ADMA, SDMA, L-Arginine and nitric oxide in allergic pediatric bronchial asthma.

Published data regarding asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine (L-ARG) and nitric oxide fraction in exhaled air (FeNO) in pediatric bronchial asthma are limited. Many question remain open about plasma concentration of these substances. The aim of this study is to evaluate ADMA, SDMA, L-ARG and FeNO concentration in allergic pediatric mild asthmatic patients in respect to healthy subjects. In this case-control study 60 children (50 asthmatics and 10 healthy) underwent a complete clinical visit, baseline respiratory function, allergy tests and biochemical analyses. The statistical significance of the different concentrations between the two groups were studied using one-way analysis of variance (ANOVA). A p value less than 0.05 was considered statistically significant. The mean plasma ADMA (0.58 vs 0.68 micromol/L), SDMA (0.40 vs 0.45 micromol/L) and L-ARG (52.2 vs 74.13 micromol/L) concentration were significantly lower (p less than 0.001) in the asthmatic patients in respect to healthy subjects (control group). The concentration of FeNO was significantly higher in the asthmatic subjects in respect to the control group (9.18 vs 4.2 micromol/L; p less than 0.001). Low plasma concentrations of ADMA, SDMA, L-ARG and high concentration of FeNO are associated with bronchial asthma and indicate an important role in airway disease through NO metabolism.

Pathogenesis and clinical approaches to anticonvulsant hypersensitivity syndrome: current state of knowledge.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but severe and potentially fatal, adverse reaction that occurs in patients who are treated with commonly used older anticonvulsant drugs (phenytoin, carbamazepine and phenobarbital) and/or with some newer agents (lamotrigine). Paediatric patients are at an increased risk for the development of AHS for the higher incidence of seizure disorder in the first decade of life. Hypersensitivity reactions range from simple maculopapular skin eruptions to a severe life-threatening disorder. AHS is typically associated with the development of skin rash, fever and internal organ dysfunctions. Recent evidence suggests that AHS is the result of a chemotoxic and immunologically-mediated injury, characterized by skin and mucosal bioactivation of antiepileptic drugs and by major histocompatibility complex-dependent clonal expansion of T cells. Early recognition of AHS and withdrawal of anticonvulsant therapy are essential for a successful outcome. In vivo and vitro tests can be helpful for the diagnosis that actually depends essentially on clinical recognition.

Sublingual immunotherapy in polysensitized patients: effect on quality of life.

BACKGROUND: Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients. OBJECTIVE: To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis. METHODS: We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer). RESULTS: The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P < .01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44. CONCLUSIONS: This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.

Sublingual immunotherapy in polysensitized allergic patients with rhinitis and/or asthma: allergist choices and treatment efficacy.

Polysensitization is very common in allergic patients and was previously reported to be associated with more severe symptoms and impaired quality of life. Polysensitization is often considered as a contraindication for specific immunotherapy (SIT). This study is aimed at evaluating the allergist attitude for decision making in choosing SIT in a cohort of Italian polysensitized patients. Moreover, the 1-year effectiveness of the prescribed sublingual immunotherapy (SLIT) in this cohort was evaluated. The study was performed on 244 patients (109 males, 135 females, mean age 28.7 years, S.D. 12.0) with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA criteria) treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, type of diagnosis, severity of symptoms, use of drugs, and adverse events were evaluated at baseline and after 1 year. A total of 230 patients were treated with SLIT: 165 with a single extract, and 65 with two different extracts (mix). SLIT treatment significantly improved disease staging, and reduced symptom severity and drug use. No systemic reaction was reported. In conclusion, these findings provide preliminary evidence that SIT is effective and safe in polysensitized patients after 1 year of treatment also using single extracts, and thus does not represent an obstacle for prescribing SIT.

Characteristics of patients with allergic polysensitization: the POLISMAIL study.

BACKGROUND: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients. METHODS: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated. RESULTS: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations. CONCLUSIONS: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Lack of correlation between clinical patterns of asthma and airway obstruction.

To evaluate the relationship between the classification of asthma and obstruction of airways, we have studied 100 children suffering from allergic asthma: 65 males and 35 females, aged 4.2-16.3 years (mean, 7.6 +/- 2.8 years), who were evaluated at least 1 month after the last attack of airway obstruction. We analyzed personal history of all children with special reference to number of attacks of airway obstruction in the last year, severity, and presence of respiratory symptoms in the last month. The children studied have been classified in three groups according to the International Pediatric Respiratory Allergy Forum (IPRAF) '98 method (Third International Pediatric Consensus Statement on the management of childhood asthma). All children underwent the assessment of their respiratory function by means of analysis of the flow/volume loops with measurement of the obstruction indices (forced expiratory volume in 1 second [FEV1], peak expiratory flow [PEF], and maximal midexpiratory flow [MMEF]). The efficacy of the aforementioned method has been evaluated by analyzing the number of the subjects who showed indices of airway obstruction not in agreement with the group assigned. Eighty-five of the children studied were diagnosed with infrequent episodic asthma (IEA), 14 children were diagnosed with frequent episodic asthma (FEA), and 1 child was diagnosed with persistent asthma (PA). Thirty-six of 100 children showed obstruction indices not in agreement with the asthma group: in particular, 24 of 85 children with IEA had FEV1 < 80%, 11 children with FEA had FEV1 > 80%, and 1 child with PA had FEV1 > 80%. The high percentage of discordance between clinical classification and obstruction index in the subjects with IEA can be caused by the persistence of abnormalities of the respiratory function without clinical symptoms. The presence of a normal obstruction index in the subjects with FEA can be explained by the pharmacologic therapies. These data suggest the usefulness of a careful evaluation of the respiratory function associated with a clinical assessment to carry out a more appropriate therapy.

Sensitization to environmental antigens in asthmatic children from a central Italian area.

This study was designed to evaluate the frequency of respiratory allergens in different age groups of asthmatic atopic children in the Chieti-Pescara area. We examined a pediatric population (507 children) aged between 1 to 17 years (mean 6.62 +/- 2.9). All the children were submitted to a panel of skin prick tests (SPT) for 12 common aeroallergens: Grass Pollens (G.), Parietaria (P.), Olive (O.), Artemisia (A.), Ragweed (R.), Dermatophagoides Pteronyssinus and Dermatophagoides Farinae (D.P. & D.F.), Cat and Dog dander (C.D.), Feathers (F.), Alternaria (Al.), Aspergillus (As.). All the subjects gave positive result to one or more allergens. The population was subdivided in to 4 groups according to their age (Group A: 1-3 years; Group B: 4-6 years; Group C: 7-9 years; Group D: 10-17 years). In each age group, we determined the number of subjects with 1, 2, 3, 4 or 5 and more than 5 positive SPT and the prevalence of positive SPT for different allergens. We found that 74% of 507 patients showed positive reaction to Dermatophagoides Pt, 71% to Dermatophagoides Fa, 45% to Grass, 23% to Parietaria, 21% to Olive, 17% to Artemisia, 17% to Cat's or Dog's danders, 13% to Alternaria, 5.9% to Ragweed, 5.9% to Feathers, and 4% to Aspergillus. In addition we detected that 12% of children examined were monosensitized; 56% were sensitized to 2 or 3 allergens; 22% were sensitized to 4 or 5 allergens, and then 8% were polysensitized to > 5 allergens. The allergy to grass pollens and to house dust mites was the most frequent in monosensitized. In the older patients, we found an increase in number of positives SPT to several allergens, and an increase in the frequency of Gr., P. and O. allergy, while the house dust mites sensitization remained constant in all groups and represented the dominant cause of asthmatic symptoms in this population. Our data confirm the importance of age in determining a respiratory polysensitization. In conclusion, our data suggest that house dust mites (D.P. and D.F.) and grass pollens are the most common allergens in asthmatic children of the Chieti-Pescara area.

Comparison of the Bronchodilator Effect of Inhaled Short- and Long-Acting beta(2)-Agonists in Children with Bronchial Asthma: A Randomised Trial.

OBJECTIVE: This study compared the bronchodilator effects of short-acting (salbutamol and procaterol) and long-acting (salmeterol and formoterol) beta(2)-agonists in children with bronchial asthma. PATIENTS: Twenty-seven (18 male, 9 female) children with bronchial asthma were enrolled in the study. Drugs were administered randomly in the morning for 5 days as follows: 1 single dose of two short-acting beta(2)-agonists, salbutamol 200microg and procaterol 20microg, and two long-acting beta(2)-agonists salmeterol 50microg and formoterol 24microg, and placebo. RESULTS: All beta(2)-agonists demonstrated a significantly higher bronchodilator effect than that observed with placebo. This effect appeared to be due to the forced expiratory flows. Formoterol produced a higher bronchodilator effect than salbutamol, and salmeterol showed a bronchodilator effect comparable with salbutamol at 30 minutes but higher than salbutamol after 3 hours. CONCLUSION: Our study confirmed the efficacy of the bronchodilator effects of the beta(2)-agonists. Salmeterol and formoterol, in particular, produced an improvement in respiratory function with a significant increase in forced expiratory flows in children with bronchial asthma.

Effectiveness of nedocromil sodium in preventing exercise-induced asthma in children.

Exercise-induced asthma is a well-known phenomenon, particularly affecting children, with an important social impact. In order to assess the usefulness of nedocromil sodium in the prevention of exercise-induced asthma, we studied 49 (15 females, 34 males) children who suffered from asthma; their mean +/- SD age was 9.2 +/- 3.0 (range: 3.3-19.1) years. On the first day respiratory function was evaluated by spirometry, basally and after 6 minutes. The inhalation of nedocromil sodium had a great influence on post-exercise lung function measurements; in fact on the day of nedocromil sodium pretreatment, our patients showed an increase of respiratory function, significantly different from the parameters recorded during the first day. Our findings suggest that nedocromil sodium is effective in the prevention of exercise-induced asthma, in pediatric age.

Pulmonary function in diabetic children with and without persistent microalbuminuria.

The principal spirometric and plethysmographic parameters were measured in 68 (38 female) diabetic children and adolescents, aged from 6.01 to 22.00 years; their duration of disease ranged from 1 to 247 months. Thirty-four patients had persistent microalbuminuria. The patients were studied basally and after the Bruce test. All the spirometric parameters were normal in all children, with and without microalbuminuria. The presence of microalbuminuria seems not to be a risk factor for the developing of abnormal pulmonary function.

Antiviral activity of nerve growth factor in vitro.

The antiviral activity of 'nerve growth factor' (NGF) on non-oncogenic DNA, on RNA viruses and on Moloney sarcoma retrovirus was evaluated in vitro. NGF was active against herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and Moloney sarcoma virus (MSV) at non toxic concentrations. The effects of different treatment regimens on HSV-1 infections indicate that the inhibitory action of NGF occurs at the early stages of viral replication. No activity was noted against coxsackie virus B1 (Cox B1), respiratory syncytial virus (RSV), Semliki forest virus (SFV), encephalomyocarditis (Columbia SK) and adenovirus of infectious canine hepatitis (ICH) at the highest concentrations tested.

Long-term therapy in childhood asthma: clinical and auxological effects.

The authors studied the effect of different therapeutical regimens on the growth of children suffering from asthma. These patients were subdivided into four groups of ten patients according to their therapeutic regimens: Group A = ketotifene (1 mg, two times/day), Group B = diproprionate beclomethasone + salbuthamol (100 + 200 mcg, 3 times/day), Group C = ketotifene + diproprionate beclomethasone, Group D = disodiumcromoglycate (20 mg, 3 times/day). The patients were followed for at least 1 year. Our study has shown that all the children treated with the four different regimens had a normal growth and growth velocity.

[Evaluation of nasal eosinophils after specific provocation in the diagnosis of respiratory allergy]. / La ricerca degli eosinofili nasali dopo provocazione specifica nella diagnosi di allergia respiratoria.

The authors describe the results of a study of a group of children suffering from allergic rhinitis; the Authors evaluated eosinophils, basally and after nasal provocation test. Both clinical and cellular responses were evaluated. The basal results were: presence of eosinophils in 9/17 (52.9%) subjects allergic to Graminacee, in 42/61 (68.3%) subjects allergic to Dermatophagoides and in 3/3 (100%) subjects allergic to Parietaria. The results of the clinical response are the following: Graminacee: positive response in 20/22 (90.9%) tests; Dermatophagoides: 48/63 (76.2%); Parietaria: 6/6 (100%). The results of laboratory response are the following: Graminacee: positive response in 14/18 (77.8%) tests; Dermatophagoides: 45/59 (76.3%); Parietaria: 5/5 (100%). The evaluation of both responses is useful to increase the sensitivity of the nasal provocation test.

IgG subclass deficiency and recurrent respiratory infections in children.

The aim of this study was to investigate the humoral immunity of children with recurrent respiratory tract infections. Fifty-seven (17 female, 40 male) children, aged from 1.1 to 12.0 years were evaluated, after 1 month from the last infectious disease. The total number of children with IgG subclasses deficiency was 29/57 with the following IgG deficiency distribution: IgG1 = 2 children, IgG2 = 13 children, IgG3 = 4 children, IgG4 = 25 children. Moreover, 13 children with IgG4 deficiency showed low levels of other (one or more) IgG subclasses. It is probable that these low IgG subclasses levels are an important immunological abnormality of these children.

Activity of FCE 20696, a new synthetic immunomodulator, in models of viral and bacterial pathology.

The dibenzopyran derivative FCE 20696 is an immunomodulator which protects mice infected with several viral agents and with Mycobacterium tuberculosis. The compound is able to decrease the severity of the lung lesions caused by influenza virus infection. Doses ranging from 12.5 to 100 mg/kg are effective even after a single administration. Activity is demonstrated by intraperitoneal, subcutaneous and oral administration of the drug. In systemic infection with herpes simplex virus type 1, the 100 mg/kg dosage, administered subcutaneously, is able to increase both the percentage and the mean survival time of mice. To have effect by oral administration it is necessary to give the compound twice in the day. Moreover, some activity has also been observed in mice infected by M. tuberculosis, when the compound is administered orally at doses of 1-2.5 mg/kg twice weekly for 5 weeks, during the course of the disease.

Adenosine deaminase inhibitors. Synthesis and biological activity of deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine.

Two new deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, 1), 7-deaza-EHNA (6) and 1,3-dideaza-EHNA (11), were synthesized and evaluated for adenosine deaminase (ADA) inhibitory activity and compared with EHNA, 1-deaza-EHNA (2), and 3-deaza-EHNA (3). Substitution of a methine group for a nitrogen atom in the 7-position of the purine moiety of EHNA produces a dramatic drop in the inhibitory activity (Ki = 4 X 10(-4) M) whereas compounds 2 and 3 are still good inhibitors (Ki = 1.2 X 10(-7) M and 6.3 X 10(-9) M respectively). EHNA and its deaza analogues so far synthesized were also tested in vitro for their antiviral and antitumor activity in a range of cellular systems. EHNA and 1-deaza-EHNA are equiactive as inhibitors of human respiratory syncytial virus (HRSV) replication (MIC = 6.25 micrograms/mL) while the other compounds are inactive. On the other hand, all the examined compounds displayed an antitumor activity comparable to that of the reference compound 1-beta-D-arabinofuranosyladenine (ara-A), 7-deaza-EHNA being the most active of all. The results obtained showed that there is no correlation between adenosine deaminase inhibition and antiviral or antitumor activity in this series of compounds. 3-Deaza-EHNA, the most active inhibitor of ADA among the EHNA deaza analogues, greatly potentiates the antitumor activity of ara-A in vitro. In vivo activity was observed only when the two compounds were used in combination.

Synthesis, DNA binding and antiviral activity of distamycin analogues containing different heterocyclic moieties.

A series of novel distamycin analogues possessing an additional benzene or heterocyclic ring have been synthesised and tested for selective DNA binding properties and antiviral activity. Inhibition of herpes virus in cell culture appears to be related to AT base pair specificity. Some of the new compounds are also more potent than the parent distamycin against Moloney sarcoma virus.

[Chernobyl accident: dosimetric evaluation and estimation of risks]. / Incidente di Chernobyl. Valutazioni dosimetriche e stime dei rischi.

The results of dosimetric evaluations carried out after Chernobyl accident in the Health Physics Department of Niguarda Ca' Granda Hospital (Milan) on air, rain and ground contamination are presented. The results obtained show that the incidence of stochastic late effects, both somatic and genetic, will be so low that practically will not be distinguishable from "natural" incidence.