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.

Genetic epistasis between killer immunoglobulin-like receptors and human leukocyte antigens in Kawasaki disease susceptibility.

Kawasaki disease (KD) is a pediatric acute multisystemic vasculitis complicated by development of coronary artery lesions. The breakthrough theory on KD etiopathogenesis points to pathogens/environmental factors triggered by northeastern wind coming from China. Natural Killer cells and T lymphocytes express the inhibitory/activating Killer Immunoglobulin-like Receptors (KIR) to elicit an immune response against pathogens by binding to human leukocyte antigens (HLA) class I epitopes. We first report on the role of KIR/HLA genetic epistasis in a sample of 100 Italian KD children. We genotyped KIR, HLA-A, HLA-B and HLA-C polymorphisms, and compared KD data with those from 270 Italian healthy donors. The HLA-A*11 ligand for KIR2DS2/2DS4/3DL2 was a KD susceptibility marker by itself (odds ratio (OR)=3.85, confidence interval (CI)=1.55-9.53, P=0.004). Although no epistasis between HLA-A*11 and KIR2DS2/S4 emerged, HLA-A*11 also engages KIR3DL2, a framework gene encoding for a pathogen sensor of CpG-oligodeoxynucleotides (CpG-ODN), and KD blood mononuclear cells are actually prone to pathogen CpG-ODN activation in the acute phase. Moreover, carriers of KIR2DS2/HLA-C1 and KIR2DL2/HLA-C1 were more frequent among KD, in keeping with data demonstrating the involvement of these HLA/KIR couples in autoimmune endothelial damage. The highest KD risk factor was observed among carriers of KIR2DL2 and two or more HLA ligands (OR=10.24, CI=1.87-56.28; P=0.007).

Pulmonary and sinus diseases in primary humoral immunodeficiencies with chronic productive cough.

AIMS: To prospectively evaluate sinopulmonary disease in 24 patients with primary humoral immunodeficiency (11 with agammaglobulinaemia, nine with isolated IgA deficiency, and two with common variable immunodeficiency) and chronic productive cough, ascertain the usefulness of chest high resolution computed tomography (HRCT) in evaluating the progression of lung disease, and test a therapeutic approach to chronic sinusitis. METHODS: Pulmonary abnormalities were evaluated using lung function tests and HRCT (Bhalla score); chronic sinusitis was diagnosed clinically and confirmed by flexible fibreoptic endoscopy. Sixteen patients entered the three year follow up. RESULTS: Lung function testing revealed an obstruction in four patients; chest HRCT was abnormal in 16. There was a linear relation between the Bhalla score > or =4 and the number of months with cough/year over the previous two years (clinical score), and between the difference in clinical scores during follow up and in the previous two years and the difference in Bhalla score. The pulmonary lesions did not significantly progress over a three year period. Thirteen patients had chronic sinusitis; 6/10 patients followed up were successfully treated with antibiotics plus topical therapy and two with nasal polypoid disease with endoscopic sinus surgery. CONCLUSIONS: In patients with primary humoral immunodeficiency and chronic productive cough, HRCT is very useful in delineating the extent of lung damage. The correlation between Bhalla score and clinical findings and the favourable outcome of the disease suggests that in most patients chest HRCT should not be repeated annually as previously suggested. Medical therapy seems to be effective in many cases of chronic sinusitis.

[Current developments in the use of intravenous immunoglobulins]. / Attualità in tema di immunoglobuline per uso endovenoso.

The use of intravenous immunoglobulins (IVIG) has provided a substantial therapeutic advance in the treatment of antibody deficiency syndromes improving the quality of life of the affected patients. Among the advantages there are the possibility to employ higher doses to reach higher serum levels, with a more efficacious prophylaxis against infections; the prevention of chronic lung disease if IVIG are prescribed early, at diagnosis or at least at the onset of symptoms; the significant improvement of pulmonary function. The IVIG which are likely to be the best choice are the "intact Fc" preparations. In these products, or at least in some preparations, all IgG subclasses are present, which are endowed with specific and differentiated functions. Another important requirement is the presence of specific antibodies (e.g. anti Mycoplasmas, anti Campylobacter, anti Echovirus, anti pyogenic bacteria). The benefits of the prophylactic use of IVIG in preterm and low birthweight infants to prevent neonatal and late-onset infections are widely accepted. Lastly, IVIG are employed successfully in some autoimmune diseases as PTI and immune cytopenias, myasthenia gravis, acute and chronic inflammatory demyelinating polyneuropathy, Kawasaki syndrome, childhood recurrent seizures, juvenile chronic arthritis.

[Evaluation of the efficacy and tolerance of ceftriaxone in childhood]. / Valutazione dell'efficacia e tollerabilità del ceftriaxone in pediatria.

Between the years 1981 and 1983 we treated with Ceftriaxone (Cx) 34 children--aged 15 days to 13 years--affected with serious infections: 18 infections of lower respiratory tract, 1 sepsis caused by E. Coli, 1 meningitis with cloudy cerebrospinal fluid, 1 submandibular adenitis with otitis, 1 otitis, 12 infections of the urinary tract caused by Proteus mirabilis, E. Coli, Klebsiella oxitocica and Klebsiella pneumoniae. Whenever bacteria were isolated by cultures, sensibility in vitro to Cx was tested. Cx was given i.m. or i.v. at a dose ranging from 50 to 135 mg/Kg/die according to the age and the seriousness of the infections; in 17 children Cx was administered once daily, in the other patients in two divided doses. The following laboratory measurements were obtained before, during and after treatment: complete blood cell count, platelet count, total bilirubin, creatinine, SGOT, SGPT, alkaline phosphatase and urinalysis. Patients were also monitored daily for clinical signs and symptoms such as fever, general conditions, heart rate, respiratory rate, blood pressure. Twenty children showed a good clinical response (1 sepsis, 1 otitis, 1 adenitis, 1 meningitis, 12 infections of the urinary tract, 4 infections of the lower respiratory tract); urine sterilization was achieved after three days of therapy in all patients with infections of the urinary tract. Remarkable clinical and radiological improvement in 9 patients with infections of lower respiratory tract was observed while in only 4 children with bronchopneumonia therapy was ineffective although the dosage of Cx was adeguate; in these patients a further antibiotic treatment was necessary for a complete recovery.(ABSTRACT TRUNCATED AT 250 WORDS)