Human memory CD4+ T cell response to the major dog allergen Can f 5, prostatic kallikrein.

BACKGROUND: Human CD4+ T cell responses to important animal allergens are still insufficiently understood. OBJECTIVE: To comprehensively characterize in vitro and ex vivo the peripheral blood memory CD4+ T cell responses of subjects with and without allergy to the major dog allergen Can f 5, the only known animal allergen in the kallikrein family of proteins. METHODS: Can f 5-specific memory CD4+ T cell lines (TCLs) were established from the peripheral blood of 12 subjects with and 12 subjects without allergy to Can f 5 and characterized for their functional and phenotypic properties. The results were evaluated with those obtained ex vivo with a novel CD154 enrichment method. The epitopes recognized by the Can f 5-specific TCLs were determined with 72 overlapping 16-mer peptides covering the sequence of the allergen. RESULTS: Can f 5-specific TCLs were obtained at about tenfold higher frequency from allergic than from non-allergic subjects. Functionally, the TCLs of allergic subjects displayed a Th2-biased cytokine phenotype and increased T cell receptor avidity, whereas the TCLs of non-allergic subjects displayed a Th1-/Th0-biased cytokine phenotype and lower TCR avidity. The higher frequency and the Th2 phenotype of Can f 5-specific memory CD4+ T cells in allergic subjects were confirmed by the CD154 enrichment method ex vivo. Six distinct T cell epitope regions of Can f 5 were predominantly recognized by the TCLs from allergic subjects. CONCLUSIONS AND CLINICAL RELEVANCE: Can f 5-specific memory CD4+ T cell responses differ considerably between subjects with and without allergy, as assessed by both in vitro and ex vivo approaches. Peptides containing the dominant T cell epitopes of Can f 5 can be employed for developing peptide-based immunotherapy for dog allergy.

Mammal-derived respiratory lipocalin allergens do not exhibit dendritic cell-activating capacity.

Most mammal-derived respiratory allergens belong to the lipocalin family of proteins. Determinants of their allergenic capacity are still unknown. Innate immune cells, in particular dendritic cells, have been shown to be involved in the allergenicity of some proteins. As recognition by dendritic cells is one of the few plausible mechanisms for the allergenicity of proteins, we wanted to investigate their role in the allergenicity of lipocalin allergens. Therefore, we first incubated human monocyte-derived dendritic cells with immunologically functional recombinant allergens mouse Mus m 1, dog Can f 1 and 2, cow Bos d 2, horse Equ c 1 and natural Bos d 2. Then, the surface marker expression and cytokine production of dendritic cells and their capacity to promote T cell proliferation and Th2 immune deviation in naïve CD4(+) T cells were examined in vitro. We found that near to endotoxin-free lipocalin allergens had no effect on the activation, allostimulatory capacity or cytokine production of dendritic cells. The dendritic cells could not induce immune deviation in naïve CD4(+) T cells. In contrast, lipopolysaccharide activated the dendritic cells efficiently. However, lipocalin allergens were not able to modify the lipopolysaccharide-induced responses. We conclude that an important group of mammal-derived respiratory allergens, lipocalins, appear not to be able to activate dendritic cells, a major component involved in the allergenicity of some proteins. It is conceivable that this incapacity of lipocalin allergens to arouse innate immunity may be associated with their poor capacity to induce a strong T cell response, verified in several studies.

Mammalian lipocalin allergens--insights into their enigmatic allergenicity.

Most of the important mammal-derived respiratory allergens, as well as a milk allergen and a few insect allergens, belong to the lipocalin protein family. As mammalian lipocalin allergens are found in dander, saliva and urine, they disperse effectively and are widely present in the indoor environments. Initially, lipocalins were characterized as transport proteins for small, principally hydrophobic molecules, but now they are known to be involved in many other biological functions. Although the amino acid identity between lipocalins is generally at the level of 20-30%, it can be considerably higher. Lipocalin allergens do not exhibit any known physicochemical, functional or structural property that would account for their allergenicity, that is, the capacity to induce T-helper type 2 immunity against them. A distinctive feature of mammalian lipocalin allergens is their poor capacity to stimulate the cellular arm of the human or murine immune system. Nevertheless, they induce IgE production in a large proportion of atopic individuals exposed to the allergen source. The poor capacity of mammalian lipocalin allergens to stimulate the cellular immune system does not appear to result from the function of regulatory T cells. Instead, the T cell epitopes of mammalian lipocalin allergens are few and those examined have proved to be suboptimal. Moreover, the frequency of mammalian lipocalin allergen-specific CD4(+) T cells is very low in the peripheral blood. Importantly, recent research suggests that the lipocalin allergen-specific T cell repertoires differ considerably between allergic and healthy subjects. These observations are compatible with our hypothesis that the way CD4(+) T-helper cells recognize the epitopes of mammalian lipocalin allergens may be implicated in their allergenicity. Indeed, as several lipocalins exhibit homologies of 40-60% over species, mammalian lipocalin allergens may be immunologically at the borderline of self and non-self, which would not allow a strong anti-allergenic immune response against them.

Animal-derived lipocalin allergens exhibit immunoglobulin E cross-reactivity.

BACKGROUND: Although knowledge of the IgE cross-reactivity between allergens is important for understanding the mechanisms of allergy, the regulation of the allergic immune response and the development of efficient modes of allergen immunotherapy, the cross-reactivity of animal allergens is poorly known. OBJECTIVE: The aim of this study was to characterize IgE cross-reactivities between lipocalin proteins, including five animal-derived lipocalin allergens and one human endogenous lipocalin, tear lipocalin (TL). METHODS: The recombinant proteins were validated by chromatography and mass spectrometry. The IgE-binding capacity of the allergens was confirmed by IgE. immunoblotting and IgE immunoblot inhibition. IgE ELISA was performed with sera from 42 atopic patients and 21 control subjects. The IgE cross-reactivities between the lipocalin proteins were determined by ELISA inhibition. RESULTS: ELISA inhibition revealed IgE cross-reactivities between Can f 1 and human TL, between Can f 1 and Can f 2, and between Equ c 1 and Mus m 1. Low levels of IgE to human TL were found in the sera of seven dog-allergic patients of whom six were IgE-positive for Can f 1. CONCLUSION: Several lipocalins exhibited IgE cross-reactivity, probably due to the sequential identity of the proteins and also due to similarities in their three-dimensional structures. The clinical significance of the findings needs to be elucidated. Low-level IgE cross-reactivity can play a role in regulating immune response to lipocalin allergens.

A randomised controlled trial on whether a participatory ergonomics intervention could prevent musculoskeletal disorders.

OBJECTIVES: To examine the efficacy of a participatory ergonomics intervention in preventing musculoskeletal disorders among kitchen workers. Participatory ergonomics is commonly recommended to reduce musculoskeletal disorders, but evidence for its effectiveness is sparse. METHODS: A cluster randomised controlled trial among the 504 workers of 119 kitchens in Finland was conducted during 2002-2005. Kitchens were randomised to an intervention (n = 59) and control (n = 60) group. The duration of the intervention that guided the workers to identify strenuous work tasks and to seek solutions for decreasing physical and mental workload, was 11 to 14 months. In total, 402 ergonomic changes were implemented. The main outcome measures were the occurrence of and trouble caused by musculoskeletal pain in seven anatomical sites, local fatigue after work, and sick leave due to musculoskeletal disorders. Individual level data were collected by a questionnaire at baseline and every 3 months during the intervention and 1-year follow-up period. All response rates exceeded 92%. RESULTS: No systematic differences in any outcome variable were found between the intervention and control groups during the intervention or during the 1-year follow-up. CONCLUSIONS: The intervention did not reduce perceived physical work load and no evidence was found for the efficacy of the intervention in preventing musculoskeletal disorders among kitchen workers. It may be that a more comprehensive redesign of work organisation and processes is needed, taking more account of workers' physical and mental resources.

Lipocalins as allergens.

The term allergy refers to clinical conditions caused by an inappropriate immune response to innocuous proteins in genetically predisposed persons. Allergens of animal origin are responsible for a significant proportion of allergies. In recent years, it has become evident that practically all respiratory animal allergens characterized at the molecular level belong to the lipocalin family of proteins. The current list comprises the major allergens of horse, cow, dog, mouse, rat and cockroach as well as beta-lactoglobulin of cow's milk. While the molecular structure of all these allergens is known, far less information is available regarding their immunological characteristics. Knowing the way the immune system recognizes these allergens and reacts to them might, however, be the key for discovering the common denominator of the allergenicity of lipocalins. The human body contains numerous endogenous lipocalins, and the immune system has to adapt to their presence. We have proposed that under these conditions the immune response against the lipocalin allergens which are structurally related to endogenous lipocalins might be the pathway to allergy in genetically predisposed persons. The same might well apply also to other allergens with homologous endogenous counterparts.

cDNA cloning and protein analysis of a bovine dermal allergen with homology to psoriasin.

Immunoscreening of a cDNA library from bovine skin led to isolation of clones coding for an allergen named BDA11. Sequence analysis of the clones revealed that they can encode a protein of 11.6 kDa with a predicted pI of 5.19. Allergenicity of BDA11 was verified by the IgE reactivity in cattle-allergic patients' sera with the recombinant protein produced in Escherichia coli. A biochemically purified native allergen of 11 kDa from bovine dander was identified as BDA11 by peptide sequencing. Homology comparisons showed that BDA11 had a 63.4% amino acid identity with human psoriasin. Psoriasin is a calcium-binding protein expressed in keratinocytes, and it is strongly up-regulated in psoriatic skin. BDA11 also had segments homologous with calcium-binding proteins from three other species.

Tear fluid plasmin activity after excimer laser photorefractive keratectomy.

PURPOSE: Elevated tear fluid plasmin activity may correlate with delayed healing of corneal wounds. The present study was performed to establish the tear fluid plasmin activity after photorefractive keratoablation (PRK). METHODS: Tear fluid aspirated with microcapillaries was subjected to a fluorometric plasmin assay using the 7-amido-4-trifluoromethylcoumarin derivate of the tripeptide H-D-Val-Leu-Lys as substrate. RESULTS: Tear fluid flow, plasmin activity, and flow-corrected plasmin excretion rate in tears (plasmin flux) were determined preoperatively and 1, 2, and 7 days after PRK. The preoperative tear fluid flow was 6.55 microliters/min (median; range, 1.8 to 21.8 microliters/min), plasmin activity was 1.29 IU/l (median; range, 0.6 to 6.9 IU/l), and the excretion of plasmin in tears was 11.7 microIU/min (median; range, 1.6 to 41.5 microIU). A statistically significant decrease in tear fluid plasmin activity was found during the follow-up period on the first (0.6 IU/l; range, 0.6 to 1.7 IU/l, P < 0.01) and second (0.65 IU/l; range, 0.6 to 1.49 IU/l, P < 0.01) postoperative days. On the other hand, significant elevation of both tear fluid flow and plasmin flux values occurred during the first two postoperative days. The median plasmin flux values on days 1, 2, and 7 were 57.35 microIU/min (range, 16 to 540 microIU/min, P < 0.01), 40.0 microIU/min (range, 13.3 to 222.8 microIU/min, P < 0.01), and 10.2 microIU/min (range, 2.2 to 90.7 microIU/min, P > 0.05), respectively. CONCLUSION: The marked elevation of tear fluid flow coincided with the persistence of an epithelial defect. However, because of the acceleration of tear fluid flow, proteolytic activity due to plasmin (IU/l) actually decreases. Consequently, the increased excretion of plasmin in tears (plasmin flux) does not lead to highly elevated plasmin activity, which could inhibit wound healing. It seems to be a natural healing response because all corneas were epithelialized normally by or on day 3.

Differential effect of the alpha2-adrenoceptor antagonist, atipamezole, in limb-placing task and skilled forepaw use following experimental stroke.

PURPOSE: Tbc present study compared tbc effect of chronic administration of the selective alpha2-adrenoceptor antagonist, atipamezole, on performance in behavioral tests that differ in motoric complexity in two experimental stroke models. METHODS: Transient occlusion (120 min) of the middle cerebral artery (MCA) using the intraluminal method was used to produce corticostriatal infarcts and permanent occlusion of distal MCA by electrocoagulation was used to produce cortical infarcts. Chronic atipamezole treatment (1 mg/kg, s.c., once per day) was started 2 days after ischemia induction and continued until the end of the experiment, 35 days after ischemia induction. Behavioral performance of the operated rats was assessed 30 min after drug administration using the limb-placing test and Montoya's staircase test. RESULTS: Atipamezole facilitated spontaneous recovery in the limb-placing task particularly in rats subjected to transient MCA occlusion. The analysis of retrieved pellets in Montoya's staircase test suggests that there is no recovery (Time effect, P > 0.05) in the use of the impaired forelimb (contralateral-to-lesion) following transient MCA occlusion, whereas there was some recovery following permanent MCA occlusion (Time effect, P < 0.001). The impairment was bilateral in rats subjected to transient MCA occlusion. Atipamezole treatment did not affect the use of the impaired forelimb to retrieve pellets following transient MCA occlusion, but there was a tendency to facilitate impaired forelimb use following permanent MCA occlusion (Time*Treatment interaction, P = 0.086). CONCLUSION: Transient occlusion of the MCA produced a severe, long lasting, and bilateral deficit in skilled forelimb use. Permanent occlusion of the distal MCA was associated with less severe impairment, which was alleviated to some extent by administration of atipamezole. This is in contrast to spontaneous recovery and recovery-enhancing effects of atipamezole in the limb-placing test, particularly in the transient MCA occlusion model.

Immunoreactive corticotropin-releasing factor and corticotropin during pregnancy, labor and puerperium.

Concentrations of immunoreactive corticotropin releasing factor (CRF) and corticotropin (ACTH) in the plasma were studied in healthy pregnant women. Concentration of CRF was near the detection limit of the assay (2.5 pmol/l) until the 16th week of pregnancy, increasing thereafter significantly towards term: the mean values (+/- S.E.) at weeks 8-11, 12-15, 16-19, 20-23, 24-27, 28-31, 32-35, and 36-40 were 2.9 +/- 0.42, 2.9 +/- 0.72, 5.2 +/- 1.1, 10.2 +/- 5.8, 14.6 +/- 2.0, 32.8 +/- 4.8, 63.6 +/- 9.2, and 187 +/- 39 pmol/l, respectively. The mean concentration of CRF did not increase during labor, and it decreased rapidly after delivery. On the contrary, the mean plasma level of ACTH increased only slightly during late pregnancy, but during labor the increase was significant. These findings suggest that CRF in maternal circulation is not primarily involved in the regulation of maternal ACTH secretion, and the stress of labor does not increase the release of CRF, which probably originates mainly from the placenta.

Tear fluid cellular fibronectin levels after photorefractive keratectomy.

BACKGROUND: Fibronectin is supposed to have an important role in wound healing. The extradomain A-containing cellular fibronectin (EDAcFn) refers to fibronectin, which instead of being a hepatocyte derived component of blood plasma or body fluids, is produced locally. The present study was undertaken to clarify the possible changes in excretion of EDAcFn in tears following excimer laser photorefractive keratectomy (PRK). METHODS: An immunoassay was used to determine EDAcFn concentrations in human tear fluid samples of 11 eyes after PRK. Tear fluids were collected with scaled microcapillaries preoperatively as well as 1, 2, and 7 days after PRK. The time used to collect a known volume of tears was registered. This was done to estimate the dilution effect related to the hypersecretion of tears after PRK. RESULTS: The mean preoperative tear fluid EDAcFn concentration was 0.28 +/- 0.07 ng/microliter with a wide range (0.05 to 0.63). The tear fluid flow-corrected excretion of EDAcFn was 1.36 +/- 0.35 ng/min (range, 0.145 to 3.50). There was a significant increase in both postoperative tear fluid flow and excretion of EDAcFn on days 1 and 2. The elevation of the mean EDAcFn concentration did not decrease in spite of reflex tearing. The mean excretion of EDAcFn in tears was 28-fold on the first and 17-fold on the second postoperative day. Normal level was reached by day 7. CONCLUSION: There is a rapid increase in excretion of EDAcFn in tears following PRK. This seems to last only as long as an epithelial defect persists. The epithelium of all eyes healed in 3 to 4 days in spite of wide interindividual variations in both tear fluid flow and EDAcFn excretion.

Release of calcitonin gene-related peptide in tears after excimer laser photorefractive keratectomy.

BACKGROUND: Sensory nerves known to affect corneal healing are damaged to a variable degree after photorefractive keratectomy (PRK). To search for nerve-bound factors involved in corneal healing, we monitored tear fluid calcitonin gene-related peptide (CGRP) levels of six human eyes undergoing PRK. METHODS: CGRP concentrations were determined using an immunoassay. RESULTS: Normal human tear fluid contains CGRP. The mean CGRP concentration was slightly increased postoperatively, despite a marked tear fluid hypersecretion. Consequently, an almost ten-fold increase in release of CGRP in tears was observed on days 1 and 2 after PRK. Values measured on day 7 had returned to a normal level. CONCLUSION: The observed postoperative increase in release of CGRP in tears may have an impact on the healing of PRK wounds. Extensive neural damage following deep photoablations may impair healing and should probably be avoided.

Elevation of tear fluid plasmin activity of contact lens wearers studied with a rapid fluorometric assay.

Tear fluid plasmin activities were measured by a fluorometric assay based on a lyophilized kit with the 7-amido-4-trifluoromethylcoumarin derivative of the tripeptidyl H-D-Val-Leu-Lys as substrate. The rapid, sensitive method can detect proteolytic activity in small volume tear fluid samples. Plasmin activity levels (IU/L) measured from the samples were corrected with tear fluid flows (microliters/min), yielding a parameter called plasmin flux (microIU/min). Correction is important when patients show tearing due to irritation. Tear fluid samples were collected from 32 asymptomatic contact lens (CL) wearers and 27 controls. Plasmin activity values (2.7 +/- 0.3 IU/L) of CL wearers were higher (p < 0.00006) than those of the controls (1.6-0.1). Mean plasmin flow was 12.6 +/- 1.5 microliters/min for CL wearers and higher for controls (6.8 +/- 0.5 microliters/min). The difference was not significant (p = 0.063). Plasmin flux values of CL wearers (30.0 +/- 4.1 microIU/min) were conspicuously higher than those of controls (10.2 +/- 0.7 microIU/min, p < 0.00006). We conclude that elevated tear fluid proteolytic activity may be related to pathological changes associated with CL wear.

A rapid fluorometric assay for tear fluid plasmin activity.

A rapid (5- to 10-min), sensitive (detection limit 0.6 IU/L), and moderately specific fluorometric plasmin assay for small volume tear fluid samples was developed. Addition of albumin (up to 0.1% final concentration) to the assay buffer improved the sensitivity of the test so that plasmin activity in healthy controls could be detected. pH in the reaction buffer was 8.0, Michaelis-Menten constant for the substrate, H-D-Val-Leu-Lys.7-amido-4-methyl-coumarin (AMC), was 0.28 mM, and final substrate concentration in the reaction buffer was 1 mM. Intra- and interassay imprecisions were 1.6 and 4.4%, respectively at a plasmin level of 10 IU/L. Tear fluid flow was significantly higher in the patients than in the healthy controls, and this dilatory effect must be considered when using plasmin determination for diagnostic purposes. This effect was counteracted by correcting the plasmin activity values by tear fluid flow. Plasmin flux is plasmin activity (microIU) secreted in units of time (min). This parameter showed highly significant differences between the patients and controls. All patients with microbial keratitis, corrosive trauma, ocular trauma, herpetic infection, and other diseases showed highly significant elevation of plasmin flux compared with controls. The highest plasmin flux values (several hundredfold that of controls) were recorded in patients with severe corneal ulcers. Few patient samples showed some involvement of other proteases, which were not inhibited by aprotinin.

Plasma beta-endorphin, beta-lipotropin and corticotropin in polycystic ovarian disease.

In 9 women with polycystic ovarian disease (PCOD) and in 11 control subjects at the follicular phase of the normal cycle, blood samples were collected at 15-min intervals during a 2 h period of bed rest for the assay of beta-endorphin, beta-lipotropin, corticotropin, cortisol and prolactin. During the study period, the plasma levels of these hormones decreased more significantly in the PCOD than in the control group, suggesting that the PCOD patients had a more significant stress response to the puncture of the vein than the control subjects. The second hour of the study period was considered to represent resting levels of hormones. The mean resting levels (+/- S.E.) of the hormones between the PCOD and control groups, respectively, were as follows: beta-E, 2.0 +/- 0.4 vs. 1.1 +/- 0.1 pmol/l, p less than 0.05; beta-LPH, 3.4 +/- 0.6 vs. 2.1 +/- 0.5 pmol/l, N.S.; corticotropin, 2.0 +/- 0.3 vs. 1.1 +/- 0.5 pmol/l, p less than 0.05; cortisol, 176 +/- 24 vs. 128 +/- 16, N.S.; and prolactin; 3.9 +/- 0.6 vs. 5.6 +/- 1.2 ng/ml, N.S. These results confirm the previous findings on increased circulating levels of beta-E in PCOD. A concomitant increase of the plasma level of corticotropin suggests that the basal secretion of both beta-E and corticotropin from the anterior pituitary gland is increased in women with PCOD.

Corticotropin-releasing hormone in maternal and cord plasma in pre-eclampsia.

The concentration of corticotropin-releasing hormone (CRH) in maternal plasma increases greatly during the last trimester of normal pregnancy. This CRH has been proposed to originate from the placenta. We studied plasma immunoreactive CRH in 46 uncomplicated pregnancies, in 10 pregnant women with chronic hypertension, in 17 women with pregnancy-induced hypertension (PIH) and in 24 women with pre-eclampsia, and correlated it to the levels of corticotropin (ACTH) and cortisol. CRH levels were greatly increased in women with pre-eclampsia, less significantly in women with PIH, while no change was found in pregnant women with chronic hypertension. ACTH levels also were increased in pregnancies with pre-eclampsia or PIH and there was a positive correlation between CRH and ACTH levels. CRH levels in cord venous plasma were significantly increased in pregnancies with pre-eclampsia but cortisol did not show any significant increase. These findings suggest that placental release of CRH into the maternal and fetal circulation is increased in pre-eclampsia.

Pneumococcal bacteriology after pneumococcal otitis media with special reference to pneumococcal antigens.

Fifty-four ears with evidence of pneumococcus (Pn) in the first acute otitis media (AOM) in 38 infants and with prolongation or recurrence of the MEF during the follow-up were observed for 7-22 months for the presence of Pn by culture or of pneumococcal antigen (Pn-ag) by counterimmunoelectrophoresis or latex agglutination methods in their MEFs. During the first three 1-month observation periods, Pn and/or Pn-ags were detected in 24% to 9% of these ears, always of the initial type/group. Later on new Pn types/groups appeared also. In two of the 9 MEFs persisting for greater than or equal to 3 months, initial Pn-ag, with culturable Pn, was repeatedly found but not for longer than 5 months. Of the 12 ears resulting in secretory otitis media (SOM) only one showed initial Pn-ag (and Pn) in the MEF of SOM. Pneumococcal type/group pattern associated with prolongation or recurrence of infection did not differ from that of initial AOM. In another series of 151 SOM ears in 97 children, Pn-ags were detected in 7 MEFs. Four of them grew Pn, each of the corresponding group. Our studies suggest that the persistence of Pn-ags in the middle ear after AOM is limited and their occurrence in the MEFs of SOM is rare. Thus, the role of the persistence of Pn-ags in prolonged, recurrent or secretory otitis media seems questionable.

Branhamella catarrhalis in acute otitis media.

A total of 5217 middle ear fluid (MEF) samples obtained from 1203 children with otitis media, aged 3 months to 6 years, were studied for the presence of Branhamella catarrhalis (Br) between Oct. 1977 and Sept. 1981. Br grew in 10.2% of 3497 MEFs of acute otitis media (AOM), with almost the same frequency in the very first and subsequent attacks. During the first 4 years of life the percentage did not vary much; among older children it seemed to decrease. The overall prevalence of Br in AOM did not change during the study period. Br alone grew in 72.4% of acute MEFs with Br; with other bacteria the respective figure was 82.9% (p less than 0.001). Acute attacks with bilateral Br were found in 22.8% of attacks with Br. In 1720 non-acute MEFs obtained at postacute control visits, Br was isolated in only 7.0%. The proportion of beta-lactamase-producing strains among the 2419 otitis-Br strains tested in two laboratories of the two study regions showed an increase from 27.1% and 21.1% in 1980 to 57.6% and 38.6% in 1983, respectively (p less than 0.001).

Nasal sensitization of dairy farmers to bovine epithelial and urinary antigens.

Nineteen dairy farmers with nasal symptoms associated with working in cowhouses participated in the study. Nasal challenge with bovine epithelial antigen (BEA) and bovine urinary antigen (BUA) was made before and after the indoor feeding season. Nasal challenge made before the indoor feeding season with BEA was positive in five patients and three of them showed positive reaction in nasal challenge also with BUA. After the indoor feeding season the results in nasal challenge with BEA were approximately equal to BEA and four of them showed positive response in nasal challenge to BUA. However, we did not find any significant increase in sensitivity in nasal challenge to BEA or BUA after the indoor feeding season. In addition to these patients, two patients who were excluded from nasal challenge before the indoor feeding season showed positive results in nasal challenge after the indoor feeding season with both BEA and BUA. Our results suggest that BUA in addition to BEA may have significance to nasal symptoms.

Detection of artifacts in monitored trends in intensive care.

In intensive care, decision-making is often based on trend analysis of physiological parameters. Artifact detection is a pre-requisite for interpretation of trends both for clinical and research purposes. In this study, we developed and tested three methods of artifact detection in physiological data (systolic, mean and diastolic artery and pulmonary artery pressures, central venous pressure, and peripheral temperature) using pre-filtered physiological signals (2-min median filtering) from 41 patients after cardiac surgery. These methods were: (1) the Rosner statistic; (2) slope detection with rules; and (3) comparison with a running median (median detection). After tuning the methods using data from 20 randomly chosen patients, the methods were tested using the data from the remaining patients. The results were compared with those obtained by manual identification of artifacts by three senior intensive care unit physicians. Out of an average of 22,480 data points for each variable, the three observers labelled 0.98% (220 data points) as artifacts. The inter-observer agreement was good. The average (range) sensitivity for artifact detection in all variables in the test database was 66% (33-92%) for the Rosner statistic, 64% (24-98%) for slope detection and 72% (41-98%) for median detection. All methods had a high specificity (> or = 94%). Slope detection had the highest mean positive prediction rate (53%; 21-85%). When the performance was measured by the cost function, slope detection and running median performed equally well and were superior to Rosner statistics for systemic arterial and central venous pressure and peripheral temperature. None of the methods produced acceptable results for pulmonary artery pressures. We conclude that median filtering of physiological variables is effective in removing artifacts. In post-operative cardiac surgery patients, the remaining artifacts are difficult to detect among physiological and pathophysiological changes. This makes large databases for tuning artifact algorithms mandatory. Despite these limitations, the performance of running median and slope detection were good in selected physiological variables.