Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B cells.

BACKGROUND: B cells play a central role in IgE-mediated allergies. In damaged airway epithelium, they are exposed directly to aeroallergens. We aimed to assess whether direct exposure of B cells to pollen constituents affects allergic sensitization. METHODS: B cells from murine splenocytes and from blood samples of healthy donors were incubated for 8 days under Th2-like conditions with aqueous ragweed pollen extracts (Amb-APE) or its constituents. Secreted total IgM, IgG, and IgE was quantified by ELISA. Additionally, birch, grass, or pine-pollen extracts were tested. The number of viable cells was evaluated by ATP measurements. B-cell proliferation was measured by CFSE staining. IgE class switch was analyzed by quantitation of class switch transcripts. In an OVA/Alum i.p.-sensitization mouse model, Amb-APE was intranasally instilled for 11 consecutive days. RESULTS: Upon Th2 priming of murine B cells, ragweed pollen extract caused a dose-dependent increase in IgE production, while IgG and IgM were not affected. The low-molecular-weight fraction and phytoprostane E1 (PPE1) increased IgE production, while Amb a 1 did not. PPE1 enhanced IgE also in human memory B cells. Under Th1 conditions, Amb-APE did not influence immunoglobulin secretion. The IgE elevation was not ragweed specific. It correlated with proliferation of viable B cells, but not with IgE class switch. In vivo, Amb-APE increased total IgE and showed adjuvant activity in allergic airway inflammation. CONCLUSIONS: Aqueous pollen extracts, the protein-free fraction of Amb-APE, and the pollen-contained substance PPE1 specifically enhance IgE production in Th2-primed B cells. Thus, pollen-derived nonallergenic substances might be responsible for B-cell-dependent aggravation of IgE-mediated allergies.

Pollen-derived adenosine is a necessary cofactor for ragweed allergy.

BACKGROUND: Ragweed (Ambrosia artemisiifolia) is a strong elicitor of allergic airway inflammation with worldwide increasing prevalence. Various components of ragweed pollen are thought to play a role in the development of allergic responses. The aim of this study was to identify critical factors for allergenicity of ragweed pollen in a physiological model of allergic airway inflammation. METHODS: Aqueous ragweed pollen extract, the low molecular weight fraction or the major allergen Amb a 1 was instilled intranasally on 1-11 consecutive days, and allergic airway inflammation was evaluated by bronchoalveolar lavage, lung histology, serology, gene expression in lung tissue, and measurement of lung function. Pollen-derived adenosine was removed from the extract enzymatically to analyze its role in ragweed-induced allergy. Migration of human neutrophils and eosinophils toward supernatants of ragweed-stimulated bronchial epithelial cells was analyzed. RESULTS: Instillation of ragweed pollen extract, but not of the major allergen or the low molecular weight fraction, induced specific IgG1 , pulmonary infiltration with inflammatory cells, a Th2-associated cytokine signature in pulmonary tissue, and impaired lung function. Adenosine aggravated ragweed-induced allergic lung inflammation. In vitro, human neutrophils and eosinophils migrated toward supernatants of bronchial epithelial cells stimulated with ragweed extract only if adenosine was present. CONCLUSIONS: Pollen-derived adenosine is a critical factor in ragweed-pollen-induced allergic airway inflammation. Future studies aim at therapeutic strategies to control these allergen-independent pathways.

Feasibility of a multdisciplinary lung cancer videoconference between a peripheral hospital and a comprehensive cancer centre.

OBJECTIVE: Treatment of lung cancer patients is changing rapidly and new treatment options have emerged in recent years. In 2007, to guarantee the best treatment procedure for lung cancer patients being treated in our peripheral hospital, we decided to introduce an interdisciplinary tumour videoconference between the Haemato-Oncological Day Hospital in Merano and the Comprehensive Cancer Centre Innsbruck. This retrospective analysis aims to describe the feasibility of such a conference. PATIENTS AND METHODS: Two hundred and three patients with lung cancer treated at the peripheral hospital of Merano between May 2003 until May 2011 were retrospectively analysed. After introduction of the tumour videoconference in 2007, 54% (n = 110) of the patients in this cohort were discussed in the conference. RESULTS: One hundred and four videoconferences were performed. Videoconference was feasible for 110 patients. Radiotherapeutic treatments were prescribed more frequently in patients from the conference group. Overall, major and minor treatment changes were undertaken in 7% (n = 8) and 18% (n = 20), respectively. CONCLUSION: Interdisciplinary tumour videoconference is feasible between a peripheral hospital and a comprehensive cancer centre. Radiotherapeutic treatment was prescribed more frequently, suggesting that such a conference facilitates the access to cancer-centre-specific treatment modalities. Accordingly, tumour videoconference between a peripheral hospital and a cancer centre is to be recommend.

Hip simulator wear testing according to the newly introduced standard ISO 14242.

Ultra-high molecular weight polyethylene (UHMWPE) acetabular cups were tested against alumina-ceramic femoral heads using a new type of hip joint simulator according to ISO/FDIS 14242-1. Bovine serum as well as newborn calf serum were used as test fluids. Total polyethylene wear was determined by weight loss of the cups. In addition. wear depth and its distribution were recorded by means of a coordinate measurement system. Wear particle analysis and inspection of the worn polyethylene surfaces using light and scanning electron microscopy (SEM) were performed to analyse damage and identify the acting wear mechanisms. The total wear rate was determined to be 22.07 +/- 1.75 mg/10(6) cycles for the bovine serum group and 26.57 + 3.55 mg/10(6) cycles for the calf serum group. Unexpectedly, the formation of two wear vectors corresponding to recent clinical findings was detected. Retrieved polyethylene wear debris was comparable in size and shape with clinical findings. The test method described by ISO/FDIS 14242-1 produced reliable and reproducible wear data using UHMWPE acetabular cups articulating against alumina-ceramic heads. In the authors' opinion, the lubricant composition should be described in more detail, since the protein and additive content seem to have a high impact on the wear results. It needs to be emphasized that the findings of this study cannot be regarded as a general validation of hip wear tests according to ISO/FDIS 14242-1 but are limited to the material combinations investigated herein. Further testing of other clinically relevant materials and interlaboratory ring tests must follow.

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Iron supplementation in children after cardiopulmonary bypass for surgical repair of congenital heart disease.

A controlled study was carried out to evaluate the effects of postoperative iron therapy on iron status in anemic children after cardiopulmonary bypass. The patients were 8 boys and 9 girls (mean age 6.5 years) who underwent elective closure of atrial septal defect, secundum type. On postoperative day 9, patients were randomly assigned to either iron supplementation with iron sulfate 5 mg/kg until day 56 or to a control group. Hemoglobin, reticulocytes, transferrin saturation, free erythrocyte protoporphyrin, and ferritin were measured, the final outcome measure being postoperative iron status on day 56. The treatment group showed higher transferrin saturations (33.5% versus 18.0%), smaller decreases in ferritin level (+3.0 versus--13.7 ng/ml), and a lower incidence of depleted iron stores (0/8 versus 5/9) than the control group (all data: P < 0.05). Anemic children after cardiopulmonary bypass for surgical repair of congenital heart disease thus benefit from iron supplementation within the first postoperative weeks.

Long-term hemodynamic effects of nifedipine on congenital heart disease with Eisenmenger's mechanism in children.

The hemodynamic effect of long-term nifedipine medication was studied in 10 children, 3-12 years of age, five with ventricular septal defect and five with complete atrioventricular septal defect; all had Eisenmenger's reaction, seven also had Down's syndrome. They underwent heart catheterization prior to and during 1-4 years of nifedipine therapy. Fick's principle was used to calculate the ratio of pulmonary arterial pressure to aortic pressure (PAP/PAO), the ratio of pulmonary flow to aortic flow (QP/QS), as well as the ratio of pulmonary vascular resistance to aortic vascular resistance (RP/RS). In the seven children under 8.8 years, nifedipine caused a significant drop in PAP/PAO (p less than 0.004), a slight increase in arterial O2 saturation, a significant increase in QP/QS (p less than 0.02), and a decrease in RP/RS (p less than 0.02). The nifedipine effect was age related. On nifedipine, breathing oxygen resulted in, independent of age, a significant increase in QP/QS (p less than 0.003) and a significant decrease in PAP/PAO (p less than 0.04) and in RP/RS (p less than 0.003). Direct O2 consumption measurements before and during oxygen breathing in six patients demonstrated no significant change in RP, RS, QP, or QS indices. Nifedipine had a relaxing effect on the pulmonary vascular bed, especially in the younger child with Eisenmenger's mechanism. On nifedipine therapy, O2 produced a more complex hemodynamic reaction that was not restricted to the pulmonary circulation alone.

Experience with long-term nifedipine therapy in paediatric cardiological patients.

Clinical experience with long-term nifedipine treatment in 23 patients aged between 1 1/12 and 14 8/12 years is reported. The cardiopulmonary diseases comprised primary pulmonary diseases with pulmonary hypertension (n = 4), congenital heart defects with intracardiac shunts and pulmonary hypertension which either were inoperable as a result of an Eisenmenger reaction (n = 7) or presented a high surgical risk (n = 5), or defects in which pulmonary hypertension did not regress despite corrective (n = 1) or palliative surgery (n = 3), and congenital defects without pulmonary hypertension (n = 3). Subjective improvement with an increase in physical performance was clearly observed in 15 cases. Echocardiography and cardiac catheter examinations showed no progression of the pulmonary arterial diseases, except in 1 patient with severe primary pulmonary hypertension and an 11-year observation period with nifedipine treatment during the last 4 years. No complications occurred during the 4 corrective operations. A patient aged 14 8/12 years with the Down syndrome and atrioventricular septal defect developed easily controllable heart failure during 7-day administration of nifedipine without additional cardiotherapy. 4 children initially suffered from flushed face and scalp, in one case with headache; 2 children reported fatigue. Long-term treatment with nifedipine should begin with strict 7-day supervision in hospital and possibly additional digitalization. Success of the treatment was determined by an improved quality of life in patients with primary pulmonary hypertension and inoperable defects, and by a reduced perioperative risk and postoperative regression of pulmonary hypertension in patients with operable defects.

Histological grading of therapy induced regression in squamous cell carcinomas of the oral cavity. A morphological and immunohistochemical study.

Squamous cell carcinomas in the oral cavity and the oropharynx were diagnosed in 84 patients. After verification by biopsy, 79 of these patients were treated preoperatively with mitomycin C and 5-fluro-uracil, radiated and operated 3-5 weeks later. The effectiveness of adjuvant preoperative radio-chemotherapy was evaluated histologically. Serial sections of the entire tumor specimen were investigated and the percentage of vital cancerous tissue in the total tumor area was assessed. Regression was classified into four grades. Grades I and II were regarded as good response to adjuvant preoperative radio-chemotherapy, while grades III and IV stood for bad or no response. Morphologically questionable residual tumor infiltrates could be clarified by immunohistochemical methods with antibodies against vimentin, desmin and Lu-5. The histological assessment of the regression grade of operated tumor specimens allows a clinically relevant, morphologically exact and reproducible evaluation of the effect of preoperative radiochemotherapy.

Hemodynamic effects of nifedipine and oxygen in children with pulmonary hypertension.

Fourteen patients, 2 to 20 years old were investigated. Two had primary pulmonary hypertension, 11 had congenital heart disease and post-tricuspid shunts, and 1, a 20-year-old patient, was investigated after he had undergone surgical correction of truncus arteriosus I. Pulmonary arterial pressure, pulmonary flow index, peripheral systolic blood pressure and heart rate were measured before, and several times after intrapulmonary injection into the pulmonary artery of 0.5 microgram nifedipine/kg. Six patients were given an additional dose of 1 microgram nifedipine per kilogram into the pulmonary artery and hemodynamic measurements were repeated. In eight children, receiving 100% oxygen via a breathing mask, nifedipine effects were compared with oxygen effects. After 10 minutes under oxygen, the same hemodynamics were determined as after nifedipine. In addition, in four of these children aortic pressure and arterial oxygen saturation were also measured. Maximal effects occurred within 4 minutes. 0.5 micrograms nifedipine per kilogram caused a slight reduction in mean pulmonary arterial pressure (p less than 0.05), as well as increase in pulmonary flow index (p less than 0.005). However, no significant change in heart rate or in systolic blood pressure was observed. 1 microgram nifedipine per kilogram IP had almost the same effects. No adverse side effects occurred, besides mild headaches in one child. A comparison of nifedipine injected into the pulmonary artery with oxygen breathing in congenital heart disease combined with pulmonary hypertension, is reported for the first time. Nifedipine had a more pronounced and beneficial effect with a selective action on the pulmonary vascular bed.

[Hemodynamic studies of nifedipine (Adalat) in pulmonary hypertension in childhood]. / Hämodynamische Untersuchungen von Nifedipin (Adalat) bei pulmonaler Hypertension im Kindesalter.

Under long-term oral treatment with nifedipine (N) 2 of 3 patients (2 children with VSD and Eisenmenger, 1 patient with Truncus I after corrective surgery) showed a remarkable improvement in exercise tolerance and reduction in the total pulmonary resistance. Therefore a single-dose testing with N was performed in 9 patients aged 2 to 20 years with primary pulmonary hypertension (n = 2), secondary pulmonary hypertension because of congenital heart disease with intracardiac shunts (n = 6) and after correction of Truncus Type I (n = 1). Before and after the injection of 0.5 mcg/kg of N into the main pulmonary artery, pulmonary artery pressure, cardiac output and systolic blood pressure were measured at 1 minute intervals during right heart catheterization. The maximal reaction occurred 3 to 4 minutes after the injection. The total pulmonary vascular resistance decreased significantly from 2684.2 +/- 1829.2 to 1300.2 +/- 1117.0 dyn.sec.cm-5.m2 (p less than 0.025), the cardiac index increased significantly from 3.1 +/- 1.65 to 5.73 +/- 1.95 l/min.m2 (p less than 0.01) concomitantly with a mild reduction in the mean pulmonary artery pressure. No significant change in heart rate and systolic blood pressure was seen; no side effects were observed. 4 of the 5 patients with the highest pulmonary vascular resistance showed the best positive reactions. Therefore these 9 patients may benefit from a long-term oral treatment with nifedipine.