Psychological symptomatology following parental death in a predominantly minority sample of children and adolescents

BACKGROUND: Allergenic crossreactivity of pollen and foods due to the antigeneic similarity of oligopeptides is a well established clinical phenomenon. OBJECTIVE: To determine the immunopathological relevance of antigen presentation, we analysed the HLA class-II genotype of patients with either pollen allergy or pollen associated food allergy. METHODS: One hundred and twenty patients with pollen allergy and 80 patients with pollen associated food allergy were evaluated by skin- prick tests, RAST, and HLA class-II genotyping. The control population comprised 4251 healthy blood and bone marrow donors. RESULTS: Monovalent pollen allergy was observed in 57% (n=68) of patients with pollinosis (57x grass pollen, 11x birch pollen), but only in 15% (n=12) of patients with food allergy (9x grass pollen, 3x birch pollen). Hazelnut (71%), almond (65%), walnut (44%) and apple (41%) were the most common food allergens and frequently associated with birch pollen allergy. Grass pollen allergy was associated with an increased frequency of HLA-DQB1*0301 (RR=2.3; EF=0.4; P=0.0016) when compared with the control population. HLA-DRB *08 conferred a sixfold higher risk for peanut allergy (EF=0.3; P=0.0013) and -DRB1*12 a 13-fold higher risk for carrot allergy (EF=0.3; P<0.000001). The differences on allele frequencies detected among patients with food allergies diminished or turned statistically insignificant when their genotypes were directly compared to those of patients with the corresponding pollen allergies. This was found in the case of birch pollen associated hazel nut allergy for the extended haplotype HLA-DRB1*01, -DQA1*0101, -DQB1*0501 as well as in grass pollen associated peanut allergy for HLA-DRB1*08 (from RR=6, P=0.0013 to insignificant) and in birch pollen associated carrot allergy for HLA-DRB1*12 (from RR=13, P < 0.000001 to insignificant). CONCLUSION: We were able to identify HLA class-II alleles associated with some allergies thus indicating that these alleles might confer susceptibility to the respective allergens. Similarities at the level of the HLA class-II genotype parallel the empirical finding of distinct cross-reactivity patterns thus complementing investigations of IgE specificities. Our observations provide evidence for the major importance of antigen presentation on the manifestation of distinct crossreactivity patterns.     

Human group C rotavirus in children with diarrhea in the Federal District, Brazil

BACKGROUND: A family history of atopy is a poor predictor of sensitization to inhalant allergens and allergic disease during childhood. We recently identified early sensitization to food allergens, especially hen's egg, as a valuable predictor of subsequent sensitization to inhalant allergens. OBJECTIVE: (1) Whether prediction will be improved by in vitro allergy tests at 1 year of age in combination with family history and medical history data. (2) Comparison with the capacities of in vitro tests to predict sensitization to aeroallergens. METHODS: Of an observational birth cohort study (MAS) 49 children who were sensitized to inhalant allergens at 5 years of age and 116 non-sensitized controls were included in the present study. For the prediction of sensitization to inhalant allergens the following prognostic factors were evaluated: atopic family history (FH), atopic dermatitis (AD) during the first year of life, two in vitro allergy tests for specific IgE to common food allergens at 1 year of age (fx5 [Pharmacia] and single allergen specific tests (sIgE) for four allergens) and 'high' total serum IgE, defined by three different cut off points. RESULTS: The combination of medical history data and laboratory tests resulted in the best predictive discrimination. The positive predictive values (PPV) were higher if sensitization to food was detected by single allergen specific tests (PPV: 66%/75%/100% corresponding to the three evaluated risk groups) than by the qualitative fx5 (PPV: 46%/65%/100%). The negative predictive values were equal for both tests (69 and 92% for the two low risk groups). High total serum IgE had low predictive capacity. CONCLUSION: During infancy the prediction of sensitization to inhalant allergens should be based on medical history data and allergy tests determining sensitization to food allergens. The in vitro tests improve the predictive discrimination, but the individual risk profile of the child must be considered for a reliable and valid prediction.     

Beneficial effect of alpha-blocker on hemorheology in patients with essential hypertension

BACKGROUND: An increased prevalence of allergic diseases and atopic sensitization as assessed by skin-prick testing in children in West compared with East Germany has been reported. OBJECTIVES: This study was designed to evaluate whether such a difference is also present in adults, and if this can be shown when using a serological test for allergic sensitization. METHODS: Two large samples representative for all adults between 25 and 69 years of age were drawn in West (1991, n = 5313) and East Germany (1992, n = 2617). A serological test screening for IgE-antibodies to common aeroallergens (SX1) was performed. A questionnaire was used to assess the presence of clinical respiratory allergy, known possible risk factors for allergies and confounding variables. RESULTS: Allergic sensitization decreased with age. Significantly more subjects < 45 years of age had a positive allergy test in West as compared to East Germany. The prevalence of clinical allergy was also higher in West Germany. This difference was significant in younger adults and was independent of other risk factors identified. These additional risk factors encompassed younger age, higher educational level, male sex, and living in a community with more than 100,000 inhabitants. CONCLUSION: Sensitization to common aeroallergens as determined by a multiple allergen RAST test in adults below 45 years of age living in West Germany is increased compared to East Germany. This increase cannot be explained by genetic differences and is similar to the West to East decreasing gradient in allergies reported from studies in children employing skin-prick tests.     

Alternaria as a major allergen for asthma in children raised in a desert environment

The relationships of asthma and allergic rhinitis with individual immediate skin test responses were examined for preferential associations and for changes with age in children raised in a semiarid environment. Prevalence of physician-diagnosed asthma was 9.8% at age 6 (n = 948) and 15.5% at age 11 (n = 895). Immediate skin test responses to Bermuda grass were the most prevalent among children with allergic rhinitis and control subjects, whereas responses to the mold, Altenaria alternata, were the most prevalent among asthmatics. Skin test responses for crude house dust, Dermatophagoides farinae, and cat had low prevalences in all groups. By logistic regression, Alternaria was the only allergen independently associated with increased risk for asthma at both ages 6 and 11. Allergic rhinitis showed independent association with sensitization to Bermuda grass and mulberry tree pollen at age 11 but did not show an independent relation to any single allergen at age 6. Logistic regression further revealed that persistent asthma (diagnosed before age 6) was independently associated with Alternaria skin tests at both ages 6 and 11, whereas new asthma (diagnosed after age 6) was associated with Alternaria skin tests at age 6 but not at age 11. We conclude that Alternaria is the major allergen associated with the development of asthma in children raised in a semiarid environment and that skin test responses at age 6 are more closely linked to asthma than those at age 11.     

Effects of IL-4 and IL-13 on total and allergen specific IgE production by cultured PBMC from allergic patients determined with recombinant pollen allergens

BACKGROUND: Interleukin (IL)-4 and IL-13 have been shown to be potent switch factors for IgE synthesis in human B cells. OBJECTIVE: In this study we investigated the effects of recombinant human IL-4 and IL-13 on total and allergen specific IgE synthesis by peripheral blood mononuclear cells (PBMC) from pollen allergic patients and healthy control individuals. METHODS: Peripheral blood mononuclear cells (PBMC) from allergic patients were investigated for their capacity to produce allergen specific IgE in vitro. Total protein extracts from birch pollen and timothy grass pollen as well as purified recombinant birch pollen allergens, Bet v I, birch profilin (Bet v II) and recombinant timothy grass pollen allergens, Phl p I, Phl p II, and Phl p V were used to measure specific IgE-antibody synthesis in cell culture supernatants by IgE-immunoblot and ELISA. RESULTS: PBMC obtained from allergic patients spontaneously secreted allergen specific IgE in the culture supernatants. Addition of Interleukin 4, Interleukin 13 and anti-CD40 antibody to the cultures alone or in combinations significantly induced total IgE production whereas allergen specific IgE production was not affected. CONCLUSION: Our results indicate that the peripheral blood of allergic individuals contains long lived allergen specific B cells which have already switched to IgE production and which are not sensitive to IL-4 and IL-13 treatment. These results may have implications on attempts to use cytokines or cytokine antagonists in therapy of Type I allergy.     

Specific V beta T cell subsets are associated with cat and birch pollen allergy in humans

Cognate interaction between TCRs and MHC class II molecules plays an important role in initiating the allergen-specific immune response. Therefore, we analyzed the TCR distribution of human PBLs of 56 atopic and nonatopic (NA) individuals, including 4 monozygotic twin pairs, from two extended and four nuclear families. The expression of 23 V beta and 3 V alpha elements was analyzed. The blood samples of symptomatic birch pollen-sensitized individuals that were taken < or = 6 wk after the birch pollen season (n = 8) showed a significantly higher frequency of V beta 16.1+ and V beta 20.1+ T cells compared with the blood samples of birch pollen-sensitized individuals that were obtained out of allergen season (n = 10) or from NA individuals (p < 0.0005 and p < 0.0001, respectively). Allergen-specific lymphocyte proliferation was detected in the allergic individuals, and the distribution of V beta 16.1+ and V beta 20.1+ T cells returned to normal levels after the pollen season. The frequency of these V beta-expressing T cells correlated with the levels of allergen-specific IgE Abs. In addition, cat-sensitized individuals (n = 8) showed a significantly higher frequency of V beta 17.1-expressing T cells than did NA individuals (p < 0.005). Our results indicate restricted TCR-V beta gene usage in cat and birch pollen allergies; we suggest that both genetic and environmental factors contribute to TCR-V beta gene expression and to the development of a specific T cell response.     

Atopy and allergic disorders among adults in Tartu, Estonia compared with Uppsala, Sweden

BACKGROUND: Recent studies in children and adults indicate that the prevalence of atopy and allergic disorders is lower in previously socialist countries in Eastern Europe compared with countries with a market economy while revealed risk factors are similar. OBJECTIVES: To estimate the prevalence of atopy among adults in Tartu, Estonia and to compare the prevalence of risk factors for atopy and allergic respiratory diseases in Estonia and Sweden. METHODS: As a part of cross-sectional study-European Community Respiratory Health Survey-random samples of 20-44 year olds (n = 351 in Tartu and n = 470 in Uppsala) and persons of the same age with asthma like symptoms or on current asthma medication according to a postal questionnaire (n = 95 in Tartu and n = 201 in Uppsala) were interviewed and circulating IgE antibodies were measured. RESULTS: The prevalence of atopy was 19% in Tartu and 32% in Uppsala (P < 0.001). The prevalence of sensitization to pollen was twice lower (11.5 vs 23.2; P<0.001) and the prevalence of pollen associated asthma symptoms was four times lower (1.7 vs 6.8; P<0.001) in Tartu than in Uppsala while sensitization to pollen was an equally large risk factor for asthma in both centres. Age was inversely related to cat and pollen associated symptoms of rhinoconjunctivitis in Uppsala (OR 0.6 and 0.7, respectively, P < 0.05) but not in Tartu. CONCLUSIONS: The prevalence of atopy was lower in Tartu, Estonia than in Uppsala Sweden. Perception of allergic disorders seemed to be lower in Tartu than in Uppsala. Age did not influence the prevalence of atopy nor allergic disorders in Tartu, while in Uppsala age was inversely related to clinical allergy. This could suggest a cohort effect underlying the increasing prevalence of allergy in Western Europe.     

Plasma lipoprotein(a) is not a predictor for restenosis after elective high-pressure coronary stenting

BACKGROUND: Preceding mucosal response to one allergen leads to the priming of the nasal mucosal response to another allergen. This study aimed to determine whether environmental allergens, especially ubiquitous animal dander, can induce nasal priming. METHODS: We investigated 26 grass-pollen-allergic subjects with additional sensitization to other aeroallergens. We performed continuous allergen challenge for 2 h with 1500 Dactylis glomerata pollen/m3 in the Vienna challenge chamber. The nasal flow at 150 Pa was examined, and subjective scores were obtained every 15 min. Statistical analysis was calculated from the area under curve of nasal flow reduction by Student's t-test and the Mann-Whitney U-test. Alpha was 0.05. RESULTS: In subjects with positive cat-dander RAST (class of > or = 3), besides grass-pollen allergy, the specific nasal allergic reaction to Dactylis challenge was significantly pronounced (P < 0.01), and an earlier onset of reaction was evident. The same results were obtained with additional sensitization to dog dander (P < 0.05). Concomitant sensitization to mugwort also led to escalating symptoms (P < 0.05). CONCLUSIONS: These results indicate that a specific nasal allergic reaction is augmented by environmental priming caused by ubiquitous animal dander and possibly is influenced by the daily use of spices.     

Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis. ECP and EPX levels are not related to bronchial hyperreactivity

BACKGROUND: Symptoms of allergic asthma are triggered by allergen exposure inducing allergic inflammation and hyperreactivity of the bronchi. OBJECTIVES: To investigate the possible relationship between clinical symptoms and signs of asthma, i.e. bronchial variability as measured by peak expiatory flow rate (PEFR), bronchial hyperreactivity (BHR) and mediators of allergic inflammation. METHODS: Twenty-eight children with pollinosis, but no obvious history of asthma, were studied at three occasions, i.e. before, during and after (autumn) the birch pollen season. Twelve children sensitive to birch pollen were considered as the case group. Sixteen children, who were only clinically sensitive to grass pollen, served as controls. Subjective symptoms of asthma were recorded by visual analogue scale, BHR was estimated by methacholine bronchial provocation tests, bronchial variability PEFR and circulating mediators of inflammation, i.e. eosinophil cationic protein, eosinophil protein X, myeloperoxidase and tryptase in serum. RESULTS: Bronchial hyperreactivity and by PEFR was more pronounced after than during the season (P < 0.01), whereas eosinophil mediators and the peak expiratory flow rate increased during the season (P < 0.05). Except for between PEFR variability and BHR in the autumn (r = 0.45; P = 0.014), no correlations were found. However, in the autumn, the majority of children were still hyperreactive in the bronchi and showed PEFR variability but the levels of eosinophil mediators in serum had returned to normal levels. CONCLUSION: Signs and symptoms of asthma did not correlate with serum levels of mediators of allergic inflammation. Bronchial hyperreactivity and PEFR variability persisted after the pollen season when signs of bronchial inflammation had disappeared. We hypothesize that eosinophil mediators and other markers of allergic inflammation disappear after the late-phase reaction, whereas BHR persists. This would explain the lack of correlation between the levels of eosinophil mediators in serum and symptoms of asthma and BHR.     

The development of atopic sensitization in Estonian infants

In a prospective study, 251 infants were followed from birth up to 12 months of age, recording manifestations of allergy by questionnaires at 3, 6, 9 and 12 months and by clinical examinations at 6 and/or 12 months. Blood samples were obtained at birth and at 6 and 12 months and analysed for serum IgE levels. The children were skin-prick tested with foods at 6 and 12 months of age and with inhalant allergens at 12 months. Blood samples from SPT-positive individuals and controls were analysed for the presence of IgE antibodies to common inhalant allergens and their cord sera for the presence of IgE antibodies to cow's milk and egg. Twelve infants (7%) were sensitized against foods [3 to cow's milk (CM) and 9 to egg white (EW)] at 6 months and 11 (5%) (2 to CM and 9 to EW) at 12 months. Seventeen infants (7%) had IgE antibodies against inhalant allergens at 6 and/or 12 months, as determined by either SPT and/or the demonstration of circulating IgE antibodies. Out of 30 children with positive SPT and/or circulating IgE antibodies against foods and inhalant allergens at any age, 6 had atopic dermatitis, 4 gastrointestinal food allergy, 1 urticaria and 4 probable allergy, while 15 had no clinical manifestation of allergy. Immunoglobulin E antibodies against Ascaris were detected in 17% of the infants with S-IgE levels > 20 kU/l. The study indicates that the incidence of sensitization and manifestations of allergic disease is similar among Estonian and Scandinavian infants during the first year of life. Given earlier findings indicating a significantly higher prevalence of atopic disease in Scandinavian school-children relative to their counterparts in Eastern Europe, the present study suggests that the key events which determine disease expression do not occur exclusively during the first year of life.     

Helicobacter pylori and intestinal metaplasia

Gastric carcinoma of the intestinal type is assumed to develop from precancerous gastric lesions. It is now widely accepted that Helicobacter pylori (HP) infection causes chronic gastritis and, after a period of time, intestinal metaplasia (IM). It was suggested that these gastric lesions may evolve into gastric carcinoma after a lengthy latency period. HP seropositivity is high in Turkey at early ages. This may explain the high incidence of gastric carcinoma in this geographic region. In this study, we examine the relationship between HP and IM in endoscopic gastric biopsy specimens. We examined 840 biopsies taken from 210 patients. HP positivity and the presence of IM were examined in these specimens by histopathologic methods. HP positivity was also determined by CLO testing. HP was positive in 156 of the 210 patients examined (74.3%). The distribution of HP seropositivity did not differ between age groups (p > 0.05). IM was present in 101 patients in the entire study group (48%). Among the 156 HP-positive patients, the rate of IM was 44.8% (n = 70). The rate of IM among the 54 HP-negative patients was 57.4% (n = 31), which was not statistically significant (p > 0.05). IM positivity has been shown to increase in older age, which was statistically significant (p < 0.001). We were not able to show a relationship between HP seropositivity and IM. Increased HP seropositivity at an early age is a common risk factor in our population. We must consider other factors that may contribute to the increased rate of IM in older age groups.     

Innate resistance to infection by intracellular bacterial pathogens differs in mice selected for maximal or minimal acute inflammatory response

PURPOSE: The mechanisms that underlie the clinical efficacy of melanoma vaccines are not well understood. We hypothesized that the type and strength of the immune response generated by CancerVax (John Wayne Cancer Institute, Santa Monica, CA), a polyvalent melanoma cell vaccine (PMCV), might be correlated with its effect on overall survival (OS). PATIENTS AND METHODS: Seventy-seven patients began PMCV therapy after complete surgical resection of distant metastatic melanoma. During the first two treatments, PMCV was administered with bacille Calmette-Guerin (BCG). Blood was drawn at 0, 2, 4, 8, and 12 weeks to measure serum titers of immunoglobulin G (IgG) and IgM antibodies against a tumor-associated 90-kd glycoprotein antigen (TA90) expressed on most melanoma cells, including those of PMCV. Cellular immune response to PMCV was assessed by delayed-type hypersensitivity (DTH). General immune competence was assessed by skin tests to purified protein derivative (PPD), mumps, and candida. RESULTS: Median follow-up time was 31.5 months. Within the first 12 weeks of PMCV immunotherapy, there was a significant increase in the anti-TA90 IgM (P=.0001) and IgG titers (P=.0001), and in the DTH response to PMCV (P=.0001). Univariate analysis showed that high anti-TA90 IgM titer and strong PMCV-DTH were associated with improved survival (P=.051 and .0173, respectively), whereas elevated anti-TA90 IgG was correlated with decreased survival (P=.0119). Multivariate analysis considering clinical variables and PMCV immune responses identified anti-TA90 IgM, anti-TA90 IgG, and PMCV-DTH as significant independent variables influencing survival following PMCV immunotherapy (P=.0342, .0105, and .0082, respectively). These responses to PMCV were not correlated with immune responses to BCG and therefore were not a manifestation of general immune competence for responses to unrelated antigens. The median survival time and 5-year survival rate were more than 76 months and 75%, respectively, if both anti-TA90 IgM and PMCV-DTH responses were strong (> or = 800 and > or = 7 mm, respectively; n=29); 32 months and 36%, respectively, if only one response was strong (n=35); and 19 months and 8%, respectively, if neither was strong (n=13) (P < .0001). CONCLUSION: PMCV induces both humoral and cell-mediated immune responses to melanoma-associated tumor antigens, the type and strength of which appear to be directly related to its therapeutic efficacy.     

Prevalence of Borrelia burgdorferi serum antibodies in 651 patients with predominantly neurologic diseases

An analysis was undertaken to the records of 651 patients (median age 51 years, range 1-91; 334 male and 317 female patients), who were admitted for various reasons to the department of neurology and psychosomatics of the county hospital in Villach (K?rnten, Austria), over the period of one year. The clinical diagnoses were mostly neurological and psychiatric (n = 599), involving 25 different conditions. Other diagnoses (n = 52) comprised a group of 13 various conditions. Sera of all these patients were tested for antibodies to Borrelia burgdorferi. Overall seropositivity was 37.8%. Seropositivity increased significantly with age (p < 0.01). Seroprevalence exceeded 40% in patients with meningitis, paresis of the cranial nerves, cervical syndrome, pareses and sponylitis. The erythrocyte sedimentation rate (ESR) was raised in 37.9% of cases which was not related to seropositivity. ESR was significantly increased in patients with lumbago (p < 0.01) and with arthritis (p < 0.05). Antibiotics and dosages used were recorded in 164 cases. All these cases improved after therapy. Of 81 patients with a history of tick bite, 43 (53%) were seropositive. This is a significantly higher incidence than that of patients without tick bites (p < 0.01). The retrospective evaluation of patients' records showed that anamnestic and clinical findings alone do not suffice to establish the specific diagnosis of Lyme borreliosis and, hence, do not provide the indication of appropriate therapy. Furthermore, the mere demonstration of serum antibodies to Borrelia burgdorferi does not give information on the current state of infection. In case of a suspected Borrelia burgdorferi infection confirmatory tests are needed.(ABSTRACT TRUNCATED AT 250 WORDS)     

The guinea pig as a model for the study of maternal immunization against respiratory syncytial virus infections in infancy

Maternal immunization might protect infants from severe disease due to respiratory syncytial virus (RSV). Guinea pigs are susceptible to infections with RSV and transfer antibodies to their offspring prenatally. Pregnant guinea pigs were immunized by infection with RSV and their offspring were challenged intranasally with RSV. Pulmonary viral replication was compared among the pups born to immunized mothers (group A) and the pups from nonimmune mothers (group B) in two studies. Mean (+/-SD) log10 virus titers were, in study 1, group A, 2.3 +/- 0.8 pfu/g of lung (n = 10); group B, 3.6 +/- 1.5 pfu/g (n = 13) (P = .0058); and study 2, group A, < 1.69 pfu/g (n = 8); group B, 3.4 +/- 0.9 pfu/g (n = 6) (P = .0002). Thus, immunization of pregnant guinea pigs resulted in a significant reduction in viral replication in the lungs of their offspring. Guinea pigs should be useful for the study of maternal immunization against RSV.     

Breast feeding for prevention of viral acute respiratory diseases in infants]

The incidence of acute viral respiratory diseases (confirmed by immunofluorescence test) was compared in a group of 159 infants aged 0-9 months breast-fed at least once daily and in a group of 608 infants of similar age and hospitalization duration receiving only artificial food. The incidence was significantly lower in breast-fed infants (p = 0.00057), especially in the first trimester of life (p = 0.00039). This was valid of all RSV infections (p = 0.01854) and parainfluenza type 4 virus infections (p = 0.0846). The antibody level against parainfluenza type 1 and 3 (HI) and against RSV in IgA class (ELISA) was compared with that in mother's milk and serum. No significant correlation was found for parainfluenza type 1 antibodies (r = 0.159) and 3 (r = 0.025), while for RSV the correlation was positive and statistically significant though rather low (r = 0.234). No significant correlation was found between milk antibody levels and the incidence of acute viral respiratory infections. Breast-feeding showed a significant influence on the lower incidence of these infections, particularly in the first trimester of life. It seems that this was associated with a non-specific mechanism rather than with the milk levels of specific antibodies.     

Appearance of granulocyte-macrophage colony-stimulating factor activity at allergen-challenged cutaneous late-phase reaction sites

The cytokines IL-3 and granulocyte-macrophage CSF (GM-CSF) activate and/or prime monocytes, basophils, and eosinophils for a number of proinflammatory events in vitro. It was hypothesized that IL-3 and GM-CSF might also participate in the local inflammatory cascades that occur at cutaneous blister sites after Ag challenge in vivo. The M-07e megakaryocytic leukemia cell line, which proliferates in response to IL-3 or GM-CSF, was used to determine whether these cytokines were present in fluids derived after Ag challenge in the cutaneous blister chamber model. Fluids from blister chambers after either Ag (timothy grass, orchard grass, or ragweed) or vehicle control challenge were collected hourly for 12 h from nine patients with allergic rhinitis. Cytokine (IL-3/GM-CSF) activity was modestly elevated at 4 h after Ag challenge compared to control with the median of maximal proliferation 4% (range, 2 to 22%) vs 2% (range, 1 to 14%), respectively (Ag vs control, p < 0.03). Activity peaked at 7 h (Ag = 10%, range 1 to 12%, vs control = 1%, range 1 to 9%, p < 0.02) and then steadily declined. No increase in cytokine activity over control was seen in Ag-challenged nonatopics (n = 5, p = NS), indicating that release did not result from a nonspecific effect of the Ag solution. Neutralization of cytokine bioactivity in pooled late phase reaction (LPR) fluids from h 4 to 12 (n = 5) with anti-IL-3, anti-GM-CSF, or both antisera revealed that the majority of the activity was GM-CSF. To better quantify cytokine levels, pooled LPR fluids prepared from an additional 11 subjects were concentration-dialyzed (10x) and tested for cytokine activity. Pooled fluids from Ag-challenged sites contained a median of 625 pg/ml (range, 30 to 1250 pg/ml) GM-CSF equivalents, whereas those from the vehicle control-challenged sites contained a median 30 pg/ml (range, 30 to 300 pg/ml) GM-CSF equivalents (p < 0.004 Ag vs control groups, n = 11). Concentrated fluid from Ag- and control-challenged sites in two nonatopic subjects contained < 10 pg/ml cytokine activity. To evaluate the IL-3 and GM-CSF activity with a separate technique, ELISA were performed on separately pooled blister fluids from six atopic subjects. Although no IL-3 activity was detected after Ag challenge in these six subjects, all of them demonstrated levels of GM-CSF at Ag-challenged sites comparable to that found in the bioassay.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chemotherapy as a part of each treatment fraction in a twice-a-day hyperfractionated schedule: a new chemoradiotherapy approach for advanced head and neck cancer

In allergic asthma, there is convincing evidence that changes in eosinophil and lymphocyte state of activation in blood may reflect disease activity. We evaluated whether simple blood eosinophil or lymphocyte counts in atopic children with asthma could reflect the degree of allergic sensitization. Seventy-six asthmatic children, sensitized to house dust mites (HDM), in stable conditions at the time of the study, and 53 sex- and age-matched controls (CTR) were studied. As compared to CTR, allergic patients showed higher eosinophil numbers and percentages (p < 0.001) but similar lymphocyte numbers and proportions (p > 0.1). Both in CTR and in allergic patients, eosinophil counts did not correlate with lymphocyte counts (p > 0.05; each comparison) but positive correlations were observed between eosinophil numbers and percentages and paper radio immunosorbent test (PRIST) levels or radio-allergo sorbent test (RAST) classes (p < 0.001; each comparison). When allergic asthmatic individuals were subdivided according to their age into two subgroups (Gr), no differences were found in eosinophil and lymphocyte counts and in PRIST levels and RAST values between Gr1 (< or =5 years old [preschool children]) and Gr2 (>5 years old [school children]) (p > 0.05; each comparison). Interestingly, although positive correlations between eosinophil counts and PRIST levels were found in both subgroups (p < 0.05; each comparison), only in Gr2 did eosinophil counts correlate positively with RAST classes (p < 0.001). No correlations between lymphocyte counts and PRIST levels or RAST classes were demonstrated (p > 0.05; each comparison). These data suggest that although blood eosinophilia was similar in preschool and in allergic asthmatic school children sensitized to HDM, only in the oldest children did blood eosinophil counts appear to be related to the degree of HDM-specific sensitization.     

Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly active in vitro against RSV A and B strains. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing. DESIGN: A Phase I/II multicenter, open label, escalating dose clinical trial. PATIENT POPULATION AND DOSING REGIMEN: Children (n=65) born prematurely at < or =35 weeks of gestation who were < or =6 months of age (n=41) and children with bronchopulmonary dysplasia who were < or =24 months of age (n=24) were enrolled. From 1 to 5 monthly injections were given at doses of 5 mg/kg (n=11), 10 mg/kg (n=6) and 15 mg/kg (n=48). Serum was collected before administration of each dose, 30 days after the last dose, and 2, 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay. RESULTS: The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies. Mean serum MEDI-493 concentrations were 91.1 microg/ml (range, 52.3 to 174.0) 2 days after the initial dose of 15 mg/kg and 49.2 microg/ml (range, 13.5 to 132.0) at 30 days. Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately 70 microg/ml. These concentrations were similar to previously published trough concentrations after i.v. administration. MEDI-493 injections were well-tolerated. Only three children had adverse events judged to be possibly related to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers (1:10 to 1:40) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg dose group were hospitalized for RSV; no RSV hospitalizations were found in the higher dose groups. CONCLUSIONS: MEDI-493 was safe and well-tolerated. Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 microg/ml (the value associated with 99% reduction of pulmonary RSV in the cotton rat model). These concentrations were similar to those previously reported with i.v. administration of MEDI-493.     

Distribution of total serum IgE and specific IgE to common aeroallergens by sex and age, and their relationship to each other in a random sample of the Dutch general population aged 20-70 years. Dutch ECRHS Group, European Community Respiratory Health Study

To describe the distribution of serum total IgE and specific IgE to common aeroallergens by sex and age and to study their relationship to each other, we measured serum total IgE and specific IgE (CAP) to house-dust mite, timothy grass, cat, birch, and Cladosporium in a random sample of 2496 subjects, aged 20-70 years from the Dutch general population. We found that total IgE was higher in men, independently of smoking, and that total IgE had no relationship with age after adjustment for specific IgE and smoking in linear regression analysis. At least one positive specific IgE test was found in 32% in both sexes. Men had higher prevalences of specific IgE to house-dust mite and lower prevalences of specific IgE to birch than women. The proportion with positive specific IgE decreased with age. The mean total IgE increased with the number of positive specific IgE tests. Thus, total IgE is higher in men and has no relationship with age if specific IgE is taken into account. The prevalences of specific IgE to aeroallergens are high and decrease with increasing age. We suggest that sex differences in total IgE should be considered when using total IgE.     

Comparison of cardiac findings at necropsy in octogenarians, nonagenarians, and centenarians

The Toxoplasma gondii rhoptry protein Rop2 was expressed in Escherichia coli as a fusion protein containing 44 kDa of the 55-kDa mature Rop2, supplied with six histidyl residues at the N-terminal end (Rop2196-561). Humoral response during Toxoplasma infection of humans was analyzed by immunoglobulin G (IgG), IgA, and IgM enzyme-linked immunosorbent assay with Rop2196-561 as the antigen substrate. The analyzed sera were divided according to T. gondii-specific serological tests (IgG, IgA, or IgM indirect immunofluorescence and IgA or IgM immunosorbent agglutination assay) as group A (IgG+ IgA- IgM-; n = 35), group B (IgG+ IgA+ IgM+; n = 21), group C (IgG+ IgA+ IgM-; n = 5), and group D (IgG+ IgA- IgM+; n = 16). Twenty-six T. gondii-seronegative sera from individuals with other infections were also included (group E). Anti-Rop2 IgG antibodies were detected in 82.8% of group A sera and in 97.6% of the sera with acute-phase marker immunoglobulins (groups B, C, and D). The percentage of IgA antibody reactivity against Rop2196-561 was 17.1% in group A, 50% in group D, and 80.8% in groups B and C. The percentage of IgM antibody reactivity was 0% in groups A and C and 62% in groups B and D. Sera from group E failed to show IgA, IgM, or IgG antibody reactivity. Since T. gondii Rop2 elicits a strong humoral response from an early stage of infection, it is suggested that recombinant Rop2196-561 would be suitable for use in diagnostic systems, in combination with other T. gondii antigens, to detect specific IgG, IgA, and IgM antibodies.