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D Y Koller

Publications and source records attributed to D Y Koller.

34 records · Page 2Linked to original sources
PubMed1997

Urinary eosinophil protein X in relation to disease activity in childhood asthma.

The clinical use of urinary eosinophil protein X (U-EPX) measurements in monitoring inflammation in childhood asthma was investigated. U-EPX and pulmonary function were assessed in 80 children with bronchial asthma and 24 healthy, age-matched controls. In addition, 14 patients with asthma were re-examined after 1-2 months. U-EPX levels were increased in children with asthma compared with controls (median 68.4 vs 35.3 micrograms/mmol creatinine; P < 0.0001). In addition, U-EPX levels were higher in symptomatic than in asymptomatic patients (median 123.5 vs 48.9 micrograms/mmol creatinine; P < 0.0001) independent of treatment modalities (i.e., inhaled steroids or disodium cromoglycate) or atopy (median 65.1 vs 86.0 micrograms/mmol creatinine). Furthermore, U-EPX levels were significantly correlated with pulmonary function. During the follow-up period, changes in U-EPX values were significantly related to changes in pulmonary function. In conclusion, our findings demonstrate that eosinophil activation can be measured in urine in childhood asthma. Concentrations of U-EPX are related to disease activity and pulmonary function, as shown in both cross-sectional and longitudinal analyses, but are independent of atopy and treatment modalities. Measurement of U-EPX may be useful in assessing the inflammatory process and therefore in the management of childhood asthma.

Adolescent↗
PubMed1997

Cytokine concentrations in sputum from patients with cystic fibrosis and their relation to eosinophil activity.

To evaluate whether concentrations of cytokines supposed to be involved in eosinophil recruitment and activation were elevated in cystic fibrosis (CF), we assessed interleukin-3 (IL-3), IL-5, IL-8, regulated on activation, normal T-cell expressed and secreted (RANTES); and granulocyte-macrophage colony stimulating factor (GM-CSF) in sputa from 32 patients with CF, eight patients with atopic bronchial asthma, and six patients with bacterial pneumonia. In addition, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as markers of eosinophil activation. In patients with CF, sputum levels of IL-8 were elevated (p < 0.01) as compared with asthmatic patients. Concentrations of IL-3, ECP, and EPX were not different in the two groups. However, IL-5 (p < 0.0001), RANTES (p < 0.003), and GM-CSF (p < 0.0001) were significantly lower in the CF group than in subjects with asthma. IL-5 was detected only in sputum samples from CF patients with Aspergillus sensitization. In patients with pneumonia, IL-8 levels only were increased. In CF sputum, ECP levels were significantly correlated with the levels of IL-8 (r = 0.626, p < 0.0001) and IL-3 (r = 0.642; p < 0.0001), whereas in asthmatic patients IL-5, IL-8, and RANTES concentrations were significantly related to ECP in sputum. These findings suggest that different cytokine profiles are responsible for eosinophil activation in patients with CF as compared with asthmatic patients. In CF, IL-8 and IL-3 appear to be responsible for increased degranulation of eosinophils.

Adolescent↗
PubMed1997

Sensitization to Aspergillus fumigatus and lung function in children with cystic fibrosis.

Colonization with Aspergillus fumigatus (Af) constitutes a common finding in children with cystic fibrosis (CF). The relationship between sensitization to Af and lung functon (LF) was studied in 118 patients with CF (61 girls and 57 boys; mean age: 14.3 yr; SD: 7 yr). Mean follow up was 2.2 yr. On average, 8.1 (SD: 4.8) LF tests were performed per patient. Measurement of total IgE and specific IgE antibodies to Af, and a skin prick test (SPT) for Af, were done once a year. Thirty-one children (26%) were sensitized to Af. On average, LF parameters were not significantly different in Af-sensitized children than in nonsensitized children. Linear regression analyses were performed, using the repeated measures design. With adjustment for gender, age, height, and weight, sensitization to Af was associated with lower values of FEV1 (beta = -0.209; p < 0.05) and FEF(25-75) (beta = -0.356; p < 0.01). Analysis of different subgroups of sensitization demonstrated the effect on LF only in Af-sensitized patients with elevated total IgE levels, and not in Af-sensitized patients with normal IgE levels. Furthermore, there was evidence for a more rapid decline in LF for Af-sensitized patients with elevated total IgE levels than in those with normal IgE levels. We conclude that sensitization to Af in the presence of increased IgE values is associated with lower LF values in children with CF.

Adolescent↗
PubMed1996

Decreased tumor incidence and increased survival by one year oral low dose arginine supplementation in the mouse.

The effects of arginine on tumor growth, antitumor mechanisms and a potential therapeutic role have been reviewed recently. In these studies, however controversial they were, high dose protocols for arginine treatment have been applied. Based upon own recent findings that low dose arginine stimulates the immune system and blocks lipid peroxidation, we performed preventive treatment with low dose (50 mg/kg body weight per day, orally administered) L-arginine in 150 mice for a period of one year. We compared survival and total number of tumors at the end of the feeding period to that found in 150 mice given taurine in the same dosage and in 150 mice without treatment. Survival of the arginine treated group was statistically significant as compared to that of the control group without treatment (p < 0.05): 116 mice were alive in the control group, 122 in the group administered taurine and 132 in the arginine treated group. The total number of tumors was significantly lower in the arginine treated group vs. the control group (p < 0.01). The total number of malign and benign tumors was significantly lower in the arginine treated group, whereas taurine significantly reduced the number of benign tumors only (p < 0.05). Arginine and taurine stimulate the immune system at the lymphocyte level. Arginine also acts at the macrophage level, inducing nitric oxide mediated cytotoxicity against tumor cells. Both compounds are known to block the formation of lipid peroxidation products. We therefore suggest that these two mechanisms are responsible for the decreased total number of tumors and the concomitant increase in survival.

Animals↗
PubMed1996

Relationship between disease severity and inflammatory markers in cystic fibrosis.

To evaluate the clinical use of measuring neutrophil, lymphocyte, and eosinophil activities, serum myeloperoxidase (MPO), soluble interleukin-2 receptors (sIL-2R), and eosinophil cationic protein (ECP) were measured in 98 patients with cystic fibrosis and in 85 healthy children. Serum concentrations of MPO, sIL-2R, and ECP were increased in patients with cystic fibrosis (median 807 micrograms/l, 4452 pg/ml, 48.8 micrograms/l, respectively) compared with the controls (median 319 micrograms/l, 2743 pg/ml, 9.4 micrograms/l). ECP concentrations, but not serum MPO or sIL-2R, were significantly related to disease severity assessed by the Shwachman-Kulczycki score and by pulmonary function (forced expiratory volume in one second % predicted). Neither ECP nor sIL-2R was influenced by Pseudomonas aeruginosa infection, acute pulmonary exacerbation, or atopy. Serum MPO, however, was strongly correlated with acute pulmonary exacerbation. In the light of these findings the measurement of serum ECP might thus be used for clinical monitoring and for assessing disease severity in cystic fibrosis. The measurement of serum MPO and sIL-2R did not correlate with the disease severity.

Biomarkers↗
PubMed1995

Clinical value of monitoring eosinophil activity in asthma.

To evaluate the use of eosinophil cationic protein (ECP) in monitoring disease activity in childhood asthma, serum ECP in 175 asthmatic children was assessed. Forty five patients with cystic fibrosis, 23 with lower respiratory tract infections (LRTI), and 87 healthy children were used as controls. Serum ECP concentrations (34.3 micrograms/l v 9.8 micrograms/l) were significantly higher in children with bronchial asthma than in healthy control subjects. In symptomatic patients with asthma serum ECP concentrations were increased compared with those from asymptomatic patients (40.2 micrograms/l v 14.4 micrograms/l), irrespective of treatment modalities (that is steroids, beta 2 agonists, or sodium cromoglycate). Moreover, atopy and infection appeared to be factors enhancing eosinophil activity in bronchial asthma as measured by serum ECP (58.4 micrograms/l v 36.8 micrograms/l and 68.8 micrograms/l v 42.2 micrograms/l, respectively). In a longitudinal trial, antiasthmatic treatment modalities (that is steroids) reduced serum ECP within four weeks (42.2 micrograms/l v 19.0 micrograms/l). In conclusion, the data indicate that (1) eosinophils also play a central part in childhood asthma; (2) serum concentrations of ECP in children with bronchial asthma are related to the disease severity and may thus be used for monitoring inflammation in childhood asthma; (3) eosinophil activity appears to be enhanced by atopy and infection; and (4) longitudinal measurements of serum ECP concentrations may be useful for optimising anti-inflammatory treatment in children with bronchial asthma.

Albuterol↗
PubMed1995

Increased degranulation of eosinophil and neutrophil granulocytes in cystic fibrosis.

Increased serum and sputum concentrations of eosinophil cationic protein (ECP) and of neutrophil myeloperoxidase (MPO) have been described in patients with cystic fibrosis. Because numbers of eosinophils are normal in both peripheral blood and in the lung of patients with cystic fibrosis, we investigated whether eosinophils presented with an increased propensity to release their granule proteins. We investigated 20 patients with cystic fibrosis, 19 individuals with bronchial asthma, and 21 healthy nonatopic subjects. Isolated granulocytes were stimulated with serum-opsonized Sephadex G15 particles and the released amounts of ECP and MPO were measured by using radioimmunoassays. Eosinophils of patients with cystic fibrosis released significantly higher amounts of ECP than control subjects (p < 0.0001) and individuals with bronchial asthma (p < 0.0001). The release of MPO from neutrophils was also higher (p < 0.0001 and p < 0.005, respectively). Furthermore, a significant relationship between clinical variables and secretory activity of eosinophils was found in cystic fibrosis. We conclude that eosinophils as well as neutrophils obtained from patients with cystic fibrosis have an increased propensity to release their granule proteins which may be due to priming mechanisms. These findings would support anti-inflammatory treatment modalities in cystic fibrosis.

Adolescent↗
PubMed1994

Eosinophilic activation in cystic fibrosis.

BACKGROUND: The neutrophil is a potent contributor to pulmonary destruction in cystic fibrosis. Since eosinophils also possess destructive potential the involvement of eosinophils in cystic fibrosis has been investigated. METHODS: Eosinophil numbers and levels of eosinophil cationic protein (ECP), a marker of eosinophil activation, were determined in the serum of 42 patients with cystic fibrosis and in the sputum of 10 of them. To determine neutrophil activation levels of myeloperoxidase (MPO) were also measured. RESULTS: In cystic fibrosis increased serum levels of ECP were detected compared with healthy non-atopic subjects. Serum ECP levels were not related to the peripheral blood eosinophil count. A strong correlation with ECP concentrations in sputum indicated that the level of ECP in serum was representative of its pulmonary level. Levels of MPO were also increased in cystic fibrosis. A strong correlation was found between MPO and pulmonary function. In addition, ECP was related to arterial oxygen and carbon dioxide tensions. Antibiotic treatment reduced neutrophil activation without effect on ECP levels. CONCLUSIONS: Until now Pseudomonas aeruginosa and neutrophils were held to be primarily responsible for progressive tissue damage in cystic fibrosis. The results of this study suggest that eosinophils might also participate in such pulmonary destruction.

Adolescent↗
PubMed1993

Immuno-allergologic aspects of childhood asthma.

Asthma has a major impact on the health of children. Airway inflammation and bronchial hyperresponsiveness of variable severity have presently come to be considered underlying the pathogenesis and pathophysiology of the condition. Atopy in infancy seems to predict the severity of bronchial hyperresponsiveness in later childhood. Genetic predisposition, allergen exposure and contributory factors combine to set the clinical picture. Early sensitization to ingested or inhaled allergens accelerates development of allergic asthma. In children, the activity of inflammation can be assessed by estimation of indirect markers.

Asthma↗
PubMed1992

Assessment of histamine release from basophils in whole blood by benzylpenicilloyl poly-L-lysine in penicillin-sensitized patients.

Histamine release from basophil granulocytes in whole blood by benzylpenicilloyl poly-L-lysine (PPL) was investigated in 7 patients with penicillin allergy. All patients presented with systemic immediate hypersensitivity reactions after i.v. administration of penicillin G. Total histamine (of 7 patients) ranged from 27.5 ng/ml to 62.1 ng/ml (mean 43.2 ng/ml). The spontaneous histamine release ranged from 0.15% to 5.1% (mean 1.8%) of the total content. Addition of PPL in various concentrations resulted in values between 0.8 and 9.6%. Although PPL is a reliable allergen for prick- and intradermal testing in the diagnosis of penicillin allergy--demonstrating a histamine liberation in the skin--the in vitro experiment using the same allergen showed no histamine release above 10%. Using a threshold of 5% out of 7 patients, 4 (57%) would show a positive histamine release. Therefore it might indicate that in penicillin allergy a threshold of 5% must be used. In addition, basophils in whole blood and skin mast cells may be activated differently.

Adolescent↗
PubMed1992

Influence of the histamine control on skin reactivity in skin testing.

We investigated the effect of the histamine control (1 mg/ml) on the results of skin prick and intradermal testing with bee and wasp venom. Skin tests were done on the patients' forearms: on the right arm the histamine control and the bee venom dilutions, on the left arm the wasp venom dilutions only, at distances of 4-5 cm. In intradermal testing 11 (9%) of 122 patients showed a positive wheal and flare reaction to the bee venom solution positioned next to the histamine control. The subsequent solutions in higher concentrations did not produce any skin reactions. The results of intradermal testing with bee venom did not occur in intradermal testing with wasp venom or in skin prick testing with both allergens. Our results show clearly that in skin prick tests a distance of 4-5 cm is sufficient to avoid false positive skin reactions. However, using the same distance in intradermal testing showed that histamine affects the skin reactions produced by adjacent allergen solutions. Therefore false positive results may occur.

Bee Venoms↗
PubMed1992

Cross-reactivity with Tagetes in Arnica contact eczema.

A 69-year-old patient, with known mercury and adhesive plaster allergy, developed facial dermatitis within 24 h of contact with arnica (Arnica). Skin testing showed positive reactions to arnica and, among various other plants of the Compositae, also to Tagetes sp. hybr. (marigold). Cross-reactivity between Tagetes and arnica has not previously been described.

Aged↗
PubMedDate not supplied

Association between Helicobacter pylori infection and pancreatic cancer.

PURPOSE: In order to determine whether infection with Helicobacter pylori might be associated with pancreatic adenocarcinoma, we performed a study to compare the H. pylori seroprevalence rate between patients with pancreatic carcinoma and matched control subjects. PATIENTS AND METHODS: Blood samples from 92 patients with histologically confirmed diagnosis of pancreatic adenocarcinoma admitted to our hospital between January 1994 and July 1995 were analyzed for the presence of IgG antibodies against H. pylori by a commercially available enzyme-linked immunosorbent assay. Thirty patients with gastric cancer, 35 patients with colorectal cancer, and 27 healthy volunteers served as controls. In addition to these serological analyses, tumor specimens from 20 patients with pancreatic adenocarcinoma were microscopically investigated for the presence of H. pylori. RESULTS: 65% of pancreatic cancer patients and 69% of those with gastric cancer were found to be seropositive, while only 45% of the other controls tested positive. Statistical analysis revealed no difference in seropositivity between the cohort of patients suffering from pancreatic and gastric cancer. The rate of seropositivity was more prominent, however, in pancreatic cancer patients when compared with those suffering from colorectal cancer combined with normal controls (p = 0.035), with an odds ratio of 2.1 (1.1-4.1). Microscopic evaluation of human pancreatic cancer specimens showed no evidence for the presence of H. pylori. CONCLUSION: Our data suggest an association between H. pylori infection and pancreatic cancer. Despite demonstration of a positive relationship and its physiological plausibility, larger prospective studies are needed to confirm our preliminary findings and to assess H. pylori as a potential carcinogenic risk factor.

Adenocarcinoma↗