of this paper; therefore, the peer-review process was managed by alternative members of the Board and the submitting Editor had no involvement in the decision-making process., (© The Author(s), 2021.)

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. In the post-marketing period, all available sources should be combined for a better understanding of the safety of orphan drugs. These sources, include outputs from large databases such as the European Medicines Agency's EudraVigilance database. Analyses of data from this source are required to be performed by marketing authorization holders (MAHs) as part of their signal management activities. In 2018, the Pharmacovigilance Risk Assessment Committee (PRAC) assessed 114 confirmed signals, 79% of which included data from EudraVigilance. MAHs have access to statistical calculations for drug-event combinations (DECs) from EudraVigilance, provided in the form of measures of disproportionality of ratios of the observed proportion of spontaneous cases for a DEC in relation to the proportion of cases that would be expected if no association existed between the drug and the event. However, such statistical summaries for orphan drugs could be misleading because of the very limited safety data available for orphan drugs (under-reporting together with low numbers of exposed patients). In addition, the applied statistical methodology in most instances is constrained by different confounding factors such as indications of specific medicines and the wide spectrum of medical conditions/diseases of patients from whom reporting of disproportionality ratios are derived (i.e. proportions of DECs for orphan drugs (ODECs) from a small patient population suffering the rare disease and the proportion of DECs in the rest of the population represented in the whole database who have been treated with other medicines for a wide range of indications, and prescribed to treat completely different medical conditions). As expected, these statistical calculations produced not only signals of disproportionate reporting (SDRs) that are false positives, but also not sensitive enough to detect certain SDRs, thus resulting in false negatives. In the context of rare/ultra-rare life-threatening diseases where new molecules have been made available on the market on the basis of their proven efficacy, but with only limited safety data at the time of approval, false negatives could be a special concern since unlikely converted in positives or becoming positives with notable delay. Subgroup analyses (using a limited dataset comprising ADRs within specific individual case safety reports (ICSRs), sorted by indication/disease relevant to the drug of interest could, at least in part, possibly reduce some of the weaknesses resulting from the abovementioned confounding factors. On the other hand it could also cause the loss of some identification of SDRs that would be captured if no database restrictions had been undertaken. Therefore, data subgroup analysis should not be selected as a preferred approach to quantitative signal detection for orphan drugs but rather evaluated as complementary possibly to confirm negatives or to further characterize detected SDRs. Some examples of false negatives originating from quantitative signal detection in EudraVigilance applied to orphan drugs are discussed in this article., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2019.)

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. This should also allow a clear view of data that are not available at any given time point and facilitates planning of strategies to obtain data through appropriate postmarketing risk management. Although it is not always easy, there are possibilities to increase the speed by which data in the postmarketing period can be generated by better use of data from ongoing formal clinical trials, by early planning of drug or disease registries and leveraging the power of both disease patient support groups, which are often well established, and networks to facilitate international research, specifically in rare diseases. The future may offer approaches using personal medical monitoring data tools and 'big data' to further facilitate the availability of information and to determine the effectiveness and safety profiles of drugs used for rare diseases and thus allow the benefit/risk of these drugs to be optimized. These issues will be discussed here., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

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. RPF-1 showed nuclear localization, elevated stability, and transactivation of promoters featuring POU consensus sites, and led to reduced cell proliferation and in vivo tumor growth. By addressing the whole transcriptome regulated by its induction, we could detect a gross alteration of gene expression that is consistent with promoter occupancy predicted by genome-wide Chip-chip analysis. Comparison of bound regulatory regions with differentially expressed genes allowed identification of 217 candidate targets. Enrichment of divergent octamers in predicted regulatory regions revealed promiscuous binding to bipartite POUS and POUH consensus half-sites with intervening spacers. Gel-shift competition assay confirmed the specificity of RPF-1 binding to consensus motifs, and demonstrated that the Ser-rich region upstream of the POU domain is indispensable to achieve DNA-binding. Promoter-reporter activity addressing a few target genes indicated a dependence by RPF-1 on transcriptional response. In agreement with its expression in developing kidney and nervous system, the induced transcriptome appears to indicate a function for this protein in early renal differentiation and neuronal cell fate, providing a resource for understanding its role in the processes thereby regulated., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., Areas Covered: This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included., Expert Opinion: DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

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. The aim of this study was to investigate the possible role of dopamine on the antidepressant-like effect of allopregnanolone in a model of depression. Thus, we examined (i) the behaviour of female Sprague-Dawley rats in the forced swimming test during estrus and diestrus and their response to allopregnanolone treatment (0.5, 1 and 2 mg/kg), and (ii) the effect of the dopamine D1-like and D2-like receptor antagonists SCH 23390 (0.01 and 0.025 mg/kg) and raclopride (0.05 and 0.2 mg/kg) on the antidepressant-like effect of allopregnanolone (2 mg/kg) in the same experimental model. We failed to observe differences in depressive-like behaviour between estrous phases, and allopregnanolone administration in both estrus and diestrus resulted in an antidepressant-like effect consisting in an increase of swimming behaviour. The allopregnanolone effect was unaffected by a dose of the dopamine D1-like receptor antagonist SCH 23390 displaying a marked inhibitory effect on basal activity, while it was turned into a potentiation of the depressive-like behaviour of the forced swimming condition by treatment with the higher dose of raclopride. The present results indicate an involvement of dopamine transmission in the allopregnanolone antidepressant-like effect in the forced swimming model of depression, and suggest that this effect depends mainly on stimulation of dopamine D2-like receptors.

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. Metal content was determined and high levels of potassium, sodium, iron, calcium and magnesium in carbonized and raw grape stalk were exhibited. This characteristic made difficult physical activation at high temperatures. A leaching step was included before the activation with steam, and adsorbents with surface areas between 700 and 900 m(2)/g were obtained. Physical activation was also performed at lower temperatures using carbonized grape stalk without leaching, leading to the development of some grade of porosity, with an area of 412 m(2)/g. These results would indicate the catalytic effect of the minerals present in this raw material. Chemical activation using phosphoric acid as activating agent seemed to be a very efficient method as final products with BET areas between 1000 and 1500 m(2)/g were obtained.

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.1105C>T), introducing a premature stop codon in exon 8 (p.Q369X), in a young XY male patient who presented with bilateral cryptorchidism, nystagmus, mild proteinuria and WT, but no sign of severe nephropathy. Although the majority of congenital urogenital abnormalities are not due to constitutional defects of the WT1 gene, our findings provide a rational for considering WT1 mutational analysis as one of the screening options in newborns with congenital defects of the urogenital tract due to the associated high risk of WT.

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. The aim of this study was to investigate the ability of selected tumor markers to discriminate BRCAX breast cancers from cancers arising in carriers of mutations in BRCA genes, and their usefulness in selecting familial cases in whom testing for such mutations is more likely to result uninformative. We carried out a morphological and immunohistochemical analysis on 22 BRCA1, 16 BRCA2 and 33 BRCAX familial breast cancers. Age at first diagnosis, histological type and grade, and immunostaining for estrogen receptor (ER), progesterone receptor (PR), p53, HER2/Neu, E-cadherin and cyclin D1 were investigated. The occurrence of somatic mutations of the TP53 gene was also verified. BRCA1 tumors resulted clearly distinguishable from BRCAX cases, occurring at a younger age, being more frequently of higher grade, negative for ER, PR and cyclin D1 expression and positive for p53 alterations. The predictive value of age at diagnosis, histological grade and PR expression was confirmed in a multivariable analysis. When comparing BRCA2 with BRCAX tumors, the only parameter that differed was cyclin D1, which was significantly overexpressed in BRCA2 cases both in the univariable and the multivariable analyses. If confirmed by further studies, our observations indicate that the investigation of cyclin D1 expression in familial breast cancer cases could be used, in conjunction with the analysis of other tumor markers preferentially associated with BRCA1 or BRCA2 tumors, to prioritize hereditary cases for mutation testing in BRCA genes.

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. Immunohistochemical study revealed the absence of nuclear expression of WT1 protein, while beta-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular investigations of WT1 gene and exon 3 of beta-catenin (CTNNB1) gene detected no mutations. At 4 years of age, 28 months after the chemotherapy completion, a third WT was diagnosed in the left kidney, and surgically removed before any further chemotherapy. Nine months after surgery, a metastasis was detected in the left lung. Both the third renal tumor and the lung metastasis showed a blastema-predominant morphology. Immunohistochemistry confirmed the lack of expression of WT1 protein, while beta-catenin protein was expressed at nuclear level by the large majority of tumor cells. Molecular analysis of the third renal tumor and the lung metastasis revealed a 4 bp deletion in exon 7 of WT1 gene, leading to a frameshift of the reading frame and to a premature stop of the translation (c.925_928delACTC, p.T309LfsX71); no mutations in the exon 3 of the beta-catenin gene were documented., Conclusions: These data demonstrate that multiple WTs can arise as a consequence of different genetic events in a patient with genetic predisposition, such as WAGR syndrome., ((c) 2008 Wiley-Liss, Inc.)

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. In situ RT-PCR demonstrated that Pou6f2 expression parallels the centripetal differentiation of renal morphogenesis. In addition, in E18 kidney, most structures exhibiting Pou6f2 expression stained positively in immunohistochemistry for the Wt1 protein. Finally, quantitative real-time RT-PCR revealed an overexpression (>/=80 times) of POU6F2 compared with normal kidney in 5 of 22 (23%) WTs. The finding of a highly regulated temporal and spatial Pou6f2 expression during renal organogenesis, of its coexpression with Wt1 and of POU6F2 overexpression in a subset of WTs are consistent with a role of POU6F2 in kidney development and provide further support to its involvement in WT.

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. The Italian CHAQ was already published in the literature and was therefore revalidated while the Italian CHQ was fully cross culturally adapted with 3 forward and 3 backward translations, and than validated. A total of 1,192 subjects were enrolled: 404 patients with JIA (16% systemic onset, 31% polyarticular onset, 21% extended oligoarticular subtype, and 32% persistent oligoarticular subtype) and 788 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Italian version of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

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 12.5 and persist throughout development both in the CNS and in some peripheral ganglia. Comparison of the expression patterns of the Kif3 genes revealed that Kif3c and Kif3a mRNAs colocalize in the CNS, while only Kif3a is also present outside the CNS. In contrast, Kif3b is detectable in several non-neural tissues. We have also performed immunocytochemical analyses of the developing rat brain and have found the presence of the KIF3C protein in selected brain regions and in several fibre systems. Using neuroblastoma cells as an in vitro model for neuronal differentiation, we found that retinoic acid stimulated the expression of the three Kif3 and the kinesin-associated protein genes, although with different time courses. The selective expression of Kif3c in the nervous system during embryonic development and its up-regulation during neuroblastoma differentiation suggest a role for this motor during maturation of neuronal cells.

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. Responsiveness of endpoint variables was evaluated by assessing the effect size (ES) and the standardized response median (SRM)., Results: Physician and parent global assessments were the more responsive instruments, showing ES and SRM above 1.0. Erythrocyte sedimentation rate, C-reactive protein, functional status measures and articular variables showed intermediate responsiveness. Morning stiffness, haemoglobin and platelet count were the least responsive instruments., Conclusion: The results of our analysis indicate that subjective estimations of the disease activity, either by the physician or parents, are the most responsive instruments in the assessment of the therapeutic response in children with JCA. The responsiveness of outcome measures in JCA should be further investigated in prospective controlled studies.

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. Display tags corresponding to 18 differentially expressed genes were cloned and, in most cases, identified as known genes or, more frequently, as their homospecific/cross-specific homologues. A novel member of the kinesin superfamily was identified amongst the genes induced by both 2ME and TGFbeta1. This gene, KIF3C, is upregulated in several cell lines undergoing growth arrest. Taken together, our findings show that computer-assisted gene fishing is a powerful tool for the identification and cloning of genes involved in the control of cell proliferation and indicate that extracellular reducing agents can regulate cell growth through modulation of gene expression.

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. Patients enrolled by each center were given MTX through the same method of administration. All patients received 10 mg/m2 of MTX each week for six months., Results: A total of 257 patients with JCA (127 treated orally and 130 intramuscularly) were enrolled in the trial by 11 Italian centers. The response rate after 6 months of MTX therapy was 58% in the oral and 61% in the intramuscular cohort. The frequency of adverse side effects did not differ significantly between the two treatment groups., Conclusion: The results of this study suggest that MTX at the conventional dose regimen is equally effective and has a similar safety profile in children with JCA when administered orally or by intramuscular injections.

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. Based on its high sequence similarity to the kinesin-like molecule KIF3B, we named this protein KIF3C. KIF3C is encoded by transcripts that are distinct from the KIF3B mRNA in human, rat, and mouse and is preferentially expressed in the brain. Fluorescence in situ hybridization reveals that, in the human genome, the KIF3C gene maps to chromosome 2 at 2p23. The sequence of KIF3C predicts an unusually long insertion in the proximity of L11, a region thought to mediate microtubule binding. Taken together, these findings suggest that KIF3C is a novel kinesin-like protein that might be specifically involved in microtubule-based transport in neuronal cells., (Copyright 1998 Academic Press.)

Deflazacort (DFZ), a new glucocorticoid which has recently become available, is expected to have less negative effects on growth and skeletal maturation than conventional steroids, in children treated long term. To verify this hypothesis, a multicentre trial was organized to evaluate the effects of DFZ vs prednisone (PDN) on statural growth and skeletal maturation in a group of prepubertal children requiring glucocorticoid therapy for at least 6 months/year. The results of an analysis of 55 children (aged 3-12 years, 24 with connective tissue disease and 31 with kidney glomerular disorders) treated randomly with either DFZ (31 patients) or PDN (24 patients) and followed for a mean period of about 22 months (16 months under steroid therapy) are presented. The observation period was split up into the following phases according to dose and administration regimen: daily, high-dose therapy; alternate-day, high-dose therapy; low-dose therapy; suspension of treatment. The height, statural age, skeletal age and body weight velocities (i.e. the increase/year) were considered. In spite of large intra-individual and inter-individual variability, the results suggest that DFZ has a lower negative impact on indicators of growth. During high-dose daily administration, the height velocity tended to be lower in the PDN group and the impairment of skeletal maturity was significantly less for DFZ than for PDN. During an alternate-day regimen, height velocity was slightly higher in the PDN group and skeletal age velocity was higher in the DFZ group. It seems that steroid effects on statural growth and bone maturation occur in parallel.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors assess the efficacy of gold salt treatment for juvenile rheumatoid arthritis. The study was carried out on 16 children suffering from mono-pauciarticular, polyarticular and systemic arthritis. Treatment consisted of the administration of auranofin alone in a group of 8 children and auranofin associated to corticosteroids in a second group of 8 children. A marked improvement in clinical conditions was observed with slight transitory side effects at follow-up after 12 and 24 months.

Deflazacort, a new glucocorticoid (DFZ) which has recently become available, is known to have lower adverse effects on the skeletal metabolism and is expected to inhibit growth to a lesser extent in long-term treated children than earlier cortisone analogues. With the aim of verifying this hypothesis a multicenter study was planned to compare the effects of deflazacort and prednisone on linear growth and skeletal maturation in a group of prepubertal children requiring chronic steroid therapy. The data presented in this interim analysis refer to 24 children (11 females and 13 males ranging in age from 2.4 to 11.8 yrs) with rheumatoid arthritis (18), systemic lupus erythematosus (4) or dermatomyositis, selected from the total sample of 65 subjects included in the trial. They were randomly allocated to DFZ or PDN treatment and received the minimum effective dose of either steroid for at least 6 months per year. Longitudinal height measurements were obtained with standard instruments and techniques, and the bone age was assessed according to Greulich and Pyle. The following indicators of growth retardation were considered: bone age delay (difference between bone age and chronological age), statural age delay (statural age, with respect to the 50th percentile minus the chronological age) and statural age loss (statural age with respect to the individual height percentile at the first observation minus the chronological age).(ABSTRACT TRUNCATED AT 250 WORDS)

A case of Schönlein-Henoch syndrome with neurological complications in a child is reported. Stress is laid on the fact that these symptoms were predominant throughout the course of the disease. Treatment, primarily based on cortisone, led to complete resolution of the neurological picture.