Treatment of severe primary IGF-1 deficiency using rhIGF-1 preparation - first three years of Polish experience.

INTRODUCTION: The objective of this study was to analyse the effects of the first three years of treatment with recombinant human insulinlike growth factor 1 (rhIGF-1) in patients from the Polish population. MATERIAL AND METHODS: Twenty-seven children (22 boys and five girls) aged 2.8 to 16.0 years old were qualified for treatment with rhIGF-1 (mecasermin) in different treatment centres, according to Polish criteria: body height below -3.0 SD and IGF-1 concentration below percentile 2.5 with normal growth hormone (GH) levels. Mecasermin initial dose was 40 µg/kg bw twice a day and was subsequently increased to an average of 100 µg/kg bw twice a day. Body height, height velocity, weight, body mass index (BMI), and adverse events were measured. RESULTS: Mecasermin treatment resulted in a statistically significant increase in body height (1.45 ± 1.06 SD; p < 0.01) and height velocity in comparison with pre-treatment values. The biggest change in height velocity happened during the first year and diminished during subsequent years. Body weight and BMI also increased significantly after treatment (1.16 ± 0.76 SD and 0.86 ± 0.75 SD, respectively; p < 0.01). Eight patients reported adverse events. These were mild and temporary and did not require treatment modification except in two patients. CONCLUSIONS: Treatment with rhIGF-1 was effective and safe in Polish patients with primary IGF-1 deficiency. It had a clear beneficial effect on the height of the patients and significantly accelerated the height velocity, particularly in the first year of treatment.

[Early atherosclerosis changes in children with juvenile idiopathic arthritis]. / Wczesne zmiany miazdzycowe u dzieci chorych na mlodziencze idiopatyczne zapalenie stawów.

UNLABELLED: Pathogenesis of the two diseases: juvenile idiopathic arthritis (JIA) and atherosclerosis are similar-they include increased inflammation markers, homocysteine and lipids levels, inflammatory cytokines. It seems to be important to look for new diagnostic methods to find atherosclerosis in early stage- ultrasonography of the carotid artery with intima-media thickness (IMT) measurement and serum homocysteine level. The aim of this study was assessment of preclinical markers of atherosclerosis--concentration of homocysteine and IMT MATERIAL AND METHODS: The study group consists of 40 children with JIA (20 girls and 20 boys) aged 4-16 years; 32 children with oligoarthritis JIA and 8--polyarthritis JIA. Control group consists of 23 healthy children aged 3-17 years. We investigated serum levels of homocysteine, CRP, lipids and also IMT of the carotid artery. Children with JIA had statistically significant increase of IMT compare to control group (0.43 mm vs. 0.40 mm) and higher IMT in polyarthritis group compare to oligoarthritis children (0.46 mm vs. 0.43 mm). We also find statistically significant correlation between IMT and disease duration (p = 0.003, r = 0.45). RESULTS: Children with JIA had also statistically significant increase of homocysteine level compare to control group (8.2 micromol/l vs. 6.05 micromol/l) and higher homocysteine level in polyarthritis group compare to oligoarthritis children (8.58 micromol/l vs. 7.88 micromol/l). We also find statistically significant correlation between IMT and homocysteine level (p = 0.02, r = 0.36). CONCLUSIONS: There is accelerated atherosclerosis in JIA children that's why we need to find new methods to evaluate it in very early stage so we could help these patients to prevent its complication such as heart disease, stroke etc in the future.

[Composition of linoleic and arachidonic acids in phosphatidylcholine of erythrocytes membrane and IL-6 and TNF-alpha in serum and C-reactive protein concentration in children with juvenile idiopathic arthritis]. / Zawartosc kwasu linolowego i arachidonowego w fosfatydylocholinie blon erytrocytarnych oraz IL-6 i TNF-alpha w surowicy a stezenie bialka C-reaktywnego u dzieci chorych na mlodziencze idiopatyczne zapalenie stawów.

UNLABELLED: The study objective was to determine the relationship, if any, between the levels of arachidonic and linoleic acids in erythrocyte membrane phosphatidylcholine (PCH), serum interleukin 6 (IL-6) and TNFalpha levels and C-reactive protein (CRP) in juvenile idiopathic arthritis (JIA). MATERIALS AND METHODS: The study involved 49 children with JIA, aged 3-18 years (mean 11.3 +/- 3.9), and 29 healthy subjects. The JIA children were divided into 2 groups: group I--24 children (in exacerbation period) with mean CRP level of 15.6 mg/L +/- 13.3 and group II--25 children (in remission period--joint swelling-free) with CRP of 7.8 mg/L +/- 5.8 on average. Lipids were extracted according to a modified Folch's method. Fatty acids in erythrocyte membrane PCH were identified using gas chromatography (Hewlett-Packard 5890). The levels of IL-6 and TNFalpha were determined by ELISA, using Quantikine sets: R&D System (USA), while CRP was measured by nephelometric method on a BN II apparatus (Behring). RESULTS: We found a significant decrease in the level of linoleic acid (p < 0.05) and a statistically insignificant reduction in arachidonic acid in JIA patients as compared to the controls. The decrease in linoleic acid was more pronounced in the active phase of JIA (p < 0.001. The higher serum CRP level was accompanied by a significantly elevated level of IL 6 (p < 0.05). The concentration of TNFa was elevated, but the difference had no statistical significance. CONCLUSIONS: The levels of linoleic and arachidonic acids in erythrocyte PCH decreased and the concentrations of IL-6 and TNF-alpha increased in JIA children in the active phase of the disease. The differences intensified with a rise in CRP.

[Cytokine levels in serum of patients with juvenile idiopathic arthritis depending on subtype and disease activity]. / Stezenie cytokin w surowicy u chorych z mlodzienczym idiopatycznym zapaleniem stawów w zaleznosci od postaci choroby i stopnia jej aktywnosci.

We investigated serum levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) in 25 patients with juvenile idiopathic arthritis (JIA) during both: active and inactive phases of the disease. The polyarticular JIA patients had the highest IL-6 level during both active and inactive periods, TNFalpha level was the highest in the systemic JIA, active and inactive periods. IL-6 and TNFalpha levels were significantly lower than those of controls (p<0.0003) in oligoarticular JIA. IL-6 correlated significantly with C-related protein (CRP) in active period (p<0.001) and inactive period (p<0.05) in oligoarticular JIA patients, such correlation was not found for TNFalpha. In conclusion, IL-6 and CRP may play an important role in JIA and may be used as a marker of disease activity.

[Lipids and homocysteine level in juvenile idiopathic arthritis]. / Ocena wybranych parametrów gospodarki lipidowej i homocysteiny w mlodzienczym idiopatycznym zapaleniu stawów u dzieci.

We investigated serum levels of lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglicerides), homocysteine, C-reactive protein (CRP) in 25 children with juvenile idiopathic arthritis (JIA) and 15 healthy control. We found statistically significant increase of total cholesterol, LDL-cholesterol, triglicerides (p<0.05) and decreased of HDL-cholesterol (p<0.05) in JIA patients compare to control group. Homocysteine correlated significantly with total cholesterol (r=0.47; p<0.05) and with LDL-cholesterol (r=0.53; p<0.05). In JIA children we found adverse lipids profile and increase of homocysteine level which may lead to early atherosclerosis.

[Correlation between intima-media thickness in carotid artery and markers of epithelial cell dysfunction in patients with juvenile idiopathic arthritis]. / Ocena zaleznosci pomiedzy gruboscia warstwy wewnetrznej i sródblonka u dzieci z mlodzienczym idiopatycznym zapaleniem stawów (MIZS).

UNLABELLED: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Prolonged immunological inflammatory process leads in these patients to an early onset of atherosclerosis. That is why it seems to be important to find methods of detecting atherosclerosis in its very early stage to start appropriate treatment. AIM: The aim of this study was to determine whether there is any correlation between intima-media thickness (IMT) in carotid artery and concentrations of markers of epithelial cell dysfunction - C-reactive protein and Intercellular Adhesive Molecule -1 (sICAM-1). MATERIALS AND METHODS: 63 children were enrolled in the study (40 with JIA and 23 healthy as control group). C-reactive protein concentration was assayed by immunoturbidimetric method with Hitachi 912 Chemistry Analyzer and sICAM-1 was assayed by ELISA. IMT was measured as defined by Pignoli. RESULTS: Mean CRP concentration in the study group was 1.97 mg/dl and in the control group -0.08 mg//dl. sICAM-1 concentration was 333.4 mg/ml, and mean IMT in carotid artery in children with JIA was 0.43 mm (max=0.58 mm, min=0.36 mm). There was a correlation between IMT and sICAM-1 concentration (r=0.75, p<0.001). CONCLUSIONS: Assessment of IMT in carotid artery and concentrations of sICAM-1 and CRP may be used as a marker of preclinical arthrosclerosis in children with JIA.