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A Stabile

Publications and source records attributed to A Stabile.

At least 19 recordsLinked to original sources
PubMed2006

Clinical and genetic characterization of Italian patients affected by CINCA syndrome.

OBJECTIVE: We report the experience of the Italian Registry of patients affected by chronic infantile neurological, cutaneous, articular (CINCA) syndrome. The clinical and genetic features of 12 unrelated Italian patients with CINCA syndrome are described, focusing on the possible influence of the presence of CIAS1/cryopyrin mutations on the phenotype of the disease and on its prognosis. METHODS: The clinical features of 12 Italian CINCA patients were evaluated. Genomic DNA of the patients was sequenced using specific primers for CIAS1 and ASC genes. RESULTS: Our patients shared typical CINCA characteristics and, sometimes, remarkable perinatal events, peculiar of CIAS1-mutated patients. Seven patients carried CIAS1 missense mutation, localized within the nucleotide binding domain of cryopyrin. Four previously described mutations and three new heterozygous CIAS1 missense mutations were identified. ASC gene, encoding for a direct interactor of cryopyrin, was not mutated in Italian CINCA patients. Finally, we reported the efficacy and safety of anti-IL1 therapy (Anakinra) in seven patients with a particularly severe CINCA phenotype. CONCLUSION: Despite some common signs-used as syndrome hallmarks-we observed a high variability in symptoms, genetic results and outcomes in Italian CINCA patients. In contrast with other authors, we cannot find out any correlation between mutations in CIAS1 and CINCA severity, but we underlined the concomitance of perinatal events and mental retardation only in CIAS1 mutated subjects. Finally, we confirmed the efficacy of Anakinra treatment, both in CIAS1-mutated and non-mutated patients.

Adolescent↗
PubMed2006

Hydrocephalus in CINCA syndrome treated with anakinra.

INTRODUCTION: Chronic infantile neurologic, cutaneous, articular (CINCA) syndrome is a rare congenital autoinflammatory disease characterized by neonatal-onset chronic meningitis, hydrocephalus, sensorineural hearing loss, persistent urticarial rash, deforming arthritis, and recurrent fever. This clinical entity is believed to result from dysregulation of cytokine production. No recommended treatment protocol exists so far for CINCA syndrome. CASE REPORT: We report a 7-year-old child affected with CINCA syndrome in whom no therapy had resulted effective. Anakinra, an interleukin-1-receptor antagonist, was administered in a 1-year period with complete inflammatory symptom remission and dramatically ameliorated laboratory tests. This optimal response has been supported by the demonstration of a stabilized hydrocephalus upon magnetic resonance imaging and by an overall improvement of the neurodevelopmental issues. DISCUSSION: This paper emphasizes and discusses the medical approach with anakinra in CINCA syndrome presenting with hydrocephalus in which a consistent control of the neurological picture can be obtained.

Arthritis↗
PubMed2004

[Risk factors conditioning the incidence and severity of cyclosporine A-induced gingival overgrowth and methods of prevention].

Cyclosporin A (CsA) induced gingival overgrowth is one of the major side-effects conditioning the quality of life of the patient under immunosuppressive therapy. This adverse effect has been first reported in 1983 and affects almost 30% of treated patients. Several papers have been published concerning the cellular/molecular mechanisms by which CsA may induce, at the same time, an immunosuppressive and proliferative action. In this review various factors concerning the patient and his milieu that account for the different prevalence of the severity of gingival overgrowth in clinical studies are analyzed and briefly discussed. In particular, age, sex, pharmacokinetic properties, pharmaceutical preparation, genetic predisposition, association with other drugs and the parodontal conditions before transplantation are considered. In addition, a unique approach to the patients with gingival overgrowth as well as effective methods of prevention and therapy are suggested.

Adolescent↗
PubMed2004

Diagnostic clues in the idiopathic pulmonary fibrosis of children.

Idiopathic pulmonary fibrosis (IPF) in children is a heterogeneous group of progressive disorders characterized by variable extents of inflammation and interstitial deposition of collagen fibers with numerous putative triggers. Children affected with this condition show breathlessness, non-productive cough and bibasilar/inspiratory dry rales. Diagnosis can be obtained by the exclusion of all known causes of fibrosing alveolitis such as neoplasms, toxic treatments, collagen vascular diseases, occupational exposure or granulomatous diseases.

Child↗
PubMed2004

Pharmacological strategies in the idiopatic pulmonary fibrosis of children.

Idiopathic pulmonary fibrosis is characterized by radiographically evident interstitial infiltrates and progressive dyspnea with rapid decline of overall lung functions. The clinical course of this disease is highly variable; however, its prognosis remains poor without adequate and prompt therapeutical support. Due to the fact that barely a quarter of patients responds to steroids alone, cytostatics are often prescribed simultaneously with low dose corticosteroids in the pediatric age too. Cytokine or anti-cytokine therapy and the role of new antifibrotic drugs are still at the experimental stage of definition and will be discussed in the following review.

Adrenal Cortex Hormones↗
PubMed2003

Etanercept induces improvement of arthropathy in chronic infantile neurological cutaneous articular (CINCA) syndrome.

Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare disorder of unknown aetiology with neonatal onset, characterized by severe arthropathy, persistent skin rash and central nervous system disease. Joint involvement may vary from minimal swelling to destructive arthritis, with inability to stand or walk. The most striking findings of CINCA syndrome are cartilage anomalies with epiphyseal modifications and abnormal ossification, for which a pathogenetic role of tumour necrosis factor-alpha (TNF-alpha) is postulated. We describe a 4-year-old child affected with CINCA syndrome and presenting progressive joint disease, in whom non-steroidal anti-inflammatory drugs (NSAID) and systemic corticosteroidal therapy had been ineffective. Etanercept, anti-TNF-alpha therapy, was administered over a 6-month-period resulting in a dramatic improvement of the arthropathy. This good response to anti-cytokine treatment supports our hypothesis that TNF-alpha might play an important role in the pathogenesis of CINCA syndrome, which needs to be evaluated and confirmed in further studies.

Antirheumatic Agents↗
PubMed2003

Conversion reaction presenting as a polyradiculonevritis.

AIM: To show that conversion reactions should be suspected when symptomatology or instrumental checking does not conform to a precise pathological pattern in its anatomical and physiological keys. METHODS: We report the case of a 14-y-old girl who presented with signs and symptoms of Guillain-Barré polyradiculonevritis. Negative instrumental and laboratory tests led us to consider a possible diagnosis of conversion reaction. RESULTS: After a more detailed history emphasizing the close bond between the patient and her father, a poor peer-relation exchange and psychological stress, we were able to identify conversion reactions through the patient's motor signs. CONCLUSION: Conversion symptoms must be suspected and searched for when the neurologic outline is difficult to clarify, and also in the case of Guillain-Barré syndrome that does not respond to plasmapheresis.

Adolescent↗
PubMed2000

Absorption and antithrombotic activity of unfractioned heparin after intraduodenal administration in rats.

In the search for a more acceptable route of heparin administration that can also be used for long-term treatment, we evaluated the bioavailability and antithrombotic activity of intraduodenal administration of unfractioned heparin (UFH) in rats. A radioiodinate derivative of UFH was administered intraduodenally in rats in conjunction with unlabeled UFH. We found that radioactivity increases very rapidly in plasma, as well as on the surface of aortic and caval segments, so that peak radioactivity was already achieved within 5 min of drug administration. Subsequently, plasma radioactivity declined rapidly, although 1.5-2.5% of the total radioactivity administered was still circulating 3 h after drug administration. The plasma anti-Xa activity was much lower and longer lasting than expected from the radioactivity counts in both peripheral and portal blood, and its level was very similar in the two circulatory districts, never exceeding 023 U/ml. This suggests that extensive degradation of the drug already occurs during its gastrointestinal absorption. Nevertheless, in a stasis-induced venous thrombosis model, intraduodenal UFH prevented thrombus formation in a dose-dependent way (ED50, 2000 IU/kg). The maximum antithrombotic effect was observed when the drug was administered 30-60 min before ligature of the vena cava, and a 40% reduction of thrombus weight was still present at 180 min. Since antithrombotic kinetics does not match the kinetics of either the plasma or vessel-bound radioactivity but approaches what is found in anti-Xa activity, the antithrombotic activity of oral heparin may be dependent on the release of unlabeled endogenous glycosaminoglycans deposited in the vessels.

Absorption↗
PubMed1999

Mononuclear cell reactivity to food allergens in neonates, children and adults.

A model of antigen-specific T-cell proliferative responses based on reciprocal patterns of responses to dietary and inhalant allergens has been suggested, the former being frequent in infancy but rare in adults, whereas the latter are preserved and expand between infancy and adulthood. We have evaluated the age-related variations of mononuclear cell reactivity to food allergens. The cord blood mononuclear cells (CBMC) of 30 neonates without family history of atopy and the peripheral blood mononuclear cells (PBMC) of 20 healthy children and of 40 healthy adults were stimulated in vitro with beta-lactoglobulin (BLG) or ovalbumin (OVA) and the cultures were harvested after 7 days. Neonates, children and adults were compared for the percentages of positive responses and for the magnitude of response. Adult subjects showed significantly lower percentages of positive responses and reduced magnitude of response than those observed in neonates and children either in BLG or in OVA cultures. We have not observed a decrease of food allergen mononuclear cell reactivity between neonates and children for the frequency of positive responses. The magnitude of response of neonates was significantly lower than that of children in BLG cultures. Our results seem to confirm the loss of mononuclear cell reactivity to food allergens in adult age. However, other reports show conflicting data. We suggest that a rigorous standardization of the methodological steps of in vitro mononuclear cell stimulation with allergen is necessary.

Adult↗
PubMed1994

Cord blood mononuclear cell responsiveness to beta-lactoglobulin: T-cell activity in 'atopy-prone' and 'non-atopy-prone' newborns.

We have studied the T-cell-mediated response to the major allergen of cow's milk, in a group of newborns at risk of developing cow's milk allergy, and in a control group. Before any atopic status has developed, we observe beta-lactoglobulin-specific primary proliferation only in the group at risk for food-related allergies. In this group, the capability to proliferate is not due to placental transmission of 'factors' from allergic mothers. The recognition of the tested beta-lactoglobulin peptides does not show major differences between the responder and nonresponder populations. In the responder population, the response to p145-161 appears linked to a primary response to ovalbumin, another frequent food allergen. On the basis of our findings, we propose a model in which development of allergic diseases is linked to an alteration of T-cell activation through the engagement by the antigen; the HLA phenotype determines the allergen(s) involved, and other genetic or environmental factors dictate the clinical characteristics of the disease.

Epitopes↗
PubMed1991

Immunodeficiency and plasma zinc levels in children with Down's syndrome: a long-term follow-up of oral zinc supplementation.

To evaluate the possible effect of zinc treatment on immune disorders in children with Down's syndrome (DS), 38 noninstitutionalized DS children were investigated. Twenty-four patients (63.2%) had plasmatic zinc levels lower than 0.70 microgram/dl ("hypozinkemic," LZn) and 14 patients (36.8%) had levels higher than 0.75 microgram/dl ("normozinkemic," NZn). No correlation was found between the zinc deficiency and recurrence and/or intensity of infections. The absolute numbers of peripheral lymphocytes, the percentages of B lymphocytes, total T cells, and serum IgG, IgA, and IgM levels did not differ between the DS children and the controls. Eight (21%) patients had CD4+ T cell counts below the lowest value for the controls. Seventeen (44%) DS patients had increased levels of CD8+ T cells. The mean percentage of Leu 7+ cells in DS subjects (22.8 +/- 12.9%) was significantly higher than that in controls (15.8 +/- 4.8%) (P less than 0.01). Notably, Ig levels and numbers of lymphocytes in each subset did not show any significant difference in NZn and LZn trisomic subjects. On the contrary the peripheral blood mononuclear cells (PBMCs) from LZn DS children showed a significantly lower proliferative response to phytohemagglutinin (PHA) (S.I. = 23.4 +/- 22.4) than that of PBMCs from NZn DS children (S.I. = 46.1 +/- 21.5, P less than 0.01). A significant increase in DNA synthesis was obtained after oral administration of zinc sulfate (20 mg/kg/day, for 2 months). The lymphocyte response to PHA appeared to be normal in all patients up to 6 months after the end of the zinc treatment and it became low in half of the patients 22 months after therapy.

Administration, Oral↗