Early allergic sensitizations and their relevance to atopic diseases in children aged 6 years: results of the GINI study.

BACKGROUND: Only a few studies have analyzed the value of early sensitization in predicting the development of atopic disease. The relevance of low immunoglobulin (Ig) E antibody levels in this respect also remains unclear. OBJECTIVE: To investigate the relevance of sensitization in 12-month-old children in the development of atopic disease by the age of 6 years. METHODS: We analyzed data for 1290 children with a positive family history of atopy from the prospective, multicenter German Infant Nutritional Intervention (GINIplus) study and investigated the relationship between the presence of detectable specific IgE antibodies at the age of 12 months and the development of atopic disease by the age of 6 years. RESULTS: In all, 10.9% of children analyzed developed sensitization. At the age of 6 years, 20.6% of children with early sensitization had eczema compared to 9.4% of those without (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.42-3.74). The corresponding figures were 15.4% vs 7.3% for allergic rhinitis (OR, 2.22; CI, 1.31-3.78) and 10.2% vs 2.6% (OR, 3.93; 95% CI, 1.98-7.76) for asthma. Children with early sensitization to aeroallergens had the greatest risk of subsequent atopic disease. Early sensitization did not increase risk in children without eczema within the first year of life. Very low specific IgE levels (0.18-0.34 kU/L) were not significantly associated with any of the outcomes analyzed. CONCLUSION: Sensitization to common food allergens and to aeroallergens in particular during the first year of life was found to be a strong predictor for the development of atopic disease by the age of 6 years in children with a positive family history of atopy.

Expression of mRNA for cytokines (TNF-alpha and IL-1alpha) in human cytomegalovirus (HCMV) and hepatitis B virus (HBV) infections.

The study was aimed at detecting cellular sources of transcripts for two cytokines, TNF-alpha and IL-1alpha in infection with human cytomegalovirus (HCMV) or hepatitis B virus (HBV). The studies were performed on paraffin sections of organs (liver, pancreas, spleen, lungs) obtained upon autopsy from a child deceased due to acute inborn HCMV infection, on paraffin sections of liver biopsy, obtained from a child with HCMV-induced chronic hepatitis, and of liver biopsies obtained from children with chronic type B hepatitis (n = 13). The classical in situ hybridization was applied with digoxygenin-labeled probes and amplification by the ImmunoMax technique. In HCMV infection, the most pronounced expression of mRNA for TNF-alpha and Il-1alpha was detected in pancreatic islets (mainly in beta cells) and, then, in a decreasing sequence, in liver (in macrophages and sinusoidal endothelial cells) and in lungs (in alveolar macrophages). No expression of the two cytokines was detected in the spleen. In HBV infection, weak expression of TNF-alpha and more intense expression of IL-1alpha in the liver were observed, mainly in sinusoidal endothelial cells and in macrophages as well as in hepatocytes. These results were confirmed by immunocytochemical experiments.

Epidemiology of food allergy/food intolerance in adults: associations with other manifestations of atopy.

BACKGROUND: Food allergy and food intolerance (FA/FI) are believed to be frequent medical problems; however, information from epidemiologic studies in adults is scarce. The objective was to determine the frequency of FA/FI and allergic sensitization to food in a large adult sample. Furthermore, the associations between FA/FI and other outcomes of atopy were studied. METHODS: Within a population-based, nested, case-control study, a standardized interview was performed to obtain detailed information on FA/FI and the history of atopic diseases. In addition, a skin prick test with 10 common food and nine aeroallergens was performed. RESULTS: Overall, 20.8% of the 1537 studied subjects (50.4% female, age median 50 years) reported FA/FI (women 27.5%, men 14.0%; OR 2.35, CI 1.80-3.08). Nuts, fruits, and milk most frequently led to adverse effects, and the sites of manifestation were oral (42.9%), skin (28.7%), gastrointestinal (13.0%), systemic (3.2%), and multiple (12.2%). One-quarter of the subjects (25.1%) were sensitized to at least one food allergen in the prick test, with hazelnut (17.8%), celery (14.6%), and peanut (11.1%) accounting for most of the positive reactions. The corresponding frequency estimates for the representative study base (n=4178) were 15.5% for reported adverse reactions and 16.8% for allergic sensitization. Relevant concomitant sensitization to food and aeroallergens was observed. Food-allergic subjects (positive history and sensitization to corresponding allergen) suffered significantly more often from urticaria, asthma, atopic eczema, and especially hay fever (73.1%) than controls (3.0%). Furthermore, hay fever was treated significantly more often in subjects who suffered from concomitant food allergy. CONCLUSIONS: FA/FI in adults is frequently reported and associated with other manifestations of atopy. Hay fever in conjunction with FA/FI tends to be clinically more severe since therapeutic needs are enhanced.

Epidemiology of contact allergy in adults.

BACKGROUND: We aimed to determine the prevalence of contact sensitization in the general population and to investigate associations with important sociodemographic and medical characteristics. METHODS: Within a population-based nested, case-control study in Germany, we performed patch tests with 25 standard allergens in 1141 adults (50.4% female, age median 50 years). Additional information was obtained by a dermatologic examination, a standardized interview, and blood analysis. RESULTS: At least one positive reaction was exhibited by 40.0% of the subjects, with reactions most frequently observed to fragrance mix (15.9%), nickel (13.1%), thimerosal (4.7%), and balsam of Peru (3.8%). Women were sensitized more often than men (50.2% vs 29.9%, OR 2.36, CI 1.84-3.03), and this was also significant for fragrance mix, nickel, turpentine, cobalt chloride, and thimerosal. Contact sensitization was more frequent in subjects who reported adverse skin reactions (53.8% vs. 32.6%; OR 2.41, CI 1.85-3.14), and this was particularly true for sensitization to nickel (45.5% vs 8.8%, OR 8.64, CI 5.67-13.17) and fragrance mix (29.0% vs 14.0%, OR 2.51, CI 1.60-3.91) and the corresponding intolerance of fashion jewelry and fragrances. Contact sensitization decreased with increasing degree of occupational training (unskilled 45.9%, apprenticeship 40.1%, technical college 40.4%, and school of engineering 12.5%; P=0.023; trend test P=0.042). Significant associations of contact sensitization and presence of allergen-specific IgE antibodies, atopic eczema, or psoriasis were not observed. Frequency estimates for the general adult population based on these findings were 28.0% for overall contact sensitization and 11.4% for fragrance mix, 9.9% for nickel, and 3.2% for thimerosal. CONCLUSIONS: It is concluded that contact allergy is influenced by sociodemographic parameters and plays an important role in the general population.

Farming, rural lifestyle and atopy in adults from southern Germany--results from the MONICA/KORA study Augsburg.

BACKGROUND AND OBJECTIVE: The increasing urbanization and the decrease in the numbers of farms in southern Germany might be associated with an increasing prevalence of allergic diseases. We compared the prevalence of allergic diseases in farmers, and rural, suburban and urban residents in the small geographical area of Augsburg in southern Germany. METHODS: In a cross-sectional survey adults, aged 25-75 years selected from the community population register were investigated. Rural, suburban and urban residents were defined by community size and farmers by occupation. Allergic respiratory disorders were assessed by self-administered questionnaires and specific IgE antibodies to five common aeroallergens. RESULTS: In comparison to rural residents the urban population had an increased risk of allergic rhinitis (OR = 1.5; 95% CI: 1.2-1.9), atopic sensitization (OR = 1.2; 95% CI: 1.0-1.4) and sensitization against pollen (OR = 1.5; 95% CI: 1.2-1.9). There was no difference in the risk of asthma (OR = 1.0; 95% CI: 0.6-1.6) and a decreased risk in the sensitization against house dust mite (OR = 0.8; 95% CI: 0.7-1.0). The suburban residents did not differ from urban residents. Farmers had lower risks in allergic rhinitis, atopic sensitization, sensitization against pollen and mites (OR = 0.63; 0.86; 0.51 and 0.80, respectively) than rural non-farming residents, however, these differences were statistically not significant. Reported allergic rhinitis with sensitization to pollen was 2.5 times (95% CI: 1.8-3.6) more prevalent in urban than in rural residents. CONCLUSION: A farming environment and rural lifestyle might be associated with unknown protective factors impacting the prevalence of allergies.

The distribution in specific IgE and the prevalence of allergic symptoms in 25-64-years old inhabitants of an eastern and a western German city--results from Augsburg and Erfurt.

BACKGROUND: In an earlier study it has been found that allergic symptoms and sensitization in adults were more frequent in Hamburg (northern part of West Germany) compared to Erfurt (East Germany). The purpose of this study was to replicate these findings using data from Augsburg, a city from the southern part of West Germany. Furthermore the study population in this analysis was extended to higher age groups. METHODS: The prevalence of respiratory symptoms, assessed by a self-administered questionnaire, was compared in a random sample of adults, 25-64 years of age, living in Augsburg (n = 1572) and Erfurt (n = 1648). From a subset (n = 754, resp. 1144) specific IgE to common aeroallergens were measured and atopic sensitization was defined as the presence of at least one positive specific IgE (CAP > 0). RESULTS: The prevalence of allergic rhinitis, wheezing, asthma and atopic sensitization was higher in Augsburg than in Erfurt (OR: 2.0; 1.3; 2.1; 1.7; all p < 0.01). For these differences no specific explanation could be found, i.e. the percentage of sensitized persons was equally increased in Augsburg for asthmatics, patients with hay fever or asymptomatic subjects. Furthermore, sensitization was equally increased for all common allergens. The differences were largest for the youngest age group, but also existed for higher ages. CONCLUSIONS: The increased prevalence of allergies observed in Hamburg, a northern city of West Germany, is also found in Augsburg, a southern city of West Germany, both compared to Erfurt in East Germany. This supports the finding that unspecific causes related to western lifestyle play an important role. Further research is needed to identify the causal influences.

Cellular expression of TNF-alpha in human cytomegalovirus (HCMV) infection.

Human cytomegalovirus (HCMV) belongs to the most frequent human pathogens. Even if the respective pathomorphological patterns are known in detail, the mechanisms which lead to persistence of the virus in its latent form, its reactivation as well as mechanisms of cell death in the symptomatic infection remain to be clarified. It is postulated that HCMV controls expression of TNF-alpha gene and the associated secondary inflammatory response. On the other hand, TNF-alpha has been shown in in vitro studies to represent a potential stimulator of HCMV major IE promoter. The present studies have been aimed at evaluation of TNF-alpha expression in HCMV-infected brain, liver, kidney and pancreas, obtained upon autopsy from children deceased due to an inborn HCMV infection. In situ hybridisation using digoxigenin-labelled oligonucleotide probe demonstrated the expression of TNF-alpha transcript in the liver (in macrophages and endothelial cells) and in pancreatic islets of Langerhans (in beta cells). Immunocytochemical studies aimed at detection of TNF-alpha protein in the material yielded negative results.

Long-term effect of neonatal monosodium glutamate (MSG) treatment on reproductive system of the female rat.

The study aimed at determining effects of monosodium glutamate (MSG), introduced in the perinatal period, on the reproductive system of sexually mature female rats. In days 2, 4, 6, 8, 10 the newborns received s.c. injections of MSG (4 mg/g body weight) or 2% NaCl solution. When the animals reached the age of 6, 12 or 18 months, their ovaries and uteri were isolated for histological and morphometric studies while in their sera estradiol level was estimated by the RIA technique. The perinatal injection of MSG was found to decrease relative weights of ovaries and uteri. In the ovaries increased numbers of primordial follicles and decreased numbers of graafian follicles were detected. Also the thickness of endometrium and of the epithelium, which lined the endometrium, were lowered in females, which received perinatal injections of MSG, as compared to the controls. Serum estradiol level in MSG injected females was lowered at the age of 12 and 18 months. In 12 and 18 month old females the alterations were accompanied by obesity and a decreased body length.

[External quality control in the Federal Health Survey: concept and site visits]. / Externe Qualitätskontrolle im Bundes-Gesundheitssurvey: Konzept und Site-Visits.

The results of the German National Health Interview and Examination Survey will be of great importance for health policy and research. Therefore, internal quality management was supplemented by an external quality control which was carried out by a private company (Bernhard Schwertner Feld organisation, Augsburg). The interviewer training, sampling and response, field work and data management were included into the external quality control. For each of these four areas, measures of control and detailed check-lists were provided by the external quality control. The aim was to find sources of potential and real errors and to arrive at recommendations for internal quality management. The general concept of external quality control is briefly presented and experiences and results from the quality control of the field work are described in the present paper.

Classical risk factors and their impact on incident non-fatal and fatal myocardial infarction and all-cause mortality in southern Germany. Results from the MONICA Augsburg cohort study 1984-1992. Monitoring Trends and Determinants in Cardiovascular Diseases.

BACKGROUND: The MONICA (Monitoring Trends and Determinants in Cardiovascular Diseases) project in Augsburg provides the first population-based cohort study in Germany to quantify the associations of the risk factors hypertension, hypercholesterolaemia and smoking with incident non-fatal and fatal myocardial infarction and all-cause mortality, and to assess their impact at the population level. METHODS: The cohort comprises 1074 men and 1013 women aged 45-64 years; they were followed over 8 years from 1984-1992. In the men, there were 61 non-fatal and fatal myocardial infarctions and 92 all-cause mortality events over this period; in the women the number of deaths from all causes was 45. Incidence rates, hazard rate ratios, population attributable fractions and rate advancement periods were calculated. RESULTS: Adjusting for confounders, the myocardial infarction hazard rate ratios for men with hypertension, or a total cholesterol/HDL-cholesterol ratio > or =5.5, or smoking > or =20 cigarettes/day, were 2.0 (95% CI 1.2-3.5), 2.9 (95%, CI 1.7-5.0), and 2.7 (95% confidence interval (CI) 1 4-5.0), respectively. The risk factor combination total cholesterol/HDL cholesterol ratio > or = 5.5 and cigarette smoking was particularly hazardous. The three risk factors contributed 65% of the burden of myocardial infarction in the population. The rate advancement period for myocardial infarction associated with hypertension, total cholesterol/HDL cholesterol ratio > or =5.5 or smoking > or =20 cigarettes/day was 8.3, 12.4 and 11.5 years, respectively. In women, these risk factors were similarly predictive of all-cause mortality. Comparing the cohort data from Augsburg with those of two occupational cohorts from Germany reveals higher absolute myocardial infarction risks in the Augsburg population; however, the relative risk estimates in the Augsburg and the two occupational cohorts were very similar. CONCLUSION: Our results confirm the important contribution of the classical risk factors to the risk of myocardial infarction and all-cause mortality in Germany. The results pertaining to the concept of rate advancement periods particularly demonstrate the great potential for prevention.

[Family status and social integration as predictors of mortality: a 5-year follow-up study of 55- to 74-year-old men and women in the Augsburg area]. / Familienstand und soziale Integration als Prädiktoren der Mortalität: eine 5-Jahres-Follow-up-Studie an 55- bis 74jährigen Männern und Frauen in der Region Augsburg.

The relation between marital status, social integration and the mortality from all causes was examined in a population based cohort study. The 5-year-cohort consisted of 1,030 men and 957 women, aged 55-74 years who participated in the second MONICA Survey Augsburg, F.R.G., 1989/90 (MONICA = Monitoring of trends and determinants of cardiovascular disease). They were followed for mortality until 1995. Altogether 120 men and 45 women had died. Social integration was measured by an index of social ties. The index of social ties examined in these analyses includes (a) presence of a spouse, (b) number of close friends and relatives, (c) reported contact with close friends and relatives. Age standardized mortality rates (per 10,000 person years) were computed for men and women. Sex-specific Cox-proportional hazard models were used and hazard rate ratios (HRR) were calculated adjusting for age, hypertension, cigarette smoking, cholesterol, drinking alcohol, number of chronic diseases and self-reported health. Mortality rates were higher for men who were living alone (437.3) than for married men (235.3). Respectively in women the rates were 121.6 compared to 80.7. After controlling for age and self-reported health a HRR of 1.5 (95% CI: 1.0-2.4) was observed for single, divorced or widowed men and a HRR of 1.6 (95% CI: 0.8-3.0) for women living alone. Low mortality rates were observed in people with many social ties (men: 180.1, women: 29.9). Mortality rates of people who gave no informations about social ties (men: 349.5, women: 124.9) were similar to those who had only few social ties (men: 321.1, women: 132.5). The findings showed that people with few social ties were more likely to die in the follow-up period than those with more extensive contacts. After adjusting for age and self-reported health the HRR for those with few ties compared to those with many social ties were 1.6 (95% CI: 1.1-2.5) for men and 2.7 (95% CI: 1.1-6.6) for women. Similar results were found for people who gave no informations about their social ties (men: HRR = 1.4, 95% CI: 0.9-2.3; women: HRR = 2.6, 95% CI: 1.0-6.9). Social relationships were shown to be important predictors of mortality in elderly women and men. These findings confirm the need for further research, which enables to take steps against high mortality of the social isolated elderly.

Plasma viscosity and the risk of coronary heart disease: results from the MONICA-Augsburg Cohort Study, 1984 to 1992.

Plasma viscosity is determined by various macromolecules, eg, fibrinogen, immunoglobulins, and lipoproteins. It may therefore reflect several aspects involved in cardiovascular diseases, including the effects of classic risk factors, hemostatic disturbances, and inflammation. We examined the association of plasma viscosity with the incidence of a first major coronary heart disease event (CHD; fatal and nonfatal myocardial infarction and cardiac death; n=50) in 933 men aged 45 to 64 years of the MONICA project of Augsburg, Germany. The incidence rate was 7.23 per 1000 person-years (95% confidence interval [CI], 5.37 to 9.53), and the subjects were followed up for 8 years. All suspected cases of an incident CHD event were classified according to the MONICA protocol. There was a positive and statistically significant unadjusted relationship between plasma viscosity and the incidence of CHD. The relative risk of CHD events associated with a 1-SD increase in plasma viscosity (0.070 mPa x s) was 1.60 (95% CI, 1.25 to 2.03). After adjustment for age, total cholesterol, high density lipoprotein cholesterol, smoking, blood pressure, and body mass index, the relative risk was reduced only moderately (1.42; 95% CI, 1.09 to 1.86). The relative risk of CHD events for men in the highest quintile of the plasma viscosity distribution in comparison with the lowest quintile was 3.31 (95% CI, 1.19 to 9.25) after adjustment for the aforementioned variables. A large proportion of events (40%) occurred among men in the highest quintile. These findings suggest that plasma viscosity may have considerable potential to identify subjects at risk for CHD events.

Alcohol, blood pressure and hypertension.

In the last 30 years a large number of cross-sectional studies, a smaller number of prospective cohort studies and several intervention studies have addressed the alcohol-blood pressure relationship. Although a number of questions--such as the validity of measurement of alcohol intake, shape of the alcohol-blood pressure relationship, threshold dose for hypertension, and plausible pathophysiological mechanisms--have not yet been answered satisfactorily, it is clear that a causal association exists between chronic intake of > or = 30-60 g alcohol per day and blood pressure elevation in men and women. To call the alcohol-blood pressure relationship causal is justified because chance and, to a large degree, bias and confounding, have been ruled out as plausible explanations in most observational studies. More importantly, the intervention studies support the observational studies and show a remarkable consistency in demonstrating a potentially valuable decrease in blood pressure when heavy drinkers abstain or restrict their alcohol intake. From the different studies a rule of thumb can be derived: above 30 g of alcohol intake per day an increment of 10 g of alcohol per day increases on average systolic blood pressure by 1-2 mmHg and diastolic blood pressure by 1 mmHg.

Trends in coronary heart disease morbidity and mortality and acute coronary care and case fatality from 1985-1989 in southern Germany and south-western France.

BACKGROUND: Although it has been shown that coronary heart disease mortality rates are decreasing in industrialized countries, little is known about time trends in coronary heart disease incidence. Further, although a number of randomized clinical trials have shown that percutaneous transluminal coronary angioplasty and thrombolysis improve survival of acute myocardial infarction patients, it is not known if widespread use of these therapeutic procedures has contributed to a decrease in in-hospital case fatality on a population basis. METHODS: The change over time of coronary heart disease attack, incidence and mortality rates was assessed in men and women (35 to 64 years) using data collected between 1985 and 1989 by the Augsburg (Germany) and Toulouse (France) MONICA Centres. Acute coronary care and 28-day case fatality for hospitalized 24-h survivors were also assessed. RESULTS: Men and women from Augsburg had higher age-standarized attack, incidence and mortality rates than their Toulouse counterparts. In both centres, attack, incidence and mortality rates declined in men, but increased in women. Patients in Toulouse received more percutaneous transluminal coronary angioplasty and thrombolysis and had lower 28-day case fatality than patients in Augsburg. The therapeutic procedures, percutaneous transluminal coronary angioplasty and thrombolysis increased in both centres; however, only in Toulouse was this increase associated with a decrease (non significant) in 28-day hospital case fatality. CONCLUSION: The increase in morbidity and mortality rates of coronary heart disease in women stresses the need for preventive measures in this group. The absence of a favourable effect of acute coronary care on 28-day fatality for hospitalized 24-h survivors in the Augsburg centre will be further investigated.

The relation of alcohol intake to coronary heart disease and all-cause mortality in a beer-drinking population.

Epidemiologic studies indicate that light to moderate alcohol consumption from beer, wine, or spirits is associated with a reduction in all-cause mortality, owing primarily to a reduced risk of coronary heart disease (CHD). To find out whether this protective effect of small to moderate amounts of alcohol could be confirmed in Germany, where much of the alcohol consumed is taken in the form of beer, we studied the relation between alcohol and CHD and total mortality in a population of southern Germany. We conducted a prospective cohort study from 1984 to 1992 among 1,071 men and 1,013 women, age 45-64 years at baseline, from the Augsburg region. Eighty-seven per cent of men and 56% of women reported drinking alcohol at baseline. Among drinkers, men had an average alcohol intake of 42 gm per day, of which 33 gm per day came from beer. Women who drank had an average alcohol intake of 16 gm per day and derived about half of it from beer and the other half from wine. During the 8 years of follow-up, 96 deaths (all causes) and 62 incident CHD events (nonfatal and fatal) occurred in men, and 45 deaths (all causes) occurred in women. Adjusting for a number of potential confounders, in men the adjusted hazard rate ratio (HRR) of CHD events for drinkers as compared with nondrinkers was 0.51 [95% confidence interval (CI) = 0.27-0.95]; this protective effect starts with the 0.1-19.9 gm per day alcohol category and does not change much with higher intake. In men, the adjusted total mortality HRR for drinkers as compared with nondrinkers was 0.59 (95% CI = 0.36-0.97). The total mortality HRRs for the different alcohol groups compared with nondrinkers show a U-shaped curve, with the lowest HRR of 0.46 (95% CI = 0.20-0.80) for the 20-39.9 gm per day alcohol group and an HRR of 1.04 (95% CI = 0.54-2.00) for the > or = 80 gm per day alcohol group. In women, the total mortality HRR for those drinking up to 19.9 gm per day as compared with nondrinkers was 0.46 (95% CI = 0.22-0.96).

Relations of changes in coronary disease rates and changes in risk factor levels: methodological issues and a practical example.

One of the main hypotheses of the World Health Organization (WHO) MONICA Project is that trends in the major coronary disease risk factors are related to trends in rates of fatal and non-fatal coronary disease events. The units of study are populations rather than individuals. The WHO MONICA Project involves continuous monitoring of all coronary disease events in the populations over a 10-year period and periodic risk factor surveys in random samples of the same populations. Estimation of associations between average annual changes in mortality and risk factor levels is illustrated with the use of data from a subset of MONICA centers. Crude estimates of regression coefficients are compared with estimates obtained by weighting for standard errors in both the outcome and explanatory variables. The results show that the strength of association may be either underestimated or overestimated if these errors are not taken into account.