Inflammatory biomarkers and intellectual disability in patients with Down syndrome.

BACKGROUND: Intellectual disability (ID) is part of the Down syndrome (DS) phenotypic spectrum, but the exact molecular pathophysiology of ID in individuals with DS is not yet fully understood, with many research hypotheses still unproven. Basing on previous studies (which suggested a possible role of altered inflammatory response in DS-related ID), we assessed the serum levels of a number of inflammatory biomarkers [serum amyloid A (SAA), C-reactive protein (C-RP), high mobility group box-1 (HMGB1)] in a cohort of individuals with DS and healthy controls. METHODS: In total, 24 children diagnosed with DS and 12 healthy controls were enrolled, and all underwent detailed cognitive assessment. Also, serum SAA, C-RP and HMGB1 levels were measured in all recruited subjects and correlated to the severity of ID in the DS group. RESULTS: Serum SAA, C-RP and HMGB1 values were found to be significantly higher in the DS group compared with the healthy subjects (P = 0.001). In addition, serum HMGB1 levels positively correlated with C-RP and SAA in the DS group but not in the healthy controls. Only serum C-RP levels resulted inversely correlated (P < 0.01) with intelligence quotient (IQ); conversely, significant statistical correlations between serum SAA levels and IQ (as well as between HMGB1 and IQ) have been not found (P > 0.05). CONCLUSIONS: The levels of the determined markers were higher in DS individuals compared with (cognitively) healthy subjects, and CRP showed a negative correlation with IQ in children with DS.

Association between maternal serum high mobility group box 1 levels and pregnancy complicated by gestational diabetes mellitus.

BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM), is characterized by chronic, low-grade subclinical inflammation with altered production of cytokines and mediators. Recently, a new protein acting as a "danger signal", high mobility group box 1 (HMGB1), that migrates quickly during electrophoresis, has been identified. The aim of our study was to analyze serum levels of HMGB1 in pregnant women, with or without GDM, in the third trimester of pregnancy to evaluate correlation with insulin resistance and other risk factors for GDM. METHODS AND RESULTS: Seventy five pregnant women positive to the 75 g oral glucose tolerance test (OGTT) were included in the study group and 48 pregnant women who were negative to the screening test, were randomly selected using a computer-generated randomisation table. A significant positive univariate correlation was observed between serum HMGB1 levels, HOMA-IR index, glycaemia values at OGTT and pre-pregnancy BMI. Moreover, logistic regression analysis showed that serum HMGB1 was independent linked to GDM. CONCLUSION: Our study demonstrated that HMGB1, a marker of chronic inflammation, is associated to GDM and insulin resistance level, in the third trimester of pregnancy.

The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features.

Spinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non-SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271).

PRIMARY NOCTURNAL ENURESIS IN CHILDREN WITH ALLERGIC RHINITIS AND SEVERE ADENOTONSILLAR HYPERTROPHY: A SINGLE CENTER PILOT STUDY.

Nocturnal enuresis is defined as intermittent urinary incontinence during sleep that occurs at least twice a week for three consecutive months. There is no unifying etiology for nocturnal enuresis in the pediatric population and the disorder is likely to be multifactorial. We aimed to investigate the relationship between primary nocturnal enuresis, allergic rhinitis, and related complications in a paediatric case series from a single Center. We retrospectively reviewed and prospectively followed-up at our Institution (i) 32 children (14 females, 18 males; mean age 6.31±1.21 yrs) affected by allergic rhinitis with adenoidal hypertrophygrade I-II (group A) and (ii) 27 children (11 females, 16 males; mean age 6.52±1.33 yrs) affected by allergic rhinitis with adenoidal hypertrophy grade III-IV (group B). Allergic rhinitis was diagnosed on the basis of (a) typical nasal symptoms due to atopic sensitization (e.g., rhinorrhea , itching, sneezing fits, and nasal congestion and obstruction) and (b) positive skin prick testing and/or increased level of total serum IgE. We identified discrepancies between group A and group B in terms of risk of primary nocturnal enuresis. In fact, only 1 child of group A (3.12%) reported uncomplicated primary nocturnal enuresis; conversely, 6 children of group B (22.22%) showed a history of uncomplicated primary nocturnal enuresis (p=0.040). There was no statistically significant difference between the two groups in terms of atopic sensitization and serum total IgE levels (p=0.43). Allergic rhinitis may potentially influence the onset and the natural history of nocturnal enuresis in some children. Children with allergic rhinitis and more severe respiratory manifestations, seem to be more prone to developing primary nocturnal enuresis, likely due to potential multi-factorial causes (e.g., sleep disorders, chronic phlogosis, immune deregulation).

Central precocious puberty: from physiopathological mechanisms to treatment.

Puberty is a complex, coordinated biological process with multiple levels of regulations. The timing of puberty varies greatly in children and it is influenced by environmental, endocrine and genetic factors. Precocious puberty (PP) is an important issue, affecting between 1 in 5.000-10.000 children. The physiopathological mechanism is still unknown. From an etiological point of view, PP may be subdivided into gonadotropin-releasing hormone (GnRH) -dependent and independent causes. GnRH-dependent PP, often called central precocious puberty (CPP), is based on hypothalamic-pituitary-gonadal axis activation associated with progressive pubertal development, accelerated growth rate and advancement of skeletal age. Conversely, peripheral precocious puberty (PPP) is related to sex steroid exposure, independently of hypothalamic-–pituitary-–gonadal (HPG) axis activation. Kisspeptins play a central role in the modulation of GnRH secretion with peripheral factors that influence the timing of puberty, such as adipokines and endocrine disrupting chemicals. Moreover, PP could be related to genetic disorders, involving pivotal genes of the HPG axis. The standard test used to verify HPG activity is the gonadotropin response to administered GnRH analogs. We describe the physiopathological mechanisms of PP and its clinical implications, analysing diagnostic flow-chart and new potential biomarkers that could reveal PP. An update of the current literature was also carried out regarding the recent novelty for treatment.

Airways allergic inflammation and L. reuterii treatment in asthmatic children.

Recently, it has been hypothesized that the oral administration of specific live probiotic strains may have therapeutic potential in the treatment of allergic inflammation. The aim of this study was to evaluate the effect of the oral L. reuteri DSM 17938 administration (1X108CFU), in airways allergic inflammation in mild persistent asthmatic children. In this DBPC randomized study we selected 50 children (6-14 years old), affected by mild persistent asthma (GINA step 2) and allergic to HDM. At the run-in period (T-2), the children were submitted to medical examination, prick tests for the main respiratory allergens, spirometry and children asthma control test (C-ACT). We selected only the children with well controlled asthma (C-ACT >19 and FEV1> 80%). After two weeks (T0) the children were allocated into two groups, the FeNO was measured and the breath condensate was collected. Group A children were treated with the placebo (5 drops per day) and Group B children with L. reuteri (108CFU =5 drops per day) for 60 days. After the treatment period (T1), all patients were evaluated by medical examination, C-ACT, spirometry, FeNO measurement and exaled breath condensate analysis. The FeNO values showed a significant reduction (p=0,045) in L. reuteri group but not in the placebo group at the end of the treatment (T1). Furthermore, the cytokines exam showed an increase in IL-10 levels (p less than 0.05) and a significant reduction in IL-2 levels (p less than 0.05) only in L. reuteri group at T1. No significant differences in FEV1 values and C-ACT score were found in both groups. In conclusion, these data showed that L. reuteri (108 CFU) was effective in reducing bronchial inflammation in asthmatic children. No significant effect was found on FEV1 values and C-ACT score, probably because we selected children with well controlled asthma.

Probiotics and Helicobacter pylori infection in children.

Approximately 50 percent of the world population is infected with Helicobacter pylori (H. pylori), with the highest prevalence rates in developing countries. The current guidelines suggest the use of triple therapy as first choice treatment of Helicobacter pylori infection, although the eradication failure rate is more than 30 percent. Current interest in probiotics as therapeutic agents against Helicobacter pylori is stimulated by the increasing resistance of pathogenic bacteria to antibiotics, thus the interest for alternative therapies is a real actual topic. Available data in children indicate that probiotics seem to be efficacious for the prevention of antibiotic associated side-effects, and might be of help for the prevention of Helicobacter pylori complications by decreasing Helicobacter pylori density and gastritis, and for the prevention of Helicobacter pylori colonization or re-infection by inhibiting adhesion to gastric epithelial cells. There is no clear evidence that probiotics may increase the Helicobacter pylori eradication rate.

Atopy as a risk factor for thyroid autoimmunity in children.

Recently, there has been considerable interest in the relationship between allergic and autoimmune diseases. We evaluated the prevalence of thyroid autoimmunity in 566 children affected by atopic dermatitis (AD), urticaria, rhinitis, chronic cough, and asthma. Our results suggest that allergy and autoimmunity can be two potential outcomes of dysregulated immunity. It is tempting to speculate that NK Th2 cells can favour asthma onset and at the same time improve thyroid autoimmunity.

Human pulmonary dirofilariasis: report of a new European case.

We report a new European case of pulmonary dirofilariasis occurring in an Italian patient. The paper emphasizes the peculiar pathological features of Pulmonary Dirofilariasis, that, on clinical and radiological grounds, closely imitates primary or secondary neoplasms. The disease characteristically presents itself as a solitary subpleural coin-like lesion, histologically corresponding to a well demarcated, roughly spherical infarct, centered by a medium-sized thrombosed artery whose lumen contains the parasite, i.e. a Dirofilaria nematode.

[Markers of viral hepatitis B. Diagnostic, prognostic and therapeutic relevance]. / I markers della virus-epatite B. Rilevanza diagnostica, prognostica e terapeutica.

Analysis of the behaviour and chronological development of B virus markers (including those most recently identified) in acute and chronic hepatitis gives rise to a diagnostic hypothesis about their presence and association. The prognostic and therapeutic significance of the markers is also emphasised with particular reference to fulminating and chronic active HBSAg and D positive hepatitis and the early diagnosis of liver cell carcinoma.

[Benign monoclonal gammopathies: probable antibody specificity of monoclonal immunoglobulins]. / Gammopatie monoclonali benigne: probabile specificità anticorpale delle immunoglobuline monoclonali.

40 patients with benign paraproteinemia have been studied in relation to their age and associated diseases. Significantly high frequency of liver diseases (CALD, cirrhosis, hepatoma, metastases) has been found (12 over 40 people) and increased incidence of idiopathic paraproteinaemia in the old age has been confirmed. 9 patients have been followed for 5 years, so that one could be sure that they had really benign paraproteinaemia: these patients have been then studied from an immunological point of view, in vivo by means of skin tests (PPD, Candida, Trichophyton, DNCB) and in vitro by searching for circulating immune complexes (using a new highly specific immuno-enzymatic method), and compared to controls without paraproteinaemia. Highly positive skin tests have been found only in 7 over 9 patients (even in old subjects) and 6 of them had circulating immune complexes (C.I.C.) in their sera; all the controls were negative both for skin tests and for C.I.C. Immune complexes have been found also in some cases of idiopathic paraproteinaemia, so that they do not seem to be in relation to the associated diseases. The Authors suggest that a genetically determined defect in regulator/suppressor T lymphocyte activity may cause the growth of a benign B cell neoplasm; and that monoclonal immunoglobulins most probably have antibody specificity and are directed against target antigens.

[Obstructive peripheral athero-arteriosclerotic vascular diseases. Apparent pathogenetic role of hormono-metabolic changes]. / Vasculopatie periferiche ostruttive atero-arteriosclerotiche. Apparente ruolo patogenetico di alcune alterazioni ormono-metaboliche.

We determined by comparison, in 30 patients with arteriosclerosis obliterans and in 10 normal peoples, 50-70 years aged, the values of some glycolipidic parameters (blood glucose, triglyceridemia, cholesterolemia, nephaemia, beta- and pre-beta-lipoproteinemia) and moreover the hormonal ones (IRI, GH, cortisolemia) at fast in the morning, during the whole day and during some blocking and stimulating tests. Patients with arteriosclerosis obliterans presented a significant alteration of the lipidic outline (hyper-lipoproteinemia of IV type sec. Fredr) and of the carbohydrate metabolism, emphasized at the OGTT by a dissimilar tolerance (normal, borderline and pre-diabetic type) referring to a normal high and low insulin immission respectively. We dissert widely about biohumural data, as reflexes involved from the pancreatic function and from the ischaemic process, and we report the eventual tie between the detected hormone-metabolic disorders and the development of arteriosclerotic occlusive disease in the lower extremities.

LMNA gene mutation as a model of cardiometabolic dysfunction: from genetic analysis to treatment response.

AIM: This report highlights the metabolic, endocrine and cardiovascular comorbidities in a case of familial partial lipodystrophy (FPLD), and also evaluates the efficacy and safety of metformin therapy. METHODS: Mutational analysis was carried out of the LMNA gene in a teenage girl with an FPLD phenotype. Insulin resistance, sex hormones and metabolic parameters were also evaluated, and echocardiography, electrocardiography and 24-h blood pressure monitoring were also done. RESULTS: The patient showed atypical fat distribution, insulin resistance and hypertrophic cardiomyopathy. Physical examination revealed muscle hypertrophy with a paucity of fat in the extremities, trunk and gluteal regions, yet excess fat deposits in the face, neck and dorsal cervical region. LMNA sequencing revealed a heterozygous missense mutation (c.1543A>G) in exon 9, leading to substitution of lysine by glutamic acid at position 515 (K515E). Moderate hypertension and secondary polycystic ovary syndrome were also assessed. Treatment with metformin resulted in progressive improvement of metabolic status, while blood pressure values normalized with atenolol therapy. CONCLUSIONS: Very rapid and good results with no side-effects were achieved with metformin therapy for FPLD. The association of an unusual mutation in the LMNA gene was also described.

[Spontaneous mediastinal hematoma during therapy with oral anticoagulants]. / Ematoma mediastinico spontaneo in corso di terapia anticoagulante orale.

Mediastinal haematoma as a complication of anticoagulant therapy has rarely been described in the literature. A case is reported of an anterior mediastinal haematoma which developed in a patient with mitral valve disease while on oral anticoagulant therapy. This occurred in spite of well-controlled anticoagulation therapy and the clinico-radiological features did not directly recall the hemorrhagic complication. Computerized tomographic scan of the chest, even if not conclusive, was essential for the clinical strategy. A definite diagnosis was obtained by percutaneous needle aspiration followed by iodinate contrast medium injection. This procedure also led to the resolution of the haematoma, thus avoiding hazardous surgical therapy.

[Non-invasive evaluation of left ventricular function in chronic alcoholics. Histo-morphological and echo-polygraphic correlations]. / Valutazione non invasiva della funzione ventricolare sinistra in alcoolisti cronici. Correlazioni isto-morfologiche ed eco-poligrafiche.

Alcohol decreases myocardial contractility through direct, toxic effect. Ingestion of more than 150 g per day for more than 10 years carries a high risk of developing alcoholic cardiomyopathy. The discontinuance of alcohol intake--if put into effect early in the natural history of patients with alcoholic cardiomyopathy--commonly but not invariably results in remission of heart failure. In order to evaluate the left ventricular (LV) function and to find out a possible correlation between the degree of cardiac dysfunction and the severity of the morpho-functional aspects of alcoholic liver disease, 20 chronic alcoholic patients without clinical evidence of heart disease were examined. Echocardiography, systolic time intervals, mechanical polygraphic recordings and liver biopsy were obtained. According to the morphological alterations showed by the needle biopsy of the liver, we separated 12 patients with liver steatosis (Group I) from 8 subjects with alcoholic hepatitis and fibrosis. In Group I LVET, ICT, PEP/LVET indices and LV fractional shortening (delta %) were not statistically different from control subjects. Patients of Group II showed marked impairment of myocardial function, as revealed by significant ICT, PEP, PEP/LVET prolongation and by an equally significant reduction of fractional shortening of the LV. The noninvasive method has proved to be quite useful in detecting early LV dysfunction in asymptomatic chronic alcoholics and has revealed a correlation between the severity of the morphological involvement of the liver and the impairment of cardiac performance.