Development of allergies and asthma in infants and young children with atopic dermatitis--a prospective follow-up to 7 years of age.

BACKGROUND: The prognosis of atopic dermatitis is usually good, but the risk of developing asthma and allergic rhinitis is very high. The aim of this study was to follow children with atopic eczema up to school age to chart the course of sensitization and development of clinical allergy, as well as to study risk factors of sensitization. METHODS: Ninety-four children with atopic dermatitis were followed up to 7 years of age. The children were examined twice a year up to 3 years of age, and thereafter once yearly. At each visit, a clinical examination was performed, and a blood sample was taken. After 3 years of age, skin prick tests (SPTs) with inhalation allergens were performed at each visit. Information was obtained about atopy in the family, feeding patterns during infancy, symptoms of atopic disease, infections, and environmental factors. RESULTS: During the follow-up, the eczema improved in 82 of the 94 children, but 43% developed asthma and 45% allergic rhinitis. The risk of developing asthma was higher in children with a heredity of eczema. Presence of severe eczema at the time of inclusion in the study was associated with an increased tendency to produce food-specific IgE. An early onset of eczema was associated with an increased risk of sensitization to inhalant allergens, and development of urticaria. Early allergic reactions to food were associated with later reactions to food, allergic rhinitis, urticaria, and sensitization to both food and inhalant allergens. Early feeding patterns, time of weaning, and introduction of solid food did not influence the risk of development of allergic symptoms. A large number of periods or days with fever during the follow-up was associated with an increased risk of developing allergic rhinitis and urticaria. CONCLUSIONS: Our results confirm the good prognosis for the dermatitis and the increased risk of developing asthma and allergic rhinitis. Development of other allergic symptoms or sensitization was associated with the following factors: a family history of eczema, age at onset of eczema and its severity, early adverse reactions to foods, and proneness to infections.

Sensitization to airborne and food allergens in Reykjavík (Iceland) and Uppsala (Sweden) - a comparative study.

BACKGROUND: The aim of this study was to compare the prevalence of atopic sensitization and possible risk factors for allergies in two ethnically similar but geographically widely separated urban populations. METHODS: Data from two centers of the European Community Respiratory Health Survey, Reykjavik, Iceland, and Uppsala, Sweden, were utilized. This included a structured interview, skin prick tests, and blood samples for total and specific IgE for common aeroallergens. Additional measurements of specific IgE antibodies to common food antigens were performed. Furthermore, data on social environment, lifestyle, air pollution, and meteorologic variables were compared. RESULTS: Skin prick tests were done on 540 individuals in Reykjavik and 527 in Uppsala. The overall prevalence of at least one positive prick test was 20.5% in Reykjavik and 34.2% in Uppsala (P<0.001). Total and specific IgE were measured in serum from 521 subjects in Reykjavik and 472 in Uppsala. The geometric mean value for total IgE was significantly lower in Reykjavik (13.4 kU/l) than in Uppsala (24.7 kU/l) (P<0.001). Similarly, the overall prevalence of at least one specific IgE to airborne allergens was 23.6% in Reykjavik and 32.3% in Uppsala (P<0.01). Specific IgE to a food panel (fx5) was measured in 502 subjects in Reykjavik, and 434 in Uppsala. In Reykjavik, 20 individuals (4.0%) were positive to one or more of the allergens in the food panel compared to 27 (6.0%) in Uppsala. When the single allergens present in the food panel were measured, altogether 16 positive reactions were found in Reykjavik compared to 47 in Uppsala (P<0.05). CONCLUSIONS: The prevalence of sensitization to both airborne and food allergens was lower in Reykjavik than in Uppsala. The difference may be due to environmental and/or dietary differences or to some yet undefined factor.

Celiac disease in relation to immunologic serum markers, trace elements, and HLA-DR and DQ antigens in Swedish children with Down syndrome.

BACKGROUND: An association between Down syndrome and celiac disease has been reported. This study was conducted to determine the association between childhood celiac disease and Down syndrome in the county of Uppsala, Sweden. METHODS: All 76 children with Down syndrome (1-18 years) were screened for the occurrence of anti-gliadin antibodies (AGA) and anti-endomysium antibodies (EMA). Twelve children with suspected celiac disease were investigated further. RESULTS: Increased levels of both IgA and IgG AGA were found in 26% of the children and of EMA in and 5 of 76. Celiac disease was diagnosed in at least three of the children (3.9%; 95% confidence interval 0%-8.3%), and it could have been present in as many as eight. Three of the five EMA-positive children with suspected celiac disease had the HLA phenotype DR3, DQ2. CONCLUSIONS: The results show that determination of EMA is more useful as a screening test for celiac disease and for follow-up than is AGA in children with Down syndrome. The present study also confirms that celiac disease is overrepresented among Swedish children with Down syndrome and that celiac disease should be considered in all persons with Down syndrome.

Transitional statistics: internal migration and urban growth in post-Soviet Estonia.

PIP: Standard models and theories of internal migration and urban growth in Estonia have been developed. However, there remained a lack of statistical wherewithal to conduct the required kind of analysis. For instance, certain categories of migration are likely to have been underreported and it is clear that existing rules and regulations on how to report those moves that were registered were not always observed. This could be attributed to the fact that existing statistics may fail to account for the process they purposely capture. To illustrate, the authors report the results of a study of migration patterns in post-Soviet Estonia with a view of identifying the consequences of a change in reporting regulations and practices. To this end, a survey of individual migration histories was conducted in 1997. Overall, findings suggest that post-Soviet migration data are slightly improved in comparison with their Soviet-era predecessors: different but still deficient. It turns out that net domestic migratory flows are the reverse of what official statistics on registered residents suggest. The contrasts between the survey returns and the officially reported statistics are outlined, including resources of divergence. As the findings indicate that something is distinct from that suggested by the compilations of the Estonian Statistical Office is indeed taking place, this study provide some inputs for a more thorough understanding of how migratory flows and urbanization processes are transformed during the transition period itself.^ieng

On the move: explaining migration patterns in Estonia during the transition period.

PIP: This paper attempts to explore the migration patterns during the transition period in Estonia. A structuration approach was used to analyze data from the Estonian Statistical Office collected in 1997. Findings show that for migration between urban and rural areas, work-related reasons have been the most important motivating factor in urban growth during the transition period. Also considered are the family and education. In relation to sociodemographic structure of the population, men cite work, while women count family-related reasons, as the main motive for migrating. As to nonregistration, the most significant reason relates to issues of ownership. Because migrants are living in rented housing, it is not possible for them to register even if they desire to do so. Other reasons include "temporary", associated with study and work; "juridical", bureaucratic matters; and "multiple places of residence". This analysis, however, is incomplete because the attitudes and patterns of behavior have only partially or perfunctorily been related to the dramatic changes that have occurred in Estonian society. Proper statistical data are needed to help examine trends at a more disaggregated spatial level.^ieng

Production of antibodies to gliadin by peripheral blood lymphocytes in children with celiac disease: the use of an enzyme-linked immunospot technique for screening and follow-up.

Problems in the diagnosis of celiac disease are that a long time is needed between challenge with gluten and the appearance of the typical diagnostic morphologic signs in gut mucosa. Furthermore, local immunity to gliadin is only slowly and often incompletely mirrored by serum IgA anti-gliadin antibody (AGA) levels. It is known that a local IgA-associated immune response in the gut may be better and more quickly mirrored by an increase of circulating IgA-producing cells against the immunogen than by IgA serum antibodies. We have therefore used an enzyme-linked immunospot (ELISPOT) assay to enumerate IgA AGA spot-forming cells (SFC) in peripheral blood in 82 children with suspected celiac disease or with other gastrointestinal symptoms. The numbers of IgA AGA SFC/10(6) mononuclear cells were markedly increased in 17 patients with untreated (and later biopsy-verified) celiac disease compared with healthy children, children with nonceliac disease, and patients treated for celiac disease (p < 0.0001). In 20 children with celiac disease the numbers of IgA AGA SFC increased rapidly (p < 0.0001) after gluten challenge. As early as 2 wk after gluten challenge, 15/20 of these patients had abnormal levels of IgA AGA SFC, 6/20 patients had increased levels of serum IgA AGA, and 7/20 had IgA anti-endomysium antibodies. Our results indicate that analysis of IgA AGA production in peripheral blood cells may in further clinical studies provide a sensitive method for the diagnosis of celiac disease after a short time of gluten challenge.

Plasmapheresis in HLA-immunosensitized patients prior to kidney transplantation.

Immunosensitization against the human lymphocyte antigen (HLA) is a problem in most transplant centers. It prolongs the waiting list time in addition to risk of frequent acute rejections. To avoid these problems, various pretransplantation approaches have been attempted e.g. plasmapheresis (PP). The present retrospective study reports our experience with PP in this respect over a 5 year period. Twenty-three chronic hemodialysis patients with circulating panel reactive antibodies (> or = 50%) and previous kidney graft rejections were treated with 12 PP each. In addition to this, immunosuppression with cyclophosphamide and prednisolone were administered on the first day of PP and after tapering continued until transplantation. HLA-antibodies, as measured by the panel reactive antibodies and the antibody titer, decreased from about 70% to 30% (p < 0.001) and 5 steps of titerdilution, respectively with PP and immunosuppressive drugs; Twenty-two patients were transplanted with cadaveric grafts. Eight grafts were lost due to irreversible rejection, and one due to the patient's death 2 months after transplantation. The cumulative five-year graft survival at the time of follow-up was 59%. Adequate kidney function (serum creatinine mean 150 mumol/l) was observed in all grafts (n = 3) still functioning 60 months posttransplant. We conclude that pretransplantation plasmapheresis together with immunosuppressive drugs (cyclophosphamide and prednisolone) is useful in the removal of HLA antibodies in immunized patients awaiting kidney transplantation. It can be considered a valuable approach to increase the chances of successful transplantations.

Prevalence of sensitization to food allergens in adult Swedes.

BACKGROUND: The results from a population study on respiratory symptoms and bronchial hyperresponsiveness in relation to symptoms of food intolerance and sensitization to food allergens are reported. METHODS: The study included 1,812 men and women, aged 20 to 44 years and residents in three areas of Sweden who participated in the European Community Respiratory Health Survey. The prevalence of IgE sensitization to egg white, fish, wheat, peanut, soy, and milk was assayed by CAP-RAST and the prevalence of symptoms of food intolerance was determined by a standardized questionnaire. RESULTS: The study group included a random sample of 1,397 subjects from the general population at the three centers. Of these, 85 (6%) had specific IgE antibodies to one of the food allergens and 345 (25%) reported symptoms of food intolerance. After enrichment with subjects suffering from symptoms of asthma, the sample included a total of 1,812 individuals of which 144 subjects had specific IgE antibodies to one or more of the food allergens studied. Of these 144, 52% reported food intolerance but only 16% related the symptoms to any of the food allergens in the panel. Sensitization to food allergens was more common in atopic subjects, subjects reporting current asthma, and subjects with bronchial hyperresponsiveness (P < .001). These associations remained significant after adjustment for the degree of allergic sensitization, whether defined as the number of positive skin prick tests or as total serum IgE levels. CONCLUSIONS: Although sensitization to food allergens is not uncommon in adults, the correlation to specific symptoms of food intolerance is weak. Sensitization to food allergens may have special relevance to asthma and bronchial hyperresponsiveness.

Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin.

In a screening study concerning IgA and IgG antibodies to gliadin (IgA AGA and IgG AGA, respectively) in psoriasis, raised levels of IgA and AGA were found to be more common than in a reference group. To determine whether elevated AGA levels were associated with an increased number of intraepithelial lymphocytes, 33 patients with IgA AGA (n = 28) or IgG AGA (n = 5) values above 90% of the reference values (> 50 units/ml IgA AGA and < 12 units/ml IgG AGA) underwent gastroduodenoscopy and duodenal biopsy in a prospective study. For comparison, six patients with low levels of both IgA AGA and IgG AGA were included. Five biopsy specimens were taken in each patient. Paraffin-embedded specimens were examined with regard to the degree of intraepithelial lymphocyte infiltration, and scored from 0 to 3. Biopsy specimens with a score of 0 had one mononuclear cell or less per four epithelial cells. The specimens were also examined with regard to the presence of intraepithelial CD3+ T lymphocytes and gamma/delta+ T lymphocytes. In the six patients with low IgA AGA and low IgG AGA, the biopsy score was 0. Fourteen of the 33 patients with raised AGA had a score of > or = 1; of these, 12 had raised IgA AGA and two had slightly raised IgG AGA. Two of the patients with raised IgA AGA had partial villous atrophy, but the majority had normal villous architecture. There was a significant correlation both between the biopsy score and the number of intraepithelial CD3+ cells and between the score and the number of intraepithelial gamma/delta+ positive T lymphocytes. The serum IgA AGA levels were significantly correlated with the duodenal biopsy score, the number of intraepithelial gamma/delta+ T lymphocytes, and the number of CD3+ intraepithelial T lymphocytes. Most patients had no, or only mild, gastrointestinal symptoms. Of the 14 patients with biopsy scores > or = 1, seven had severe psoriasis and five moderately severe psoriasis, whereas only two had mild psoriasis. There was no relationship between the duodenal score and haemoglobin, folate, whole blood selenium or serum zinc levels. Some of these patients improve on a gluten-free diet, but it is still too early to draw any definite conclusions concerning the type of relationship between the skin lesions, the increased number of intraepithelial lymphocytes in the duodenal mucosa and gluten hypersensitivity.

Venom allergy in adult Swedes: a population study.

Hymenoptera allergies are a cause of considerable morbidity. However, deaths due to insect sting constitute a health hazard that can be minimized by effective therapy. We report the results of a study of 1815 men and women, aged 20-44 years and resident in three areas of Sweden. The prevalence of sensitization to the venom allergens of honeybees and wasps was assessed by RAST. Atopy and allergic diseases were considered possible risk factors for symptom development. Of the 1815 subjects, 1399 were randomly chosen from the general population. Of the random sample, 9.3% had specific bee or wasp IgE, 1.5% reported systemic reactions to bee or wasp stings, and 0.6% had both. Sensitization to bee or wasp correlated positively with atopy (odds ratio (OR) 2.0, confidence interval (CI) 1.4-2.8, P < 0.0001), male sex (OR 1.8, CI 1.3-2.5, P < 0.001), and age (OR 2.0, CI 1.4-2.8, P < 0.01), and negatively to living in the northernmost of the three centers (OR 0.4, CI 0.3-0.7, P < 0.001). Atopy was not found to be a risk factor for systemic reactions. We conclude that the prevalence of Hymenoptera allergy in Sweden is rather low when compared with other countries. Subjects with atopy seem to have an increased risk of becoming sensitized but do not develop systemic reactions more frequently than nonatopic subjects.

HLA antigen sharing in preeclampsia.

The association between human leukocyte antigens (HLA) and the development of preeclampsia (PE) was studied in 48 women with PE and their partners. In 20 of the families, the HLA antigens of the child were also determined. In 8 of 15 cases (53%) of primigravidae with PE, the child shared at least 2 paternal antigens with the mother, whereas this was the case in only 1 of 26 (4%) children of healthy mothers (p < 0.001). In contrast to this, none of 6 children of multigravidae with PE shared 2 paternal antigens with the mother. An increased homozygosity at the HLA-B locus was also seen in the children of primigravidae with PE (40 vs. 4%, p = 0.01).

Patients with psoriasis often have increased serum levels of IgA antibodies to gliadin.

It was recently observed that in six patients with psoriasis and one with palmoplantar pustulosis, with newly discovered gluten intolerance, a gluten-free diet had a remarkable effect on the skin lesions. This prompted us to undertake a screening investigation to discover whether increased levels of serum antibodies to gliadin are more common in patients with psoriasis than in healthy persons. IgA and IgG antibodies to gliadin (IgA AGA and IgG AGA) were quantified by a micro-ELISA method. Out of 302 patients with psoriasis, 16% (18 females, 31 males) showed serum IgA AGA levels above the 90th percentile value (51 u/ml) of the reference group. This tendency was even more marked when the proportion of patients with values > 70 u/ml was compared with the corresponding proportion of 99 reference subjects. Thus, 3% of the reference subjects but 7.9% of the patients had values > 70 u/ml. The corresponding figures for men were 1.6% and 8.9%, respectively. Men with psoriasis had a significantly higher mean IgA AGA than the male reference group. The means based on logarithmic values of the individual IgA AGA values were significantly higher in the psoriatic groups than in the reference groups. Although the mean level of IgG AGA was not increased in the psoriasis group, there was a correlation between the values for IgA AGA and IgG AGA. The serum concentrations of IgG, IgA and IgM were also measured. In the male patients, the mean IgA value was significantly increased. Women in whom IgA AGA was elevated also showed a significantly increased mean IgA.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunocompetent cells in human nasal polyps and normal mucosa.

The distribution of T- and B-lymphocytes, HLA-DR-expressing cells, and macrophages was determined using monoclonal antibodies in frozen biopsy sections of nasal polyps from 12 patients, and of nasal mucosa from five disease-free controls. The relative proportion and spatial distribution of different lymphoid cells was similar with regards to both nasal polyps and normal mucosa. Numerous scattered T lymphocytes (Leu4-positive) and HLA-DR-expressing macrophage/dendritic-like cells were shown and tended to accumulate in the subepithelial areas. Aggregates of T lymphocytes and HLA-DR-positive cells were also found close to deeper glands. In the submucosal clusters, the Leu3a-positive ("helper/inducer") cells were more common than the Leu2a-positive ("suppressor/cytotoxic") cells. Furthermore, a number of epithelial, non-lymphoid cells were found to express the HLA-DR antigen, which suggests an active role for the epithelium in the immunological response of the normal mucosa as well as that of the nasal polyp.

Pretransplantation immunoadsorption therapy in patients immunized with human lymphocyte antigen: effect of treatment and three years' clinical follow-up of grafts.

Sensitization against human lymphocyte antigen (HLA) occurs frequently in previously transplanted patients that lose a first cadaveric graft. To shorten their time on the waiting list and reduce the incidence of early rejection in such patients, we performed immunoadsorption therapy by a tryptophan column in 10 patients as an attempt to remove circulating antibodies prior to regrafting. Resynthesis of antibodies was suppressed with cyclophosphamide and prednisolone. Following the course of immunoadsorption therapy, the panel reactive antibodies (PRA) decreased by more than 50% from the pretreatment values. In the present study, 8 patients were transplanted with cadaveric renal grafts. At the time of follow-up, graft survival was 63% in these patients (2-36 months post-transplantation, mean 23 months). There was one incidence of acute rejection, one graft was lost within 48 h owing to renal artery thrombosis, and one was lost within 2 weeks as a result of stenosis. The serum creatinine levels were down to near normal during the first 3 weeks in hospital (p < 0.0001) and remained at this level during the period of follow-up. We conclude that immunoadsorption might be a beneficial pretransplantation therapy and an alternative to plasmapheresis in HLA-immunized patients awaiting kidney transplantation.

Urbanisation, central planning and Tolley's model of urban growth: a critical review.

The authors assess a model of urban growth developed by G. S. Tolley, with a focus on "the model's potential contribution towards an improved comprehension of urbanisation in socialist polities. Although previous studies indicate that Tolley's model would seem to fit developments in China and that of other Soviet-type economies in a rather congenial manner, it is here suggested that it is not fully appropriate."

Jejunal secretion of secretory immunoglobulins and gliadin antibodies in celiac disease.

The aim of this study was to determine the secretion of secretory immunoglobulins and gliadin antibodies in the small bowel in celiac disease. Twenty-four patients were investigated by perfusion of a defined jejunal segment. Four of the patients studied had a serum IgA deficiency and had no measurable amounts of secretory IgA in the perfusion fluid. The other patients demonstrated a significant increase in the jejunal concentration of secretory IgA (median 28.5 mg/liter) compared with healthy controls (median 16 mg/liter, N = 16) and of IgM, celiac (median 12.3 mg/liter) compared to healthy controls (median 6.8 mg/liter, N = 16). Jejunal IgA gliadin antibodies were detected in all patients except those with an IgA deficiency. All patients had jejunal IgM gliadin antibodies, but none of the patients had measurable jejunal IgG gliadin antibodies. A positive correlation was detected between serum and jejunal IgA gliadin antibody levels in the celiac patients, (P less than 0.01). Calculation of the ratio between gliadin antibodies and total levels of IgA and IgM in serum and jejunal perfusate demonstrated that the jejunal synthesis of gliadin antibodies of IgA and IgM type is both more pronounced and persistent than the systemic humoral immune response to gliadin.

Is repeated mismatching at regrafting deleterious?

We reviewed our clinical experience of allowing kidney regrafting with a repeated HLA mismatch. We also permitted a weakly positive B-cell cross-match. All patients who received a second or subsequent renal graft (n = 92) between January 1985 and June 1990 were analysed for graft survival. The overall 1-year graft survival was 70%. A repeated mismatch occurred in 29 of the patients at at least one HLA locus and their 1-year graft survival was 66%. The balance of the regrafts (63) were performed without a repeated mismatch, and their 1-year graft survival was 70%. Even a weakly positive B-cell cross-match was deleterious; when a grafting with a repeated mismatch was performed only one out of five grafts survived. Our results indicate that retransplantation of renal grafts with a repeated mismatch in the HLA A or B locus can be performed without a negative influence on transplant outcome provided that both the T- and B-cell cross-matches are negative.

Underurbanisation and the zero urban growth hypothesis: diverted migration in Albania.

The author challenges the hypothesis "that the mode of production accounts for the specific forms of urbanisation under socialism and the slow urban growth observed...[and emphasizes instead] the effects of planning in the traditionally organised command economy." It is suggested that strict migration policy is a pivotal factor in achieving zero urban growth. "A case study focusing on patterns of diverted migration and the growth of non-urban settlements on the outskirts of the Albanian capital, Tirana, illustrates how the proposed explanations may help to re-interpret the particulars of urbanisation under orthodox socialist rule."

Enumeration of IgA producing cells by the enzyme linked immunospot (ELISPOT) technique to evaluate sulphasalazine effects in inflammatory arthritides.

Numbers of IgA producing cells in peripheral blood were determined by the enzyme linked immunospot (ELISPOT) technique in 15 patients with inflammatory arthritides receiving sulphasalazine treatment. The numbers of IgA producing cells decreased significantly after the first three weeks of treatment. In 11 of the patients this decrease persisted, whereas a subsequent increase was seen in the four others; in two of these latter patients this increase coincided with a temporary withdrawal of the sulphasalazine treatment. A reduction of serum concentrations of IgA and haptoglobin was seen after three months' treatment. Eleven of the patients had a subjective improvement in their joint disease during the first three months of treatment. Analysis of circulating cells committed for IgA secretion may constitute one way of assessing gut associated immunity indirectly, and the present data suggest that sulphasalazine has a rapid effect on lymphocytes possibly originating from the gut and that such an effect precedes improvement in laboratory parameters and clinical symptoms in arthritic diseases.