Pregnancy and perinatal conditions and atopic disease prevalence in childhood and adulthood.

BACKGROUND: Previous studies showed controversial results for the influence of pregnancy-related and perinatal factors on subsequent respiratory and atopic diseases in children. The aim of this study was to assess the association between perinatal variables and the prevalence of asthma, bronchial hyperreactivity (BHR), flexural eczema (FE), allergic rhinitis, and sensitization in childhood and early adulthood. METHODS: The studied population was first examined in Munich and Dresden in 1995/1996 at age 9-11 years. Participants were followed until age 19-24 years using questionnaires and clinical examinations. Associations between perinatal data and subsequent atopic diseases were examined using logistic regression analyses adjusting for potential confounders. RESULTS: Cesarean section was statistically significantly associated with BHR in early adulthood (odds ratio 4.8 [95% confidence interval 1.5-15.2]), while assisted birth was associated with presence of asthma symptoms in childhood (2.2 [1.2-3.9]), FE symptoms (2.2 [1.2-4.3]) and doctor's diagnosis of atopic dermatitis (1.9 [1.0-3.4]) in childhood, and sensitization in early adulthood (2.2 [1.1-4.3]). Lower birth length (1.9 [1.1-3.2]), lower birthweight (0.5 [0.3-0.9]), and higher birthweight (0.6 [0.4-1.0]) were predictive of sensitization in early adulthood compared to average birth length and birthweight, respectively. None of the other perinatal factors showed statistically significant associations with the outcomes. CONCLUSIONS: Our results indicate that children who are born by cesarean section and especially by assisted birth, might be at greater risk for developing asthma, FE, and sensitization and should hence be monitored. Prenatal maternal stress might partly explain these associations, which should be further investigated.

[Children and Adolescents in Need of Long-Term Care. An Analysis of Data Obtained by the Medical Service of Compulsory Health Insurance Funds, MDK Bavaria]. / Pflegebedürftigkeit nach SGB XI bei Kindern und Jugendlichen. Eine Analyse der Pflegebegutachtung des MDK Bayern.

Children and adolescents among those in need of long-term care differ significantly from older long-term care patients. The aim of this investigation was to characterise the features of this group. We analysed 6,141 records of children and adolescents produced in 2011 by the medical service of the statutory health insurance of Bavaria. The need for long-term care usually occurred before school age, initially mainly to care level 1. Typically, support for long-term care was initially applied for with the diagnosis of severe developmental disorder. Most likely, a care level was recommended for children with malignant diseases. The majority of children requiring long-term care suffered from Down syndrome, developmental disorders and cerebral palsy. In the population group, 60% were male. Typically, most of the assistance was needed for personal hygiene, however the higher the care level required the more time was needed for nourishment. Only few children regained age-appropriate independence. The majority of the children requiring long-term care for congenital diseases or those present at a young age stay dependent on outside assistance permanently.

Management of occupational asthma: cessation or reduction of exposure? A systematic review of available evidence.

Reduction of exposure to sensitising agents causing occupational asthma has been proposed as an alternative to total avoidance in order to minimise the adverse socio-economic impact of the condition. The aim of this systematic review was to compare the effects of these two management options on asthma and socio-economic outcomes. A bibliographic search was conducted to identify studies examining the outcome of workers with occupational asthma after reduction or cessation of exposure to the causal agent. The changes in asthma symptoms and nonspecific bronchial hyperresponsiveness after reduction or cessation of exposure were described in nine and five studies, respectively. The meta-analysis of pooled data showed that a reduction of exposure was associated with a lower likelihood of improvement (OR 0.16, 95% CI 0.03-0.91) and recovery (OR 0.30, 95% CI 0.11-0.84) of asthma symptoms and a higher risk of worsening of the symptoms (OR 10.23, 95% CI 2.97-35.28) and nonspecific bronchial hyperresponsiveness (OR 5.65, 95% CI 1.11-28.82), compared with complete avoidance of exposure. This systematic review indicates that reduction of exposure cannot be routinely recommended as an alternative to cessation of exposure in the management of occupational asthma. However, further investigations are required before drawing evidence-based conclusions on the cost-effectiveness of this approach.

Educational intervention in farmers with occupational asthma: long-term effect on exhaled nitric oxide.

BACKGROUND: The fraction of exhaled nitric oxide (FE(NO)) has been found reduced 4 to 6 weeks after an educational intervention in farmers with occupational asthma. OBJECTIVE: To reveal whether long-term changes in FE(NO) would still be detectable a year after the intervention. METHODS: We evaluated airway inflammation and obstruction at baseline and after 1 year in animal farmers with occupational asthma (n = 43, 16 women, mean [SD] age, 46.5 [8.9] years) who participated in a 1-day educational program, and in a control group of farmers without intervention (n = 15, 3 women, mean age, 44.1 [10.7] years). FE(NO), spirometry results, and questionnaire data were compared between measurements and between the intervention and control group. RESULTS: In the intervention group, geometric mean (SEM) FE(NO) decreased from 31.5 (1.1) to 25.0 (1.1) parts per billion (ppb) (P = .001), whereas in the control group there was a slight but not statistically significant increase from 27.2 (1.2) to 30.7 (1.2) ppb. Spirometric values remained unchanged in both groups. CONCLUSIONS: We found that FE(NO) was still decreased 1 year after an educational intervention in farmers with occupational asthma. It would thus seem that FE(NO), a noninvasive marker of airway inflammation that can be easily assessed in occupational field work, may be suitable for the evaluation of both short-term and long-term effects of preventive measures in occupational asthma.

Acute effects of hypertonic saline inhalation on nitric oxide pulmonary diffusing capacity in healthy adults.

We investigated acute effects of inhalation of hypertonic saline solution (HSS) and oxygen (O2, control exposure) on pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO). In a randomized crossover study, 20 healthy, non-smoking subjects were allocated to short-term inhalation of HSS or O2. Spirometry [(forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] and combined single-breath DLNO-DLCO measurements were performed before and immediately after inhalation of either HSS or O2. Percent changes were presented as median values (interquartile range). After HSS inhalation, DLNO, FEV1 and FVC were decreased by -3.0% (-7.3, 0.5), -3.1% (-4.2, -1.6) and -1.2% (-3.3, 0.6), respectively (all P < 0.05), without significant effect on DLCO. No changes in spirometry and diffusing capacity were observed following O2 inhalation. Acute inhalation of HSS causes a slight decrease in membrane conductance, probably as a result of fluid imbalance at the alveolar surface and interstitial fluid accumulation, both of which could impair gas exchange.

Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects.

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s-1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

[Acute effects on the health of children after accidental exposure to epichlorohydrine]. / Akute gesundheitliche Effekte bei Kindern nach einer akzidentellen Freisetzung von Epichlorhydrin.

PURPOSE: In September 2002, two freight trains collided at Bad Muender, Germany. The inhabitants were potentially exposed to combustion products and to the human carcinogen epichlorohydrine (ECH). We aimed to describe the geographical distribution of and potential risk factors for acute symptoms among children residing in Bad Muender. METHODS: The parents of a random sample of children were invited to answer a mail-in questionnaire (response rate 63%). The main outcome measures were self-reported acute symptoms potentially associated with combustion products (e. g., irritation of the eyes, nose, or throat) and stress-related unspecific symptoms (e. g., gastrointestinal complaints, sleep problems, headaches). The main location during the first 26 hours after the train accident served as exposure proxy measure. In addition, potential predictors for the symptoms under study were assessed. RESULTS: The prevalence of symptoms associated with combustion products was 5.9%. Unspecific symptoms were reported for 6.3% of the children. Main location and prevalence of symptoms were not significantly associated. Physician-diagnosed asthma and nasal allergies were the main predictors of symptoms. CONCLUSION: The prevalence of acute symptoms was relatively high in a random sample of children living close to the incident. However, associations between exposure to the accident and symptoms could not be established conclusively.

Toxoplasma gondii infection, atopy and autoimmune disease.

While for many allergens a dose-response relationship has clearly been established the association between early childhood exposure to cat allergens and risk of sensitisation is still controversial and even inverse relations have been described. At the same time, a negative association between Toxoplasma gondii (T. gondii) infection and atopic diseases has been found in epidemiologic studies. As cats are the major source of T. gondii oocysts, we hypothesize that cat allergen exposure might be a confounder in the association between T. gondii infection and allergic diseases. Furthermore, it is well known that atopic diseases are T helper cell 2 (Th2) driven while autoimmune diseases are dominated by a Th1 response. A counterbalance between Th1 and Th2 cells has been postulated. However, it has been shown recently that subjects with autoimmune disease are more likely to suffer from atopic diseases. Therefore, similar cytokine profiles might underlie these disorders. If this holds true it can be hypothesised that T. gondii infection is associated with a lower prevalence of autoimmune disease.

[The effects and properties of sodium nucleinate as a pyrogen working-standard. 9. Pyrogen detection with epinephrine-skin-, dactinomycin- and LAL-tests. The suitability of sodium nucleinate as a pyrogen standard]. / Uber Wirkungen und Eigenschaften des als Pyrogen-Arbeitsstandard verwendeten Natriumnucleinats. 9. Mitteilung: Pyrogennachweis mit Epinephrin-Haut-, Dactinomycin- und LAL-Test/Zur Eignung des Natriumnucleinats als Pyrogen-Standard.

Sodium nucleinate (NN) as well as bacterial lipopolysaccharide (LPS) can be detected by epinephrine-skin, dactinomycin and LAL tests. In the quantitative determination of two pyrogen standards for rabbit tests, consisting of NN, a smaller value was found by LAL test for the standard of greatest pyrogenic effect than for that less pyrogenically effective in rabbits. A standard consisting of NN can be used for the pyrogen test in rabbits. But in the future, if necessary a standard consisting of endotoxin will be used, due to its better comparability of results obtained by LAL and rabbit tests.

[The effects and properties of sodium nucleinate as a pyrogen working standard. 5. Interactions between pyrogens and corticotropin]. / Uber Wirkungen und Eigenschaften des als Pyrogen-Arbeitsstandard verwendeten Natriumnucleinats. 5. Mitteilung: Interaktionen zwischen Pyrogenen und Corticotropin.

In rabbits, the simultaneous i.v. injection of corticotrophin (ACTH) and bacterial lipopolysaccharide or sodium nucleinate (NN), as well as ATCH application before and after administration of one of the two pyrogens, induces changes in the course of body temperature as compared with other animals injected only one of the pyrogens. Principal differences between the effect of a bacterial lipopolysaccharide and that of sodium nucleinate cannot be observed. At simultaneous pyrogen application, the administration of ACTH leads to a delayed occurrence of temperature increases. Prophylactic ACTH injection induces, if performed only 30 min before pyrogen application, a still greater delay of pyrogen-induced temperature increase, while pyrogens applied 2 h after administration of ACTH induce temperature increases almost immediately. If ACTH is administered after pyrogen application this will at first lead to a temperature reduction, to be followed by repeated increase of temperature so that as a rule temperature curves with two peaks develop. This is true irrespective of whether ACTH application is performed 30, 60, or 90 min after pyrogen administration. Orientation tests have shown that only a part of ACTH present in the test solution can be detected if the biological assay of ACTH is made using the method based on the determination of the ascorbic acid content in the suprarenal glands of prednisolone-treated rats and if one of the two pyrogens simultaneously is applied.

[Effects and properties of sodium nucleinate used as a pyrogen working standard. 4. Acquired tolerance in rabbits following repeated intravenous injections of sodium nucleinate]. / Uber Wirkungen und Eigenschaften des als Pyrogen-Arbeitsstandard verwendeten Natriumnucleinats. 4. Mitteilung: Untersuchungen zur Toleranzbildung bei Kaninchen nach wiederholter intravenöser Injektion von Natriumnucleinat.

In rabbits, the repeated i. v. injection of bacterial lipopolysaccharide very quickly induces partial pyrogen tolerance if the injections are made at intervals of 1d. Evidently, this tolerance is without effect on the temperature increases due to subsequent sodium nucleinate injections, i. e. there is no cross tolerance between the bacterial lipopolysaccharide used for comparison and sodium nucleinate. A repeated sodium nucleinate injection, if made at intervals of 1d, does not induce pyrogen tolerance either under the experimental conditions chosen. Evidently, the temperature increases due to subsequent injections of the bacterial lipopolysaccharide used for comparison are not affected by preceding sodium nucleinate injections.

[The actions and properties of sodium nucleinate used as a pyrogen working standard. 3. Changes in the leukocyte picture of rabbits following intravenous injection of sodium nucleinate]. / Uber Wirkungen und Eigenschaften des als Pyrogen-Arbeitsstandard verwendeten Natriumnucleinats. 3. Mitteilung: Anderungen des weissen Blutbildes von Kaninchen nach intravenöser Injektion von Natriumnucleinat.

In rabbits, the i.v. injection of a sodium nucleinate solution, like a solution of bacterial pyrogen administered in the same way, at first induces leucopenia, followed by leucocytosis. The fraction of pseudoeosinophiles increases, while that of lymphocytes decreases.

[The effects and properties of sodium nucleinate used as a pyrogen working standard. 7. Pyrogen removal by filtration and pyrogen destruction by steam sterilization]. / Uber Wirkungen und Eigenschaften des als Pyrogen-Arbeitsstandard verwendeten Natriumnucleinats. 7. Mitteilung: Pyrogenentfernung durch Filtration und Pyrogenzerstörung durch Dampfsterilisation.

Solutions containing bacterial lipopolysaccharides (P) and sodium nucleinate (NN) solutions filtered through cellulose asbestos filters became pyrogen free. But the filters, with respect to the pyrogenicity of these solutions, became earlier exhausted in case of NN than in case of P. A 12-min heating to 121 degrees C in the autoclave led to a significant lowering of pyrogenicity both in P- and in NN-solutions. After a 2-h heating in same conditions both P- and NN-solutions in the chosen ranges of concentration became pyrogen free.

[The effects and properties of sodium nucleinate as a pyrogen working standard. 8. Pyrogen adsorption to charcoal and plastic]. / Uber Wirkungen und Eigenschaften des als Pyrogen-Arbeitsstandard verwendeten Natriumnucleinats. 8. Mitteilung: Pyrogen-Adsorption durch Kohle und durch Plaste.

Not only solutions containing bacterial lipopolysaccharide (P) but also sodium nucleinate (NN) solutions can be made free from pyrogens by treatment with charcoal adsorbing the two pyrogens. When shaking P- and NN-containing solutions with polyethylene granulate, P and NN are also partly adsorbed to this granulate. NN adsorption is smaller than that of P, relative to the determined pyrogenicity of the solutions tested. It could be discussed if this difference could also be interpreted in a way that NN itself and not only a contamination of this substance with lipopolysaccharide is the reason for the pyrogenic effect.

[False positive and false negative results in testing for pyrogenic impurities]. / Falschpositive und falschnegative Resultate bei der Prüfung auf pyrogene Verunreinigungen.

Causes of the occurrence of pyrogenic impurities in injection and infusion preparations as well as false-positive and false-negative results possible in the pyrogen test are reported. Possibilities of excluding pyrogenic impurities in the preparations concerned and of avoiding false-positive and false-negative results in the pyrogen test are discussed.

[The effects and properties of sodium nucleinate as a pyrogen working standard. 6. Pyrogen inactivation by incubation with blood serum or blood plasma]. / Uber Wirkungen und Eigenschaften des als Pyrogen-Arbeitsstandard verwendeten Natriumnucleinats. 6. Mitteilung: Pyrogen-Inaktivierung durch Inkubation mit Blutserum bzw. Blutplasma.

The 24-h storage of horse serum at 4 degrees C to which bacterial lipopolysaccharide (P) or sodium nucleinate (NN) was added, did not change the pyrogenic effect of these mixtures. Even after 2-h incubation at 37 degrees C changes could not be clearly detected. 24-h incubation at 37 degrees C leads to a clear, but only in case of NN, statistically significant reduction of pyrogenic effect. 24-h incubation of human heparin plasma at 37 degrees C, to which P or NN was added, in both cases resulted in statistically significant reductions of pyrogenic effect. Thus, when incubated with horse serum or human heparin plasma, the pyrogenic effect of NN is reduced in principle as well as that of P treated in the same way.

[The microbial count of insulin multiple-dose containers]. / Uber den Keimgehalt angebrochener Insulin-Mehrdosenbehälter.

In accordance with the Pharmacopoeia of the GDR, from multiple-dose containers containing injection preparations with preservatives added such preparations may be repeatedly withdrawn up to 72 h after opening these containers. Exempted from this limitation are multiple-dose containers containing insulin injection preparations repeatedly used by diabetics for self-injections. Microbiological tests were to contribute to clearing the question whether the period of using these insulin multiple-dose containers can be provided to be maximally 30 d after first use.

[Resistance of yeast cells to plastics and elastics]. / Beitrag zur Verträglichkeitsprüfung von Gegenständen aus Plasten und Elasten unter Verwendung von Hefezellen.

For the investigation of plastics and elastics several sensitive biological methods are in use. In the Pharmacopeia of GDR, 2nd edition, a safety-test on isolated frogheart is prescribed for plastics and a safety-test on daphnia magna for elastics. Ionescu-Stoian had recommended a test using saccharomyces cerevisiae. We found a good conformity of the result given by this test with the results of the daphnia-test. On the other hand, the saccharomyces cerevisiae-test is much more sensitive than the test with isolated frogheart.