Modulation of gut microbiota downregulates the development of food allergy in infancy

In humans, microbial colonisation of the intestine begins just after birth. However, development of the normal flora is a gradual process, which is initially determined by factors such as genetic aspects, the maternal-foetal interaction, place and mode of delivery, early feedings strategies, and the use of antibiotics. Current knowledge on the significance and impact of the gut microflora on the development of the gut immune system indicates that a close relationship between allergic sensitisation and the development of the intestinal microflora may occur in infancy. Intestinal micro-organisms could downregulate the allergic inflammation by counterbalancing type 2 T-helper cell responses and by enhancing allergen exclusion through an immunological response

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Modulation of gut microbiota downregulates the development of food allergy in infancy.

In humans, microbial colonisation of the intestine begins just after birth. However, development of the normal flora is a gradual process, which is initially determined by factors such as genetic aspects, the maternal-foetal interaction, place and mode of delivery, early feedings strategies, and the use of antibiotics. Current knowledge on the significance and impact of the gut microflora on the development of the gut immune system indicates that a close relationship between allergic sensitisation and the development of the intestinal microflora may occur in infancy. Intestinal micro-organisms could downregulate the allergic inflammation by counterbalancing type 2 T-helper cell responses and by enhancing allergen exclusion through an immunological response.

Shaken baby syndrome: intending to harm or attempting to help?

PURPOSE: To describe the role of ophthalmologists in shaken baby syndrome evaluation. METHODS: Case report. RESULTS: A 3.5-month-old girl was admitted to the Pediatrics Clinic with lethargy. The mother, who brought in the baby, claimed that the baby had fallen from her cradle 6 hours ago. Clinical examination showed signs of head injury. Ophthalmologic examination was requested and revealed extensive retinal hemorrhages bilaterally covering the whole fundus, and retrohyaloid hematoma in the right eye. Computerized tomography neuroimaging documented large subdural hematomas exerting force on the brain parenchyma. The sum of the results of the clinical and neuroimaging examination-retinal hemorrhages and subdural hematomas-was indicative of violent shaking of the baby. Coronal evaluation was unable to determine whether the baby was abused by her parents or whether she was accidentally hurt. CONCLUSIONS: Ophthalmologic examination is necessary to document shaken baby syndrome since it reveals the retinal hemorrhages which together with the neuroimaging findings are almost always present in such cases. However, even when all the signs of shaken baby syndrome are present, it is difficult and sometimes destructive for a parent to be falsely accused of abusing his or her own child.

Biochemical markers of bone metabolism in infants and children under intravenous corticosteroid therapy.

The short-term effects of corticosteroids (CS) administered intravenously (IV) on biochemical parameters of bone metabolism were followed in infants and children. Forty-nine patients from 2 months to 10 years of age, admitted to Pediatrics Department for bronchiolitis, viral-associated wheezing and croup, were treated with IV hydrocortisone or methylprednisolone (10 or 2 mg/Kg/day, respectively) for 3 days. Blood and fasting urine were collected on admission (day 1), 2 days later (day 3) and 12 days after the end of therapy (day 15). Fifty-one children of similar age and gender without respiratory problems or bone diseases were used as controls. On day 3, suppression of the bone formation markers osteocalcin (OC) (P < 0.001) and total alkaline phosphatase (ALP) (P < 0.05) was observed, but not of the bone resorption markers of hydroxyproline, pyridinoline and calcium excretion (UHyp/UCr, UPYD/UCr and UDPD/UCr, UCa/UCr). Significant decreases were indicated in serum phosphate (Pi) and the maximum renal tubular Pi reabsorption (TmP/GFR) compared to basal (P < 0.001). No significant changes were noticed in the circulating levels of calcium (Ca), parathyroid hormone (iPTH), 25OHD, 24,25(OH)2D, 1,25(OH)2D, the insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3). Two weeks after therapy, the increase of OC to higher than basal (P < 0.01) indicated a probable activation of the osteoblasts. Serum Pi and the TmP/GFR index values that had significantly decreased by day 3 returned to pretreatment levels by day 15. When assessing the effects of the CS in relation to age, no changes were detected in the levels of OC and total ALP in the <12-month-old children, but a fall of OC was observed in the >1-year-old group (P < 0.001). In contrast to the OC, the effects on serum and renal tubular reabsorption of phosphate were similar for both groups. In conclusion, short-term IV administered CS led to significant but reversible inhibition of bone formation markers, especially detectable in the >1-year-old children, without affecting the bone resorption ones. The adverse effects on phosphate metabolism were also significant, but temporal and irrespective of age.

Distensibility and pulse wave velocity of the thoracic aorta in patients with juvenile idiopathic arthritis: an MRI study.

OBJECTIVE: An increased incidence of cardiovascular disease has been found in rheumatic disorders. Changes in the variables of aortic elasticity in patients with juvenile idiopathic arthritis (JIA) were evaluated and their relationship to inflammation, anti-rheumatic drugs and traditional cardiovascular risk factors were investigated in this study. METHODS: Phase contrast MR was performed in 31 patients with JIA and 28 age and sex matched controls to evaluate the aortic distensibility and pulse wave velocity (PWV). Disease activity variables, plasma lipid profile, homocysteine, thyroid hormones, glucose and insulin were assessed in the patients. RESULTS: Eighteen patients had oligoarticular, 6 polyarticular and 7 systemic disease. Distensibility was lower (mean: 10.25; SD: 4.18) and PWV was higher (mean: 3.68; SD: 1.59) in the patients compared to the controls (mean: 13.4; SD: 4.99), (mean: 1.38; SD: 0.54) respectively (p < 0.01). A positive correlation between PWV and age was observed in the patients (rs = 0.47, p < 0.01) and controls (rs = 0.72, p < 0.01), and a negative correlation between distensibility and age in the patients (rs = -0.59, p < 0.01) and controls (rs = -0.63, p < 0.01). No statistically significant correlations were found between distensibility and PWV and metabolic and disease activity parameters. When distensibility and PWV were adjusted for age no significant differences were found between the three subtypes of JIA. CONCLUSION: JIA is associated with increased aortic stiffness that might suggest subclinical atherosclerosis. Early detection and follow-up by non-invasive methods may be useful in the prevention of future cardiovascular disease.

The role of MRI in the evaluation of hip joint disease in clinical subtypes of juvenile idiopathic arthritis.

The purpose of this study was to evaluate the role of MRI in the assessment of hip joint involvement in clinical subtypes of juvenile idiopathic arthritis (JIA). 28 patients (mean age 12.5 years) with JIA (oligoarthritis 8, polyarthritis 13, systemic arthritis 7) were examined with T(2) weighted turbo spin echo and T(1) weighted spin echo (plain and contrast enhanced) sequences. The severity of joint involvement was evaluated using an MR grading score: grade 1=no contrast enhancement; grade 2=focal synovial contrast enhancement; grade 3=diffuse synovial contrast enhancement; grade 4=grade 3+diffuse synovial thickening; grade 5=grade 4+villonodular synovial thickening; and grade 6=grade 5+cartilage and subchondral bone erosions. MRI was abnormal in 57.1% of cases (25% of oligoarthritis, 53.8% of polyarthritis and 100% of systemic arthritis). Clinical examination was positive in 32.1% of cases and was associated with higher MR grades (mean 4.6, SD 1.34) compared with a negative clinical examination, which was associated with lower MR grades (mean 1.78, SD 1.13) (p<0.001). Patients with active disease (mean grade 3.9, SD 2) had higher MR grades than those with inactive disease (mean grade 2.1, SD 1.4) (p<0.01). The MR grades were different in the three clinical subtypes: oligoarticular (mean 1.5, SD 1.06); polyarticular (mean 2.38, SD 1.55); and systemic (mean 4.85, SD 1.21) (F:12.3, p<0.001), with a significant difference between systemic arthritis and oligoarthritis, and between systemic arthritis and polyarthritis (p<0.001). MRI of the hip might be considered for inclusion in the study protocol of patients with JIA since it reveals joint involvement at early stages and provides a detailed evaluation of the extent of joint disease.

Effects of intranasal salmon calcitonin in juvenile idiopathic arthritis: an observational study.

The aim of this study was to follow the changes in bone mineral density (BMD) and biochemical markers of bone turnover in 10 children (7.5-17.5 years of age) with severe juvenile idiopathic arthritis (JIA), during a 3-year therapy with salmon calcitonin (100 IU/day 2 months on and 2 off for a year and 200 IU/day for 2 years) and calcium (500 mg/day). All patients were functional classes III and IV and were measured at yearly intervals with a dual photon absorptiometer at the lumbar spine. The changes observed were 7.2-9.5% per year for BMD and 2.0-6.0% for volumetric bone mineral density (BMDvol). The bone resorption markers showed significant decreases after a year's treatment (Pyr/Cr from 175+/-15 to 108+/-15 nm/mm, P < 0.001, Pyr-D/Cr from 24.3+/-3.5 to 13.3+/-1.9 nm/mm, P < 0.05, and OHPr/Cr from 57.4+/-11 to 35.1+/-8.4 microg/mg) and smaller changes thereafter. No significant changes were observed in the bone formation markers of osteocalcin and alkaline phosphatase. Serum iPTH, the vitamin D metabolites, and calcium concentrations fluctuated within normal, while calcium excretion increased from 0.3+/-0.1 to 1.9+/-0.4 mg/kg/24 hours, P < 0.001. In conclusion, the present study, despite its limitations of not being placebo controlled, shows possible beneficial effects of intranasal calcitonin on bone resorption and pain relief in JIA patients.

Streptococcus mitis septicaemia and hepatitis.

The case of an otherwise well 9-y-old boy with fever, papular rash, jaundice and impaired liver function is presented. Streptococcus mitis sensitive to penicillin grew in blood culture. The boy had an excellent outcome. The clinical spectrum of viridans streptococci may be wider than currently anticipated, and Streptococcus mitis may cause septicaemia and hepatitis in immunocompetent individuals.

Nationwide collaborative study of HLA class II associations with distinct types of juvenile chronic arthritis (JCA) in Greece.

The aim of this study was to investigate the association of different groups and subgroups of juvenile chronic arthritis (JCA) with HLA class II (DR, DP, DQ) alleles and/or haplotypes. Groups and subgroups were mainly distinguished on the basis of the type of onset, the course and complications of the disease, and some predefined disease markers according to the criteria proposed by the ILAR Standing Committee (Chile, 1994). On the basis of these criteria the following five JCA groups and their subgroups were included in the study: (1) define systemic onset (n = 25) and systemic progressing to persistent arthritis (n = 14); (2) JCA of oligoarthritis onset (O-JCA, n = 124) and of oligoarthritis onset and course (n = 98), O-JCA of early (< 6 years) or late (> 6 years) onset (EOO-JCA n = 71 and LOO-JCA n = 44), O-JCA with ANA positive (n = 69) or negative (n = 55) and O-JCA progressing to extended arthritis (n = 22); (3) JCA of polyarthritis onset (P-JCA) with rheumatic factor (RF) negative (n = 29), and P-JCA RF negative with antinuclear antibodies (ANA) positive (n = 13) or negative (n = 16); (4) JCA complicated with chronic anterior uveitis (CAU, n = 32); (5) juvenile psoriatic arthritis (n = 20). To assess the HLA allele frequencies in the above 223 Greek children with JCA, these frequencies were compared to those of 98 age-matched and 250 adult controls. The main findings were the following. A common HLA-DRB1* allele was not involved in the JCA groups and subgroups studied; on the other hand, the DQA1*0501 allele was found to be associated with different JCA groups/subgroups (O-JCA, P-JCA RF-negative ANA-positive, JCA with CAU), probably suggesting a closer relationship of this locus with the immunogenetic background of JCA. The DPB1*0201 allele was associated with the development of either EOO-JCA or CAU. Susceptibility to CAU was stronger when the DPB1*0201 was combined with the presence of DRB1*13. Another allele, DQB1*0301, was also associated with O-JCA and CAU. Finally, no specific HLA class II allele was found to be related to the presence of ANA or psoriatic lesions or to the severity of the arthritis. Our findings suggest that the wide clinical and laboratory spectrum of JCA is associated with an immunogenetic background that is linked with HLA alleles of more than one locus. Some of them, such as the DPB1*0201 allele, confer susceptibility to certain clinical onsets and courses or complications of the disease. The rapidly advancing techniques of typing of DNA profiles may lead to more definite conclusions.

Study of growth hormone secretion and action in growth-retarded children with juvenile chronic arthritis (JCA).

The stimulated and spontaneous growth hormone (GH) secretion and the response to GH action were assessed in growth-retarded children with juvenile chronic arthritis (JCA), in order to determine the underlying mechanisms of growth retardation in such children. Six children (4 boys and 2 girls aged 10.7-13.8 years) with active JCA of systemic onset were included in the study which involved: (1) anthropometric measurements; (2) assessment of GH responses to insulin-induced hypoglycaemia and clonidine stimulation; (3) assessment of the nocturnal pulsatile GH secretion by measuring GH in blood samples obtained every 20 min from 20.00 to 08.00 h; and (4) the IGF-I generation test. As a control, the latter test was also performed in eight aged-matched children with physiological delay in puberty. Biosynthetic hGH (0.1 IU/kg BW) was administered s. c. for 4 days and blood samples were taken at baseline and the morning after the last GH injection for measurement of IGF-I and IGFBP-3. All six children with JCA were prepubertal and their growth velocity was <3 cm/year. The GH responses to both stimulation tests were normal (peak GH >20 mU/l). Analysis of the pulsatile GH secretion during the night revealed three-to-four GH pulses of normal amplitude (>20 mU/l). IGF-I (26.7+/-4.6 nmol/l, mean+/-SD) and IGFBP-3 (2.1+/-0.2 mg/l) levels were lower in the patients compared with the controls (43.0+/-3.7 nmol/l and 2.8+/-0.2 mg/l, respectively, P<0.01). Following stimulation with exogenous hGH, there was a significant increase in IGF-I and IGFBP-3 levels in the control group (85 and 73%, respectively), but only a small increase in the patients (31 and 14%). It appears that stimulated and spontaneous GH secretion is normal in children with active systemic JCA, but the response to endogenous and exogenous GH with regard to IGF-I and IGFBP-3 production is impaired, indicating a degree of GH insensitivity in such children.

Association of the inflammatory state in active juvenile rheumatoid arthritis with hypo-high-density lipoproteinemia and reduced lipoprotein-associated platelet-activating factor acetylhydrolase activity.

OBJECTIVE: To investigate the relationship between the quantitative and qualitative abnormalities of apolipoprotein B (Apo B)- and Apo A-I-containing lipoproteins and between lipoprotein-associated platelet-activating factor acetylhydrolase (PAF-AH) activity in patients with juvenile rheumatoid arthritis (JRA) as a function of the inflammatory state. METHODS: Twenty-six JRA patients and 22 age- and sex-matched control subjects with normal lipid levels participated in the study. Fourteen patients had active disease, and 12 had inactive disease. Plasma lipoproteins were fractionated by gradient ultracentrifugation into 9 subfractions, and their chemical composition and mass were determined. The PAF-AH activity associated with lipoprotein subfractions and the activity in plasma were also measured. RESULTS: Patients with active JRA had significantly lower plasma total cholesterol and high-density lipoprotein (HDL) cholesterol levels as compared with controls, due to the decrease in the mass of both the HDL2 and HDL3 subfractions. Patients with active JRA also had higher plasma triglyceride levels, mainly due to the higher triglyceride content of the very low-density lipoprotein plus the intermediate-density lipoprotein subfraction. The plasma PAF-AH activity in patients with active JRA was lower than that in controls, mainly due to the decrease in PAF-AH activity associated with the intermediate and dense low-density lipoprotein subclasses. The lipid abnormalities and the reduction in plasma PAF-AH activity were significantly correlated with plasma C-reactive protein levels and were not observed in patients with inactive JRA. CONCLUSION: This is the first study to show that patients with active JRA exhibit low levels of HDL2 and HDL3 and are deficient in plasma PAF-AH activity. These alterations suggest that active JRA is associated with partial loss of the antiinflammatory activity of plasma Apo B- and Apo A-I-containing lipoproteins.

Sialochemistry in juvenile chronic arthritis.

Stimulated parotid gland secretions collected from 16 patients with juvenile chronic arthritis (JCA) were analysed and the results compared with those obtained from 83 healthy sex-, age-, and socioeconomic status-matched children. Parotid salivary flow rate was measured and the saliva samples were assayed for calcium, phosphorus, potassium, chloride, sodium, urea, lysozyme, amylase and immunoglobulin levels (IgA, Ig, IgM). Our results showed that parotid flow rate (PFR) values in JCA patients were not statistically different from those in healthy controls. However, the mean salivary concentrations of calcium, phosphorus, potassium, lysozyme and IgA were significantly lower in the patients. These data could provide an explanation for the increased incidence of caries and gingivitis observed in JCA.