Serum eosinophil granule proteins predict asthma risk in allergic rhinitis.

BACKGROUND: Allergic rhinitis is a common disease, in which some patients will deteriorate or develop asthma. It is important to characterize these patients, thereby offering the possibility for prevention. This study evaluated eosinophil parameters as potential indicators of deteriorating allergic airway disease. METHODS: The subjects of the study included all patients who suffered seasonal allergic rhinitis and had participated in a study 6 years earlier, in which blood eosinophils, serum eosinophil cationic protein (ECP) serum eosinophil peroxidase (EPO), nasal lavage ECP and nasal lavage EPO levels were measured. Patients in the present study were interviewed on occurrence of rhinitis symptoms during the last season, rhinitis outside season, asthma-like symptoms and asthma diagnosis, and were skin-prick tested for common aeroallergens. Eosinophil parameters from the study 6 years earlier were then tested for the ability to predict occurrence of new allergies, worsening of rhinitis and occurrence of asthma. RESULTS: Forty-four patients participated in the study. In four patients seasonal rhinitis symptoms had deteriorated, 10 had experienced perennial rhinitis symptoms, 14 reported asthma-like symptoms and seven had been diagnosed with asthma. Thirteen had developed additional sensitization. Patients developing asthma-like symptoms compared with patients with no such symptoms had significantly higher serum ECP (16.7 microg/l vs 8.2 microg/l; P < or = 0.01) and serum EPO (17.9 microg/l vs 8.8 microg/l; P < or = 0.05). Results were similar, considering patients diagnosed with asthma. Blood eosinophils and nasal lavage parameters were not related to development of asthma and asthma-like symptoms. No eosinophil parameter was related to deterioration of rhinitis or additional sensitization. CONCLUSION: Serum ECP and EPO in patients with seasonal rhinitis demonstrated a high predictive ability for later development of asthma.

Endogenous and exogenous control of ecosystem function: N cycling in headwater streams.

Allochthonous inputs act as resource subsidies to many ecosystems, where they exert strong influences on metabolism and material cycling. At the same time, metabolic theory proposes endogenous thermal control independent of resource supply. To address the relative importance of exogenous and endogenous influences, we quantified spatial and temporal variation in ecosystem metabolism and nitrogen (N) uptake using seasonal releases of 15N as nitrate in six streams differing in riparian-stream interaction and metabolic character. Nitrate removal was quantified using a nutrient spiraling approach based on measurements of downstream decline in 15N flux. Respiration (R) and gross primary production (GPP) were measured with whole-stream diel oxygen budgets. Uptake and metabolism metrics were addressed as z scores relative to site means to assess temporal variation. In open-canopied streams, areal uptake (U; microg N x m(-2) x s(-1)) was closely related to GPP, metabolic rates increased with temperature, and R was accurately predicted by metabolic scaling relationships. In forested streams, N spiraling was not related to GPP; instead, uptake velocity (v(f); mm/s) was closely related to R. In contrast to open-canopied streams, N uptake and metabolic activity were negatively correlated to temperature and poorly described by scaling laws. We contend that streams differ along a gradient of exogenous and endogenous control that relates to the relative influences of resource subsidies and in-stream energetics as determinants of seasonal patterns of metabolism and N cycling. Our research suggests that temporal variation in the propagation of ecological influence between adjacent systems generates phases when ecosystems are alternatively characterized as endogenously and exogenously controlled.

Detection of local mast-cell activity in patients with food hypersensitivity.

BACKGROUND: Mast cells play a central role in many inflammatory diseases and assessment of their activation may be of use to provide objective confirmation of the outcome of food challenge in the diagnosis of food hypersensitivity. However, to date, assessment of mast-cell activation using serum markers has been unsuccessful. OBJECTIVE: The aim of this study was to explore whether locally released tryptase could be detected in stool samples from patients with food hypersensitivity. METHODS: Nine patients (median age, 55 years; range, 26 - 68 years) with food hypersensitivity confirmed by double-blind placebo-controlled food challenge were included in the study. Tryptase concentration was assessed in stool samples collected before and after an open food challenge at home and symptoms were recorded throughout the study. Tryptase concentration was also assessed in stool samples from 16 apparently healthy individuals (median age, 44 years; range, 27 - 72 years). RESULTS: Measurement of fecal tryptase levels in 16 healthy control subjects revealed an upper limit of the normal range (mean + 2 SD of log transformed data) of 10 ng/g. Fecal tryptase levels exceeded 10 ng/g in 7 out of 9 patients in one or more samples obtained during the study. The tryptase levels varied between patients in response to the food challenge and the individual mean levels of tryptase correlated with the corresponding levels of the inflammatory marker eosinophil protein X (rho = 0.7500, P = .02). CONCLUSION: Measurement of tryptase levels in stool samples is feasible using the method described here. Our results revealed elevated concentrations of fecal tryptase in patients with food hypersensitivity. However, several factors, including food exposure, may account for the increase in fecal tryptase and further studies are necessary to elucidate the role of mast cells in food hypersensitivity.

Eosinophil cationic protein alters proteoglycan metabolism in human lung fibroblast cultures.

Eosinophil cationic protein (ECP), a highly basic protein secreted from eosinophilic granulocytes, has been shown to take part in the inflammatory reaction. The involvement of ECP in fibroblast activation was therefore investigated in cell culture. Production of proteoglycans, hyaluronan and collagen in the presence of ECP was measured after incorporation of radioactive precursors and separation into different proteoglycan classes using gel and ion exchange chromatography and hydrophobic interaction chromatography. Proteoglycan accumulation in the cell layer was increased two- to fivefold at an ECP-concentration of 10 micrograms/ml. No effect on collagen, other proteins or hyaluronan was noted. Furthermore, no effect was observed on cell proliferation. The increased proteoglycan accumulation could be inhibited by addition of heparin or of antibodies to ECP. The effect could not be mimicked by the two basic peptides protamine and poly-L-lysine, speaking in favor of specificity. The increase in proteoglycan material was seen exclusively in the intracellular pool. No change of proteoglycans in the medium or the cell surface-associated pool was noted. The increase in the cell layer was accounted for by a two- to fivefold increase in free chains of heparan sulfate and dermatan sulfate. No change was seen in the proteoglycan pattern. No effect on proteoglycan synthesis or on endocytosis was noted. The increased accumulation of polysaccharide was caused by inhibited degradation of glycosaminoglycans. The half-lives of large and small heparan sulfate proteoglycans/glycosaminoglycans and dermatan sulfate proteoglycans/glycosaminoglycans in the cell layer are increased four- to sevenfold. We conclude that ECP inhibits proteoglycan degradation in fibroblasts, which indicates a role for the eosinophil in generation of fibrosis.

Human eosinophil cationic proteins (ECP and EPX) and their suppressive effects on lymphocyte proliferation.

ECP (eosinophil cationic protein) and EPX (eosinophil protein X) are two highly basic proteins contained in the granules of human eosinophils. In this study, the effect of ECP and EPX upon lymphocyte proliferation in vitro has been investigated. Peripheral blood mononuclear cells from normal donors were cultured in medium containing ECP or EPX at concentrations from 10(-10) to 10(-7) M. 3H-Thymidine incorporation in PHA-blasts or MLR-blasts was dose-dependently inhibited by both ECP and EPX. The effect was irreversible and was not due to cytotoxic damage. The suppressive effect of EPX may involve suppressor cells. The effect of ECP and EPX on lymphocyte proliferation at relevant in vivo concentrations suggests a regulatory role for the eosinophil in immunological reactions.

The treatment of breast cancer: II. A 20-year follow-up and reappraisal of the en bloc principle.

This retrospective study of the extended Oregon Series (1940 to 1965) of patients with breast cancer, first reported in 1961, compares the now long-term results of treatment of pathologic stage T2/3 NO breast cancers with intent to cure by the following two en bloc ablative operative procedures of variable extent and completeness: standard radical mastectomy vs ultraradical mastectomy. The extent and completeness of the en bloc procedure are shown again to be critical determinants of local control and survival. The local recurrence rate for standard radical mastectomy is 12.4% (8/70) and for ultraradical mastectomy it is 0% (0/78). Proportionate survival at 20 years for standard radical mastectomy was 59.8% (95% confidence limits, 0.598 +/- 0.14) and for ultraradical mastectomy it was 98.1% (95% confidence limits, 0.981 +/- 0.04).

Icons in surgery.

This company of surgeons, the Pacific Coast Surgical Association, has honored me greatly, and I am grateful. In a turbulent, changing world, as physicians, you are among the most important people on earth. More important, by far, than any technologic aspect of your craft, is your character. As the pen is mightier than the sword, your beliefs and values are the sustaining force that will guide you in troubled times. Icons are Everyman's "pointers of the way" in meeting the challenges of tomorrow.

Evaluation of injury mechanism as a criterion in trauma triage.

Triage of potentially injured patients to the appropriate trauma hospital was carried out using mechanism of injury as a triage criterion rather than physiologic changes (trauma score). Injury mechanism includes field evidence of high energy transfer, such as falls of more than 15 feet, automobile accidents with structural intrusion, extrication difficulties, passenger ejection, or death at the scene. Evaluation of triage decisions for a 3 month period in 631 patients showed an overtriage rate of 14 to 43 percent. Using the trauma score alone would have missed significant injuries in at least 8 to 36 percent of these patients using the injury severity score or clinical criteria. Methods of evaluation of overtriage and undertriage are presented, but accepted standards for these must be addressed in each trauma system. Injury mechanism as a primary trauma triage criterion is an acceptable means of identification of potential injury for transport to a trauma facility.

Hyperparathyroidism and pregnancy.

Six pregnancies occurring in four mothers with hyperparathyroidism have been presented. Four of the pregnancies were completed without therapy; in two, parathyroidectomy was performed. The outcome of each of the pregnancies was satisfactory. The 49 cases previously reported are reviewed. This experience demonstrates that parathyroidectomy is indicated if the mother has symptomatic hypercalcemia, and it can be safely performed during the second trimester. Pregnant women with mild, asymptomatic hypercalcemia may be followed nonoperatively during pregnancy with satisfactory outcome to both the mother and fetus.

Changes in inflammatory markers following treatment of acute exacerbations of obstructive pulmonary disease.

The aim ofthe study was to investigate changes in inflammatory markers following emergency treatment of obstructive pulmonary disease. The study comprised 43 patients. After acute treatment, they were given either 30 mg of prednisolone p.o. or 1600 microg of inhaled budeson de daily for 1 week. Over the following 3 weeks, all the patients were given 1600 microg of inhaled budesonide daily. Blood samples for measurements of eosinophil cationic protein (S-ECP), eosinophil peroxidase (S-EPO), total eos nophil count (B-Eos), myeloperoxidase (S-MPO) and human neutrophil lipocaline (HNL) were taken and spirometry was performed before emergency treatment and after 1 and 4 weeks. There was no difference in the improvement in forced expiratory volume in 1 sec (FEV1) between patients given prednisolone or budesonide. Patients with an improvement in FEV1 of >20% of baseline after 1 and 4 weeks displayed a larger decrease in eosinophil markers. The correlation between deltaFEV1 and deltaS-ECP was r= -0.37, P < 0.05, deltaS-EPO -0.40, P < 0.01 and deltaB-Eos -0.44, P < 0.01, after 4 weeks. This correlation was highly significant in patients who had smoked < or = 5 pack-years, while the correlation was not significant in patients with a longer smoking history and chronic airflow limitation (best FEV <80% of predicted). We conclude that the change in eosinophil markers is correlated to the improvement in lung function in non-smokers or short-term smokers following the emergency treatment of obstructive pulmonary disease. This study indicates that following eosinophil markers is more useful in patients with asthma than patients with COPD.

Inflammatory markers in acute exacerbations of obstructive pulmonary disease: predictive value in relation to smoking history.

The aim of this study was to investigate the relationship between the effect of emergency treatment and inflammatory markers in patients with acute exacerbations of obstructive pulmonary disease, especially with respect to smoking history. We investigated 50 unselected patients with acute bronchial obstruction. Blood, urine and sputum samples were taken and analysed for eosinophil and neutrophil markers. The patients were observed for at least 2 h and recordings of forced expiratory volume in 1 s (FEV1) were taken. They were re-examined after 1 and 4 weeks. The absolute levels of inflammatory markers did not differ significantly between non- or short-term smokers (< or = 5 pack-years) and long-term smokers (> 5 pack-years) with the exception of myeloperoxidase in serum (S-MPO), which was higher in long-term smokers. The patients with higher levels of eosinophil markers before emergency treatment experienced a greater improvement in lung function. In non- or short-term smokers this relationship was found in blood and urine, whereas in long-term smokers it was seen in sputum. No correlation was found between neutrophil markers and changes in lung function. We conclude that patients with obstructive pulmonary disease with acute exacerbations and high levels of eosinophil markers respond well to treatment.

Nitrogen retention in headwater streams: the influence of groundwater-surface water exchange.

Groundwater-surface water (GW-SW) interaction lengthens hydraulic residence times, increases contact between solutes and biologically active surfaces, and often creates a gradient of redox conditions conducive to an array of biogeochemical processes. As such, the interaction of hydraulic patterns and biogeochemical activity is suspected to be an important determinant of elemental spiraling in streams. Hydrologic interactions may be particularly important in headwater streams, where the extent of the GW-SW mixing environment (i.e., hyporheic zone) is proportionately greater than in larger streams. From our current understanding of stream ecosystem function, we discuss nitrogen (N) spiraling, present a conceptual model of N retention in streams, and use both of these issues to generate specific research questions and testable hypotheses regarding N dynamics in streams.

Update in allergy testing in childhood asthma: how do you know whether you are successfully controlling the patient's inflammation?

The levels of serum eosinophil cationic protein (ECP) in asthmatic patients have been shown to be increased in acute and undertreated asthma as a result of inflammation. ECP is released during in vitro clotting of peripheral blood. The exposure of the atopic individual to an offending allergen stimulates the activation of the blood eosinophils and their release of ECP into serum. Serum ECP levels reflect avoidance of the allergen, and successful treatment of asthma inflammation with corticosteroids cause a reduction of the inflammation in the lung. When individual patients with asthma are followed, the level of serum ECP can be used (1) as an early indicator of the degree of inflammation, (2) for monitoring the efficacy of corticosteroid therapy, and (3) for possible noncompliance with treatment.