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V De Sanctis

Publications and source records attributed to V De Sanctis.

At least 19 recordsLinked to original sources
PubMed2003

Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases.

Triggering of the Fas receptor induces T cell apoptosis and is involved in shutting-off the immune response. Inherited defects impairing Fas function cause the autoimmune lymphoproliferative syndrome, and may play a role in other autoimmune diseases. The aim of this work was to analyse the Fas function in paediatric patients with thyroid autoimmunities. We found that T cells from 24/28 patients with Graves' disease (GD) and 12/35 patients with Hashimoto's thyroiditis (HT) displayed defective Fas function. In HT, the defect was more frequent in patients requiring replacement therapy (11/20) than in those not requiring (1/15); moreover, in untreated HT the highest defect was displayed by patients with the highest levels of autoantibodies. Fas was always expressed at normal levels and no Fas mutations were detected. Analysis of the healthy parents of seven Fas-resistant patients showed that several of them were Fas-resistant, which suggests a genetic component. Fusion of Fas-resistant T cells with the Fas-sensitive HUT78 T cell line generated Fas-resistant hybrid cells, which suggests the presence of molecules exerting a dominant negative effect on Fas function. Analysis of Fas-induced activation of caspase-8 and -9 showed decreased activity of both caspases in HT, whereas activity of caspase-9 was increased and that of caspase-8 was decreased in GD. These data suggest that heterogeneous inherited defects impairing Fas function favour the development of thyroid autoimmunities.

Adolescent↗
PubMed2003

Growth and puberty in thalassemia major.

Present transfusional regimen protocols increase the life expectancy of patients with beta-thalassemia major, but cause a progressive iron overload that can be prevented or limited only by appropriate iron chelation. Siderosis is responsible for the clinical complications of the disease. Short stature and hypogonadism are extremely frequent in patients with thalassemia. Many factors are responsible for short stature in patients with thalassemia, the most important of which are dysfunction of the GH-IGF-I axis and desferoxamine (DFX)-induced bone dysplasia. Hypogonadism is the most frequent endocrine complication, mostly due to gonadotrophins deficiency secondary to iron overload. Sex steroid treatment for induction of puberty and/or maintenance of sexual characteristics is necessary. Both short stature and hypogonadism are present in a significant percentage of bone marrow transplanted patients with thalassemia. Factors responsible for short stature are previous iron overload, liver impairment, DFX treatment, and toxicity of chemotherapeutic agents. In some patients absence of pubertal development is due to gonadotropin insufficiency, probably secondary to previous iron overload; other patients exhibit hypergonadotrophic hypogonadism due to the toxic effect of chemotherapeutic agents on the gonads. Both groups need hormonal replacement therapy. These data support the need for vigilant follow-up of patients with thalassemia before and after transplantation, in order to treat endocrine dysfunctions at the appropriate age.

Body Height↗
PubMed2002

Regression of autoimmunity and abnormal glucose homeostasis in an adolescent boy with silent coeliac disease.

UNLABELLED: We report on a 15-y-old adolescent boy affected by silent coeliac disease, abnormalities in glycoregulation and with autoantibodies specific to diabetes mellitus type 1 (ICA: islet cell antibodies) and GAD 65 (autoantibodies against glutamic acid decarboxylase), in whom normalization of glycoregulation and disappearance of the immunological markers of pre-diabetes were observed after 6 mo on a gluten-free diet. The patient was followed-up for 36 mo and showed a normal insulin response to an intravenous glucose tolerance test and no markers of autoimmunity. It is possible that undiagnosed coeliac disease over a long period could lead to a direct autoimmune mechanism against pancreatic beta cells. CONCLUSION: Our findings seem to confirm the theory that undiagnosed coeliac disease can induce an autoimmune process against the pancreatic beta cells and that, following a gluten-free diet, the immunological markers for diabetes mellitus type 1 will disappear.

Adolescent↗
PubMed2002

Growth and puberty and its management in thalassaemia.

The purpose of this review is to report the personal experience on growth and pubertal development in a large number of thalassaemic and ex-thalassaemic patients followed at the Pediatric and Adolescent Unit of Ferrara. Secondary amenorrhoea (SA), hypogonadism and short stature are the commonest endocrine and auxological complications. The anterior pituitary gland is particularly sensitive to free radical oxidative stresses and exposure to this. Magnetic resonance imaging (MRI) shows that even a modest amount of iron deposition within the anterior pituitary can interfere with its function. Other possible cause of hypogonadism in beta-thalassaemia major include liver disorders, chronic hypoxia, diabetes mellitus and zinc deficiency. The treatment of pubertal disorders consists of hormone replacement therapy with sex steroids. Successful induction of spermatogenesis and ovulation has been reported after hormonal stimulation with gonadotrophins. Height above the 10th centile was achieved in 50% of males and 64% of females. Eight prepubertal thalassaemic patients, 6 males and 2 females, ranging in age from 8.6 to 11.7 years, were treated with GH. After the first 12 months of GH treatment a significant increase of growth velocity was observed in 6 patients who doubled growth velocity before basal value (4 cm or more above the basal value), 2 patients had a partial response (2-4 cm above the basal value). In the following 3 years all thalassaemic patients had a partial response to the treatment with GH. These data indicate that despite somewhat reduced sensitivity to GH, compared to GH deficiency children, there is evidence indicating that thalassaemic patients may benefit from GH treatment. Sixty-eight thalassaemic patients (30 males and 38 females) who had successfully undergone bone marrow transplantation (BMT) during childhood were studied. Following BMT growth rate decelerated when compared to Tanner and Whitehouse standards. Twenty-nine ex-thalassaemics reached final height. The patterns of growth during puberty was variable in ex-thalassaemic males, while in all but 3 ex-thalassaemic females we observed an improvement in the percentile of standing height. A gonadal dysfunction was found in 68% of ex-thalassaemic patients. Since the quality of life of these patients is an important aim, it is vital to monitor carefully the growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment.

Adolescent↗
PubMed2002

Thyroid nodules.

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Biopsy, Needle↗
PubMed2002

Hypothyroidism.

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Humans↗
PubMed2002

[Chest pain in adolescents].

In children and in adolescents, chest pain is relatively common and self-limiting. The close association between chest pain, cardiopathies and sudden death is the cause of intense anxiety in boys and their parents and even doctors. The most frequent causes of chest pain, the diagnosis and the eventual treatment are examined. Finally, the causes of chest pain due to drug abuse (in particular cocaine) and to CO poisoning are also examined. Good knowledge of the problem, an accurate anamnesis and a careful objective exam are useful to choose the most suitable treatment.

Adolescent↗
PubMed2002

[Asthenia in adolescents].

Fatigue is defined as a subjective sensation of tiredness or weariness that occurs at rest. The perception of fatigue among 12-15 years-old Italian adolescents in a school survey was about 70%. Generally the symptoms are reported after a viral illness or an infection. In adolescents with persistent or severe fatigue a selected screening evaluation to look for an underlying organic disorder is warranted. A practical diagnostic approach is given and a brief description of chronic fatigue syndrome is reported according to CDC revised diagnostic criteria published in 1997.

Adolescent↗
PubMed2001

Characterization of pseudoxanthoma elasticum-like lesions in the skin of patients with beta-thalassemia.

BACKGROUND: Pseudoxanthoma elasticum (PXE), an inherited disorder of unknown pathogenesis, is characterized by elastic fiber mineralization, collagen fibril alterations, and accumulation of thread material in the extracellular space. PXE-like clinical lesions have been described in patients with beta-thalassemia. OBJECTIVE AND METHODS: Dermal lesions in these two genetic disorders were compared by light and electron microscopy and by immunocytochemistry. RESULTS: In both disorders, elastic fiber polymorphism, fragmentation, and mineralization were structurally identical. Elastic fiber mineralization in beta-thalassemia was associated with vitronectin, bone sialoprotein, and alkaline phosphatase, similar to what was observed in inherited PXE. Furthermore, abnormalities of collagen fibrils and filament aggregates were identical in both disorders. In both inherited and beta-thalassemia-associated PXE, unrelated gene defects seem to induce cell metabolic abnormalities that lead to identical clinical and structural phenotypes. CONCLUSION: Data indicate that patients with beta-thalassemia may undergo important alterations of connective tissues, a better understanding of which may help in preventing clinical complications.

Adult↗
PubMed2001

Management of puberty for optimal auxological results in beta-thalassaemia major.

Short stature is present in a significant percentage of patients affected by beta-thalassaemia major. Growth failure of patients with thalassaemia is multifactorial. The most important contribution is attributed to the toxic effect of desferrioxamine and to endocrine disorders, due to iron overload. The commonest endocrine complication is hypogonadism. The growth pattern of patients with thalassaemia is characterized by normal growth during childhood, a deceleration of growth velocity around age 9-10 years, and a reduced pubertal growth spurt. In addition, reduced growth of the trunk is often present. Short stature and short trunk are more evident at pubertal age. Hypogonadism is usually considered responsible for the pubertal growth failure, as well as the aggravation of body disproportion at pubertal age. However, data suggest that pubertal height gain and final height are reduced in both patients with spontaneous puberty and patients with induced puberty. It is concluded that several aspects of peripubertal growth in patients with thalassaemia remain to be clarified.

Adolescent↗
PubMed2001

Unresolved problems in optimal therapy of pubertal disorders in oncological and bone marrow transplanted patients.

Specialised clinics for the long-term follow-up of survivors from childhood cancer have developed over recent years. The problems encountered among patients who received multiple chemotherapy and radiotherapy can be challenging and require high expertise and close collaboration among different professionals (e.g. oncologists, endocrinologists, radiotherapists, psychologists). Endocrine disorders are often seen, particularly among those who received cranial radiotherapy or gonadotoxic chemotherapy; puberty can be affected and the spectrum of disorders may range from precocious or accelerated puberty to delayed, arrested or even absent pubertal development. Growth impairment can be multifactorial and growth hormone deficiency is an important but probably not the only factor involved. Many questions remain about the optimal management of this group of young patients. In the consensus guidelines that follow the overview an attempt is made to help optimise patients' growth and puberty by suggesting practical clinical approaches to some of the most challenging issues.

Adolescent↗
PubMed2001

Cardiovascular haemodynamics and cardiac autonomic control in patients with subclinical and overt hyperthyroidism.

OBJECTIVE: To characterize cardiac structure and function and cardiac autonomic control in patients with subclinical and overt hyperthyroidism. DESIGN: Thirty patients with subclinical hyperthyroidism and 30 with overt disease were selected from patients never previously treated for endocrinological disease in the outpatient clinic of our institution. Twenty normal individuals were studied as control group. METHODS: Left ventricular structure and function and cardiac autonomic control were evaluated, respectively, by two-dimensional Doppler echocardiography and by 24-h Holter recording with heart rate variability analysis. RESULTS: Patients with overt hyperthyroidism showed greater values of left ventricular end-diastolic volume (P<0.05) and left ventricular mass (P<0.05) than patients with subclinical disease. In addition, the mean velocity of left ventricular fibre shortening (P<0.05) and left ventricular ejection fraction (P<0.05) were greater in patients with overt hyperthyroidism than in patients with subclinical disease. No difference in any of these parameters was detectable between normal subjects and patients with subclinical disease. The isovolumic relaxation period was shorter in patients with subclinical hyperthyroidism than in control individuals (P<0.05) and in patients with overt hyperthyroidism (P<0.05). As regards cardiac autonomic control, all time and frequency domain measures decreased progressively from control individuals to patients with subclinical hyperthyroidism and those with overt disease (P<0.001). CONCLUSIONS: Thyrotoxic patients show changes in left ventricular structure and increased echocardiographic indexes of myocardial contractility, whereas the only echocardiographic feature detectable in patients with subclinical hyperthyroidism is an increased velocity of left ventricular relaxation. Cardiac parasympathetic withdrawal is evident in patients with overt hyperthyroidism and in patients with subclinical disease.

Adult↗
PubMed2001

Cell cycle arrest determines the intensity of the global transcriptional response of Saccharomyces cerevisiae to ionizing radiation.

Whole-genome analysis was performed using DNA microarrays to define the changes in the gene expression patterns occurring in Saccharomyces cerevisiae cells exposed to ionizing radiation. The effects of sublethal dose on wild-type, rad53 (enhanced sensitivity to radiation and impaired in a cell cycle damage checkpoint), and rad6 (enhanced sensitivity to radiation and functional cell cycle block by radiation) mutant backgrounds and of a higher dose on the wild-type and G(2)-phase-arrested cells were analyzed. Several gene pathways were identified as being implicated in the response to radiation. In particular, the cell cycle blockage that occurred in the wild-type strain after a high radiation dose and in the rad6 mutant after a lower dose entailed modifications of defined gene expression patterns, which are described here and are compared with the gene modulation patterns observed in the rad53 strain in the absence of efficient blockage. Loss of the RAD53 function caused a major increase in the number of genes modulated by radiation. Given that Rad53-Sad1p, the protein encoded by RAD53, has functions other than those directly connected to cell cycle arrest, we determined the gene patterns that were modulated upon irradiation of rad53 cells that had been forced to arrest in G(2) phase by nocodazole treatment. These differential whole-genome analyses shed light on the multiplicity of functions of the pivotal Rad53-Sad1p protein. The results obtained describe how the cells respond to different irradiation conditions by modulating important gene classes, including those associated with stress defense, ribosomal proteins, histones, ergosterol and GCR1-controlled sugar metabolism.

Cell Cycle↗