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Biomedical subjects

M Bardare

Publications and source records attributed to M Bardare.

At least 19 recordsLinked to original sources

Evidence of clonotypic pattern of T-cell repertoire in synovial fluid of children with juvenile rheumatoid arthritis at the onset of the disease.

Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are characterized by chronic inflammation, synovial cell proliferation and progressive joint damage. It has been speculated that T cells play an important role in the pathogenesis of RA and JRA in the early stage of the disease. Previous studies have demonstrated discrepant results regarding the significance of T-cell clonality in RA or JRA lesions. It can be postulated that the heterogeneity of these data may be linked to the stage of the disease, as the relative importance of selective immunological events is different during the time from onset to established disease. To avoid this problem, we conducted the present study in nine children affected by JRA at the onset of the disease and before treatment. We analysed the T-cell receptor beta chain variable (TCRBV) of CD4+ and CD8+ lymphocytes in peripheral blood (PBL) and synovial fluid (SFL), by a panel of monoclonal antibodies (MoAbs). Furthermore, to assess the clonotypic pattern of T-cell repertoire, the CDR3 length distribution was evaluated by spectratyping analysis. Our results showed no significant expansion of distinct TCRBV subset in either synovial or peripheral compartments. Conversely, when we studied the CDR3 length distribution, an oligoclonal pattern was found in the SFL of six patients, suggesting the presence of a clonotypic restriction of T cells in SFL, which is not detectable in PBL. These findings are consistent with an antigen driven T-cell expansion sequestered at the inflammatory site.

Antibodies, Monoclonal↗

Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children: a prospective multicenter study.

OBJECTIVE: Osteopenia/osteoporosis is being increasingly reported as a complication of many chronic diseases, even in children. In this preliminary study, we evaluated the effect of an oral bisphosphonate (alendronate) on bone mass in children with diffuse connective tissue diseases. METHODS: Thirty-eight children with low bone mass were treated with alendronate for 1 year; 38 children who had the same primary disorders as the study patients but in a less severe form served as untreated control patients. We were also able to evaluate changes in bone mass (before and after alendronate) in 16 of the treated patients whose bone mineral density (BMD) had been routinely measured before the present study was initiated. RESULTS: BMD increased by a mean +/- SD of 14.9 +/- 9.8% (P < 0.002 versus baseline) in the treated patients (reaching the normal range in 13 patients), while the BMD was 2.6 +/- 5% (not significant versus baseline) in the control group (15 had a decrease). Most interestingly, there was a large increase in BMD (15.3 +/-9.9%) after alendronate therapy in the 16 children who had their BMD followed up in the year before the study, during which time they had shown little increase in BMD (1.03 +/- 6.3%), and often a decrease. Considering their condition, increases in the height of all patients was satisfactory. No new fractures were observed after alendronate therapy was initiated. CONCLUSION: Bisphosphonates can be considered essential components of the treatment of secondary osteoporosis, not only in adults, but also in pediatric patients. Alendronate has a positive effect on secondary osteopenia/osteoporosis in children with connective tissue diseases.

Adolescent↗

Bone mass change during methotrexate treatment in patients with juvenile rheumatoid arthritis.

Thirty-two children affected by juvenile rheumatoid arthritis (JRA) were studied with serial measurements of bone mass for an average of 18 months, to evaluate the effects of long-term methotrexate (MTX) treatment on bone. Bone mineral density (BMD) was measured on lumbar spine and total body. During MTX therapy some increase in BMD was observed, though this was smaller than in a control group of healthy children. Axial (spine and trunk) and appendicular (upper and lower limbs) BMD showed similar increases. BMD, either as an absolute value or as a percent variation from baseline, did not correlate with either MTX dose or length of therapy. In children treated also with corticosteroids, these drugs negatively influenced bone mass increase. The main determinant of absolute spine BMD value appeared to be weight, while height and lean mass seemed to be the determinants of total body BMD. Pubertal stage and disease activity significantly influenced the yearly change in BMD. In conclusion, our data suggest that long-term, low-dose therapy with MTX does not induce osteopenia in children with JRA.

Adolescent↗

Responsiveness of outcome measures in juvenile chronic arthritis. Italian Pediatric Rheumatology Study Group.

OBJECTIVE: To examine the responsiveness of the disease activity measures more commonly used in juvenile chronic arthritis (JCA) clinical trials. METHODS: Data were obtained from an open-label, non-controlled, multicentre trial designed to investigate the efficacy of methotrexate (MTX) in children with JCA. Outcome measures, including physician and parent global assessments, functional ability measures, articular variables, and laboratory indicators of systemic inflammation, were assessed at baseline and after 6 months of MTX treatment in 132 patients. Responsiveness of endpoint variables was evaluated by assessing the effect size (ES) and the standardized response median (SRM). RESULTS: Physician and parent global assessments were the more responsive instruments, showing ES and SRM above 1.0. Erythrocyte sedimentation rate, C-reactive protein, functional status measures and articular variables showed intermediate responsiveness. Morning stiffness, haemoglobin and platelet count were the least responsive instruments. CONCLUSION: The results of our analysis indicate that subjective estimations of the disease activity, either by the physician or parents, are the most responsive instruments in the assessment of the therapeutic response in children with JCA. The responsiveness of outcome measures in JCA should be further investigated in prospective controlled studies.

Adolescent↗

Arthritis as a presenting feature of non-Hodgkin's lymphoma.

Leukaemia can present with joint swelling in the absence of abnormal haematological findings. Arthritis as a presenting sign of lymphoma, however, is extremely rare. Three children with non-Hodgkin's lymphoma who had joint swelling at the onset of their disease are reported. Two cases showed histological features of anaplastic large cell lymphoma (Ki-1/CD30 positive), and one of angioimmunoblastic T cell lymphoma. In all patients the unusual presentation delayed correct diagnosis.

Arthritis↗

Idiopathic limb edema in children with chronic arthritis: a multicenter report of 12 cases.

Lymphedema, a well known extraarticular manifestation of rheumatoid arthritis, has been rarely described in children with idiopathic chronic arthritis. We describe 12 cases of lymphedema and idiopathic arthritis of childhood seen at 4 different pediatric rheumatology centers. Eight patients were girls, 4 boys; the age at appearance of lymphedema ranged from 2.3 to 17 years. In all patients except one, lymphedema was localized to the lower limbs. The outcome of lymphedema was variable, but not always related to the arthritis course, and was mostly independent of any specific therapy. Lymphography was performed in only one patient, and revealed lack of lymphatic drainage in the affected leg. We conclude that the association of lymphedema and idiopathic arthritis of childhood is not rare; this association is unlikely to be coincidental, even though the pathogenetic mechanisms are currently not well understood.

Adolescent↗

Soy allergy in atopic children.

BACKGROUND: Although soy is considered a major food allergen (along with milk, egg, peanut, fish, and wheat), the prevalence of soy allergy in the pediatric population is not well defined. OBJECTIVE: To determine the prevalence of soy allergy in atopic children attending the Allergy Clinic at the Pediatric Department of Milan University. METHODS: Seven hundred four patients with allergic signs and symptoms, aged 1 month to 18 years, were recruited between December, 1991 and April, 1992. The subjects with positive skin prick tests to soy were tested using a DBPCFC with powdered soy formula in fruit juice, and rice or corn flour as placebo. In children who refused the liquid challenge, capsules containing dehydrated soy flour or talcum powder as placebo were administered. An age-matched and sex-matched group of subjects with negative skin prick tests to soy were tested using an open challenge with soy formula. RESULTS: A positive skin prick test to soy was found in 148/704 patients (21%); 131 out of 148 children with positive skin prick test (group A) and 131 out of 556 children with negative skin prick test to soy (group B) were challenged with soy: 8/131 (6%) in group A had a positive soy challenge while no clinical reactions were observed in children in group B. A younger median age, a positive past and current personal history of cow milk allergy, and a previous history of soy allergy were found most often in children with positive soy skin prick test and positive soy challenge than in children with positive skin prick test and negative soy challenge. The eight soy-allergic children reacted to the soy challenge mostly with cutaneous and gastrointestinal symptoms; symptoms were immediate in six and late in two children. The eliciting dose of soy was very small in the immediate reaction; higher and repeated doses were necessary for the onset of late reactions. CONCLUSION: The prevalence of clinical soy allergy in our children with positive skin prick tests to soy is 6.1% (8/131), while none of 131 children with negative skin prick test to soy reacted to the challenge.

Child↗

A three-year double-blind placebo-controlled study with specific oral immunotherapy to Dermatophagoides: evidence of safety and efficacy in paediatric patients.

Very few double-blind trials of oral immunotherapy have been reported. The majority of these have been performed with pollen extracts and the results have often been equivocal. The major weaknesses of these studies have been the short periods of the trials, the low doses of allergen employed and inadequate evaluation of efficacy. The present study has involved a placebo-controlled double-blind trial of oral immunotherapy for three years with Dermatophagoides pteronyssinus at relatively high doses in 18 paediatric patients. Throughout the trial clinical parameters (symptom and medication scores) and immunological parameters (specific IgE, IgG1 and IgG4 levels) were monitored in order to assess the safety and efficacy of the treatment. The treatment was well tolerated by all patients and no side-effects were experienced. Clinical improvement was evident after the second year of therapy and this was confirmed by a significant reduction in conjunctival reactivity assessed by a specific conjunctival provocation test. In addition, there were significant changes in the immunological parameters with a reduction in specific IgE and increased levels of IgG4 and IgG1, results in keeping with previous studies of oral and subcutaneous immunotherapy. Although the results do not provide an explanation of the basis of successful oral immunotherapy, they clearly demonstrate the efficacy and safety of the treatment and suggest that it may be a useful and more acceptable alternative for patients than the traditional subcutaneous immunotherapy.

Administration, Oral↗

Levels of circulating intercellular adhesion molecule 1 and E-selectin in serum and synovial fluid of juvenile chronic arthritis patients.

OBJECTIVE: To measure the levels of two adhesion molecules (AM), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin), in serum and synovial fluid (SF) of patients with juvenile chronic arthritis (JCA). METHODS: Both soluble AM levels were tested, in serum and synovial fluid (SF) samples, with an enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Serum levels of sICAM-1 and sE-selectin in JCA patients were not significantly different from those of a control group. Synovial fluid levels of sICAM-1, but not of sE-selectin, assayed significantly higher (p < 0.05) in JCA patients than in controls. Moreover SF levels of both molecules correlated negatively with disease duration, being higher in the earliest phases. No significant correlations were found between JCA sICAM-1 and sE-selectin levels and leukocyte count or ESR. CONCLUSIONS: These observations may signify a more important role of ICAM-1 than E-selectin in the migration of inflammatory cells into JCA SF. The negative correlation of both AMSF levels in JCA patients with disease duration could reflect a higher expression of ICAM-1 and E-selectin during the earliest phases of the disease.

Adolescent↗

Double blind, placebo controlled study of nedocromil sodium in asthma.

After a two week baseline, 209 asthmatic children (mean age 10 years, range 6-17) were randomly allocated to receive 4 mg nedocromil sodium (n = 110) or placebo (n = 99) four times daily for 12 weeks in addition to their current treatment. The children completed daily diary cards and visited the clinic at four week intervals. Statistically significant differences in favour of nedocromil sodium were seen for clinician assessment of asthma severity and diary card symptom scores, pulmonary function and inhaled beta 2 bronchodilator use. Total symptom score decreased by 50% from baseline in the nedocromil sodium group and by 9% in the placebo group during the final four weeks. Nedocromil sodium was considered very or moderately effective by 78% of children/parents (placebo 59%) and 73% of clinicians (placebo 50%). Nausea, headache and sleepiness, and dyspnoea led to withdrawal of one child from nedocromil sodium and placebo treatments, respectively. Reports of sore throat and headache were marginally greater with the nedocromil sodium treatment. It is concluded that nedocromil sodium was both effective and safe in the treatment of asthma in children.

Adolescent↗

[The use of thymopentin in the prevention of recurrent infections of the respiratory system. Multicenter study].

Eighty children, between 1-12 years, suffering from recurrent respiratory infections were admitted to a multicentre study and treated with thymopentin, an immunomodulating compound that represents the active site of the natural thymic hormone thymopoietin. Thymopentin efficacy, measured as reduction in the number of infective episodes, and tolerability were assessed and, at the end of the study a global evaluation was made by each investigator. Moreover, the following factors were recorded: clinical course, duration of symptoms/signs, frequency of administration of antipyretic, antibiotic, anti-inflammatory and mucolytic therapy, school attendance and hospitalization. Thymopentin treatment resulted in a statistically significant decrease of infective recurrences. The use of symptomatic and antibiotic drugs was also reduced. Side effects were few and mild. The investigators' overall evaluation of thymopentin's efficacy and tolerability was favourable. In conclusion, thymopentin, administered subcutaneous for 5 weeks in winter, may be useful in the treatment of children with recurrent infections of the respiratory tract.

Child↗

Influence of dietary manipulation on incidence of atopic disease in infants at risk.

Of 5,500 newborn infants whose family histories were screened, 900 were found to have anamnestic risk. Cord-blood IgE was evaluable in 4,677 of these newborns, of which 394 had levels > or = 1 IU/mL; 84 infants had both anamnestic risk and elevated cord-blood IgE levels. Parents of infants with anamnestic risk were informed of their child's risk of atopy. Additionally, for 391 infants at two of the three participating hospitals, a preventive diet was prescribed that recommended breastfeeding for the first 6 months of life, with maternal diet restricted to no more than 200 dL of cow milk per day, no more than one egg per week, and no tomato, fish, shellfish, nuts, or foods allergenic to the mother. Only soy formula was recommended, and introduction of solid foods was also carefully prescribed. Furthermore, doctors recommended against exposure to tobacco smoke, animal allergens, and early entrance into daycare. Evaluable infants whose parents complied with the prescribed diet were found to have a lower incidence of atopy during the first year of life (13.3%, n = 158) than infants whose parents had ignored the prescribed diet (54.7%, n = 86) or infants whose parents were offered no dietary recommendations (28.9%, n = 218). Differences between the compliant group and the two groups with unrestricted diets were significant, indicating that this prescribed diet may protect against or delay onset of food allergies during the first year of life.

Female↗

Antibody response to inactivated polio vaccine (E-IPV) in children born to HIV positive mothers.

In order to evaluate the response to immunization of HIV-infected children we studied the humoral response to an enhanced potency inactivated poliovaccine (E-IPV) of 43 children born of HIV seropositive mothers. All these subjects have been followed for 32 (15-48) months in order to ascertain their infection status. After a course of 2 doses of E-IPV, 88% of children had neutralizing antibody (n.a.) titers greater than 1:4 to the 3 poliovirus serotypes and 100% to at least 2 polio strains. No statistically significant differences both as rates of n.a. positive subjects and as antibody levels were found between HIV infected children and those who lost HIV antibodies. The poorest response was observed in subjects with full-blown immunodeficiency (CD4 less than 1000/mm3, reduced response to PWM). Sixteen children also received a booster dose of vaccine one year after the completion of the primary cycle. Infected and non-infected subjects responded to the same extent with high levels of n.a. to this immunization. Interestingly, the recall dose was also able to induce high n.a. titers in those HIV infected children who showed significant decreases of n.a. titers in the months following the end of the primary cycle.

Antibodies, Viral↗

[Therapy of juvenile rheumatoid arthritis].

The correct drug treatment of JRA must consider the course and the subtype of the disease. Nonsteroidal antiinflammatory drugs are the first choice treatment, especially the recent ones which are more active and less toxic. The slow-acting antirheumatic drugs are the second choice treatment and must be employed in the chronically active stages of the disease; good results have been obtained with sulphasalazine and methotrexate both on clinical features and on blood biochemistry with relatively scarce side effects. Thymic hormones, cyclosporin A and intravenous immunoglobulins, though not yet widely experienced, can represent a worthwhile alternative to standard treatment in carefully selected cases. Steroids must be used only in special cases (particularly aggressive systemic JRA, carditis, severe anemia and those patients who fail to respond to usual treatments) and must be withdrawn as soon as possible to avoid adverse effects and steroid-addiction. Intraarticular long-acting steroids are the first choice treatment for rheumatoid monoarthritis.

Adolescent↗

[Local immunotherapy prevention of recurrent respiratory infections in children].

A group of 20 children aged between 2.5 and 10 years with recurrent respiratory infections (greater than 6/year) was treated with local immunotherapy (Biomunil spray) for a six-month period (October-March 1988/89). Referring to the same period on last year, a statistically significant decrease of upper respiratory infections was observed (p less than 0.001) as well as an increase of S-IgA rate (p less than 0.001) and less of serum IgA and IgG. The compliance and the tolerance of the drug was good.

Adjuvants, Immunologic↗