Low levels of immunoglobulin A in children with intrinsic asthma: a possible protection against atopy

Immunoglobulin A and G (IgA, IgG) serum concentrations were detected in children with nonallergic/intrinsic (36 children) or allergic/extrinsic asthma (43 children) and in age-matching control children (40 children). Asthmatic children with allergic asthma had lower IgA (1.36+/-0.54 g/L) and higher IgG (10.48+/-2.77 g/L) levels than the age-matching control children group (1.63+/-0.69 vs. 9.01+/-2.32 g/L). Children with nonallergic/intrinsic asthma had lower IgA (1.03+/-0.41 g/L) ( p = 0.004) and IgG (8.38+/-1.93 g/L) (p = 0.001) levels than the allergic/extrinsic asthma group (1.36+/-0.54 vs. 10.48+/-2.77 g/L). Low IgA levels were found in children with nonallergic/intrinsic asthma and high IgG levels were found in those children with allergic/extrinsic childhood asthma. The hypothesis is that the increased incidence of asthma in the population may be caused by a decrease in childhood infections (hygiene hypothesis). Frequent infections in early life boost the immune system, stimulating Th1-type response in young children and reducing the risk of atopic diseases. Our hypothesis is that low IgA (and/or IgG) levels in our patients might be responsible for infection development among those children with nonallergic/intrinsic asthma. These infections stimulate the normal development of immune system in young children, reducing risk of atopy, so that those children do not get allergic/extrinsic childhood asthma. Intrinsic childhood asthma=nonallergic (nonatopic) childhood asthma. Extrinsic childhood asthma=allergic (atopic) childhood asthma.     

Determination of mandelic acid enantiomers in urine by gas chromatography and electron-capture or flame ionisation detection

A sensitive and stereospecific GC method was developed for the analysis of R- and S-enantiomers of mandelic acid (MA) in urine, using a chiral CP Chirasil-Dex-CB column. The enantiomers of MA were derivatised with isopropanol into their corresponding isopropyl esters and determined either directly with flame ionisation detection (FID) or after subsequent derivatisation of a hydroxy group with pentafluoropropionic anhydride with electron-capture detection (ECD). Both derivatisation steps proceeded with negligible inversion of enantiomers (<1%). The limit of detection of the FID determination was 8 and 5 mg/l for R-MA and S-MA, respectively and of the ECD determination 1 mg/l for both enantiomers. Repeatability (within-day precision) and reproducibility (day-to-day precision) was for both enantiomers below 7.5% for the FID and below 5.8% for the ECD analysis. The method was applied to urine of volunteers exposed to 105 and 420 mg styrene/m3 air. In the urine of the exposed volunteers, the S-enantiomer showed higher excretion compared to that of the R-enantiomer, with marked interindividual differences in excretion of both enantiomers.     

Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab

INTRODUCTION: The purpose of this study was to determine the effect of repeated infusions of infliximab, a chimeric anti-tumor necrosis factor (anti-TNF)-alpha antibody, on the levels of soluble adhesion molecules and vascular endothelial growth factor (VEGF) in patients with active rheumatoid arthritis (RA). MATERIALS AND METHODS: The treatment design consisted of 9 infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. All patients had been receiving methotrexate (MTX; 7.5-20 mg/week). Serum levels of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, E-selectin (sE-selectin), and VEGF were measured by ELISA at weeks 0, 2, 6, 14, and 38 prior to infusion, and at week 62. RESULTS: A remarkable decrease in serum sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01) and VEGF (p<0.001) levels was observed in RA patients after the initial dose of infliximab. The second administration of the drug was followed by an even more significant suppression of serum sICAM-1, sVCAM-1, sE-selectin, and VEGF (p<0.001 in all cases). Further infliximab infusions also significantly reduced serum soluble adhesion molecules and VEGF concentrations, although these were less effective. Infliximab treatment induced a significant decrease in the number of monocytes observed until the end of the study. CONCLUSIONS: Our study, besides a rapid suppression of disease activity, showed that serum soluble adhesion molecules and VEGF concentrations are down-regulated following anti-TNF-alpha antibody therapy combined with MTX. Repeated doses of infliximab sustained the reductions in the soluble adhesion molecules and VEGF concentrations, although they were less effective than the first and second infusions of infliximab.     

Cytokines in patients with lung cancer

Lung cancer is one of the most common malignant diseases and is amongst the leading causes of death. Cell-mediated immune response and cytokines could play an important role in antitumour immunity. The aim of the study was to evaluate the cytokines', tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6, releasing capacity in patients with lung carcinoma and benign lung disease. A group of 41 patients were tested for the production of TNF-alpha, IL-1beta and IL-6 in bronchoalveolar lavage (BAL) and blood. The levels of cytokines in the lung cancer patients were: (1) in BAL - IL-6, 173 +/- 85 pg/ml; TNF-alpha, 170 +/- 116 pg/ml; and IL-1beta, 473 +/- 440 pg/ml; (2) in the blood - IL-6, 197 +/- 53 pg/ml; TNF-alpha, 311 +/- 202 pg/ml; and IL-1beta, 915 +/- 239 pg/ml. Alveolar macrophages of the patients with a lung cancer secreted significantly more cytokines, IL-6 (P = 0.0004) and IL-1beta (P = 0.0047), than alveolar macrophages of the patients with a nonmalignant lung cancer. However, significantly lower levels of cytokine production by the BAL cells were found in patients with small cell lung cancer. This production decreased further in phase IV of nonsmall cell lung cancer.     

Malignant lymphoma of the stomach in association with inflammatory myofibroblastic tumor of the spleen. A case report

We report on a case of a 40-year-old male patient who underwent a gastrectomy because of a biopsy-proven large B-cell lymphoma of the stomach. On surgery, a nodule in the spleen also was noted. Grossly and microscopically, the two lesions were different: the tumor of the stomach appeared white-gray on the cut surface and was a centroblastic variant of diffuse large B-cell lymphoma. Histologically, one perigastric lymph node was involved. Grossly, the splenic nodule was gray-yellow and had a histological appearance of an inflammatory myofibroblastic tumor (IMT). The association between malignant tumor and IMT is rare. In such an association, the latter lesion most often has been reported in the spleen. As EBV may be involved in the genesis of both lymphoma and IMT, we tested both lesions for its presence using in situ hybridization, but the tests were negative. It remains to be verified whether the association between lymphoma and IMT is more than fortuitous.