Minimum effective betamethasone dosage on the neurological phenotype in patients with ataxia-telangiectasia: a multicenter observer-blind study.

BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is a rare neurodegenerative disease, due to A-T mutated (ATM) gene mutations, which typically presents with signs of progressive neurological dysfunction, cerebellar ataxia and uncoordinated movements. A-T severely affects patients' quality of life. Successful treatment options are still not available. The aim of this multicenter study, performed with a blind evaluation procedure, was to define the minimal effective dosage of oral betamethasone, thus preventing the occurrence of side effects. METHODS: Nine A-T patients were enrolled to receive betamethasone at increasing dosages of 0.001, 0.005 and 0.01 mg/kg/day. Neurological assessment and the evaluation of quality of life were performed through the Scale for the Assessment and Rating of Ataxia and the Italian version of the Childhood Health Assessment Questionnaire (CHAQ) at each time-point. The drug safety profile was evaluated. Patients were categorized as responders, partial responders and non-responders. RESULTS: Four of nine patients had a benefit at a dose of 0.005 mg/kg/day of oral betamethasone. Using the higher dosage, only one additional patient had a positive response. Conversely, a daily dose of 0.001 mg/kg was ineffective. A correlation between the serum adrenocorticotropic hormone levels and the clinical response was observed. Five of 30 CHAQ items improved in four patients. CONCLUSIONS: These data suggest that a short-term betamethasone oral treatment, at a daily dosage of 0.005 mg/kg, is effective in some patients. Pre-existing risk factors for side effects should be taken into account before therapy.

Evolution of hypogammaglobulinemia in premature and full-term infants.

There are few data in the literature reporting the evolution of hypogammaglobulinemia in premature and full-term infants during the first years of life. The aim of this study was to assess the clinical and immunological evolution of premature and full-term infants with hypogammaglobulinemia. We included 24 children (11 premature and 13 full-term infants), aged 0-36 months, with hypogammaglobulinemia. Fifteen (62.5%) children had an isolated reduction in IgG, 7 (29.2%) had a decrease in both IgG and IgA and 2 (8.3%) a reduction in IgG and IgM. Normalization of IgG serum levels occurred in the premature infants at a mean age of 7.2 months. Full-term infants were divided into 3 groups based on age at normalization of IgG serum level: A) hypogammaglobulinemia with normalization within 12 months of life; B) with normalization within 36 months of life; C) normalization after 36 months. All the premature infants with hypogammaglobulinemia recovered, even though in the lower limits for age in the first years, while transient hypogammaglobulinemia observed in full-term infants has a different age of recovery.

The effect of gamma-linolenic acid on clinical status, red cell fatty acid composition and membrane microviscosity in infants with atopic dermatitis.

A double blind placebo-controlled study of two doses of gamma-linolenic acid, provided by evening primrose oil (EPO, Epogam, Searle, U.K.), in children with atopic dermatitis was performed: 1) to examine the effect of gamma-linolenic acid administration on the clinical status of children with atopic dermatitis and abnormalities of IgE-mediated immune responses compared to those without such IgE abnormalities; 2) to investigate the effect of gamma-linolenic acid on red cell fatty acid composition and 3) to assess whether treatment with gamma-linolenic acid induced changes in red cell membrane microviscosity. A significant improvement in the overall severity of the clinical condition was seen in children treated with gamma-linolenic acid, independent of whether the children had manifestations of IgE-mediated allergy. Furthermore, gamma-linolenic acid treatment increased the percentage content of n-6 fatty acids in erythrocyte cell membrane; this increase was more marked in the membranes of children treated with high doses of EPO. In the high dose group a significant increase in dihomogamma-linolenic acid (DGLA) occurred. This may be of particular relevance because of the potential importance of DGLA as a precursor of antiinflammatory prostanoids. Red cell membrane microviscosity did not change in any group after treatment with EPO, even in high doses, despite a significant increase in the proportion of long chain polyunsaturated fatty acids.

[Evaluation of atopy risk factors during the first year of life. Multicentric study]. / Valutazione dei fattori di rischio di atopia nel 1 degree anno di vita. Ricerca policentrica.

The AA studied 406 newborn babies during the 1st year of life in order to verify the correlation between atopy risk factors and the appearance of early symptoms, particularly gastroenteric (GE). The results obtained did not demonstrate a significant difference concerning the blood cord IgE level and subsequent appearance of food allergy symptoms, whereas positive familiarity showed a better correlation. No significant difference was observed between breast--or formula--fed infants, or between those weaned before or after the 5th month of life. The comparison of dietary regimen adopted during the 1st quarter in the asymptomatic and atopic children respectively, demonstrated that the presence of predisposing factors influences the appearance of GE symptoms much more than the diet in itself. An allergologic study, randomly performed by Prick-test in 156 cases and by RAST in 200 cases, showed a prevalent, positive response with RAST technique in symptomatic children.

Are acute subdural hematomas possible without head trauma?

Acute subdural hematomas (ASDHs) are rarely reported in the literature. In general, it is due to head trauma, but if the traumatic event is very mild, it is inadequate to explain the ASDH occurrence. Risk factors for the development of spontaneous ASDH include hypertension, vascular abnormalities and deficit of coagulation. We present two cases of ASDH in patients with the coagulation deficit and review of the literature to understand the coagulation factors role and platelet role in the management of ASDHs.

Molecular biology of gliomas: present and future challenges.

Malignant brain tumours are one of the most relevant causes of morbidity and mortality across a wide range of individuals. Malignant glioma is the most common intra axial tumor in the adult. Many researches on this theme brought advances in the knowledge of gliomas biology and pathogenesis and to the development of new agents for targeted molecular therapy. Recent studies focused on either tumor metabolism analysis or epigenetic regulation in the pathogenesis or maintenance of brain tumors. This Review summarizes these developments analyzing molecular pathology and possible further developments for targeted therapies.

The natural history of sensitizations to food and aeroallergens in atopic dermatitis: a 4-year follow-Up.

The natural history of atopic dermatitis (AD) is variable. Generally the dermatitis disappears during the first years of life, but it is often followed by the appearance of allergic respiratory diseases (ARDs). Our aim was to establish the risk factors for developing an ARD in children with AD. We followed up for 4 years 78 children (51 boys, 27 girls) with mild (26%), moderate (48%), and severe (26%) AD (clinical score proposed by Rajka and Langeland). In all the patients IgE serum levels were checked and skin prick tests (SPTs) were performed at the first examination. The SPTs were repeated in 68 children at the end of the study. The children with severe AD had significantly higher IgE serum levels than those with mild or moderate AD. SPTs at the first observation were positive in 47% of cases, mostly in patients with severe AD, with a prevalence of food allergens, particularly in younger patients. At the second observation, SPTs were positive in 65% of cases, including 100% of children with severe AD. Inhalants were the most common allergens. An ARD appeared in 38% of all patients: in 75% of those with severe AD and in 54% of those with a positive first SPT. Allergic screening should be carried out at an early age, especially in severe AD, since SPT positivity to food allergens, associated with severe clinical AD symptoms and a high IgE serum level, identifies those children ages 0-3 years at high risk of development of ARD.

Immunological parameters in Darier's disease.

Patients with Darier's disease have frequently been observed to develop severe bacterial and viral infections. Previous studies have indicated some derangement in the immune system, even though no consistent or specific abnormality has yet been demonstrated. We performed the results of immunologic studies in 10 patients with Darier's disease. In each patient humoral immunity and cell-mediated immunity (in vivo and in vitro) were evaluated and leukocyte chemotactic function was assayed. Humoral immunity was normal; as regards clusters of differentiation (CD), a slight increase in CD4 lymphocyte subpopulations was observed in 7 patients and of CD4/CD8 ratio in 1 case. The lymphocyte responses to phytohemagglutinin and concanavalin A were normal, whereas the response to pokeweed mitogen was decreased slightly, but not significantly. Normal random and chemotactic mobility was found in all the patients except one. The data obtained do not show important immunological alterations. Our patients did not have a high propensity to develop severe infections and this may explain the absence of significant immunological derangement. Our data confirm that no immunological derangement is associated with Darier's disease.

Effect of house dust mite avoidance measures in children with atopic dermatitis.

BACKGROUND: House dust mite allergens are associated with atopic dermatitis (AD). OBJECTIVES: The aim of our study was to verify if house dust mite allergen avoidance measures can improve the clinical manifestations of AD in children. METHODS: Forty-one children (mean age 3.9 years) affected by AD associated with high total and/or specific IgE serum levels ('extrinsic' AD) were recruited. Clinical evaluation was performed utilizing the Severity Scoring of AD (SCORAD) index; dust was sampled from the children's beds and tested using an enzyme-linked immunosorbent assay. The study was planned in two parts. In the first part, a placebo-controlled trial of 2 months duration, mite allergen avoidance measures (encasing mattresses and pillows; a weekly hot wash of bedding; frequent vacuum cleaning of living room and bedroom; soft toys and carpets regularly cleaned or removed; no pets allowed) were recommended to group A patients, but not to group B. In the second part of the study, environmental avoidance measures were recommended to initial control group B patients also. One year after the start of the study the amounts of mite allergen in the home and clinical score of AD were measured in both groups. RESULTS: At the end of the first part of the study, significant decreases in major allergens of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) load (from 393 to 94 ng m-2) and concentration (from 1.84 to 0.73 microg g-1 of dust) in children's beds were observed in treatment group A. At the same time, in this group the mean SCORAD index improved significantly (from 33 to 26; P = 0.022). After 12 months, when all patients had used allergen avoidance measures, Der p1 + Der f1 load, concentration and clinical score had improved, reaching similar values in both groups. CONCLUSIONS: Simple mite allergen avoidance measures should be recommended to families with children affected by extrinsic AD in order to control the clinical manifestations and prevent mite sensitization.

Behçet syndrome: report of two early-onset cases treated with transfer factor.

Report of two cases of Behçet syndrome in children, one with the features of a neuro-Behçet syndrome and the other with chiefly severe ocular changes. Both children were treated with transfer factor when previous treatment had proved ineffective. Some years after the beginning of treatment, which is still continuing, transfer factor may be said to be of value in Behçet syndrome.

Mite allergen (Der p 1) levels in houses of children with atopic dermatitis: the relationship with allergometric tests.

Several studies, in particular in adult groups, have evaluated the involvement of mites in the pathogenesis of atopic dermatitis (AD). This still remains controversial. The objective of this study was to determine the level of house dust mites (HDMs) in the beds of a group of children with AD and correlate these levels with their allergometric assessment. Forty-one children with AD underwent allergometric tests (prick test, patch test and radioallergosorbent test, RAST) and the concentration levels of HDMs in their homes were evaluated. Our data show that about half of the children (51%) with AD presented Dermatophagoides pteronyssinus positivity (prick test and/or RAST and/or patch test). Dust was collected in the period October-November from the children's beds, by the same two operators, using a dust-collection device. The dust mite level was tested by an enzyme-linked immunosorbent assay with antibody against Der p 1 allergen. Ten children (24%) presented a Der p 1 concentration > 2 microgram/g of dust (the value assumed to be a risk level for sensitization), 20 (49%) between 0.1 and 2 microgram/g and 11 (27%) < 0.1 microgram/g of dust. In the group with the highest Der p 1 concentration (> 2 microgram/g dust) nine children (90%) presented an allergometric D. pteronyssinus sensitivity, the difference with the other two groups being statistically significant at P < 0.018. The results of the present study show that the highest HDM concentrations were observed in the group with an allergometric D. pteronyssinus positivity (prick test and/or RAST and/or patch test). It is hypothesized that a higher HDM concentration may elicit D. pteronyssinus IgE sensitization and delayed hypersensitivity in children with AD.

Serum immunoglobulins and lymphocyte subpopulations derangement in Turner's syndrome.

Abnormalities of the proportions of peripheral blood lymphocyte subpopulations and of immunoglobulin serum levels were found in twenty patients affected by Turner's syndrome. A slight but significantly decreased percentage of circulating T and B cells, and increased percentage of null cells and a decreased in vitro responsiveness of lymphocytes to phytohaemagglutinin, concanavalin A and pokeweed mitogen were found in Turner's syndrome patients. IgG serum level was found significantly decreased in comparison with age-matched fifty-seven normal males and fifty-seven normal females and IgM serum level was intermediate between female and male values; Turner's syndrome patients with monosomy had an IgM serum concentration very close to male values. The derangement of T and B lymphocyte subpopulations, probably related to the aneuploidy, does not seem to be a severe one but it could account for the immunoglobulin abnormalities and for the association of Turner's syndrome with immunological disorders such as autoimmune diseases. The role of X chromosome on IgM serum level is discussed.