Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II).

BACKGROUND: Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent. OBJECTIVES: To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries. METHODS: Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi-centre cross-sectional study of 840 children aged 9-12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end-points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen-specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure. RESULTS: Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29-0.96) for endotoxin levels per m(2) of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64-0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever. CONCLUSION: These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.

Prevalence of self-reported food allergy and IgE antibodies to food allergens in Swedish and Estonian schoolchildren.

OBJECTIVE: To compare the prevalence of self-reported food allergy and IgE antibodies to food allergens in wheezing and non-wheezing Estonian and Swedish schoolchildren, in the light of the disparities in the standard of living, food consumption and prevalence of respiratory allergies that still exist between Estonia and the Scandinavian countries. DESIGN AND SETTING: As a part of the ISAAC Phase II study, children from a random sample of schools in Tallinn in Estonia and Linköping and Ostersund in Sweden participated in skin prick tests to inhalant allergens and the parents replied to questionnaires. IgE antibodies against a panel of food allergens (egg white, milk, soy bean, fish, wheat and peanut) were taken from children with questionnaire-reported wheezing and a random sample of nonwheezing children. SUBJECTS: Children aged 10-11 y. RESULTS: The prevalence of self-reported food allergy was similar in Estonia and Sweden and about twice as high in wheezing children than in nonwheezing children. In Estonia, however, 3% of the children with perceived food allergy reported reactions from at least four different foods, as compared to 31% in Sweden. The prevalence of sensitisation to food allergens was similar in wheezing and nonwheezing children in Estonia (8%) while, in Swedish children, IgE antibodies to food allergens were more likely among wheezing children (Linköping 38 vs 11%, crude OR 5.1, 95% CI 2.2-11.6, and Ostersund 24 vs 7%, crude OR 4.1, 95% CI 1.9-8.5). CONCLUSION: Our study suggests that IgE-mediated food reactions were less likely in Estonian schoolchildren. Moreover, the perception of food allergy and thereby the meaning of self-reported food allergy appears to be different in the two countries.

High body mass index, asthma and allergy in Swedish schoolchildren participating in the International Study of Asthma and Allergies in Childhood: Phase II.

AIM: To assess the relationship between high body mass index (BMI) and asthma and atopic manifestations in 12-y-old children. METHODS: The relationship between high BMI and asthma symptoms was studied in 457 sixth-grade children, with (n = 161) and without (n = 296) current wheeze. High BMI was defined as > or = 75th percentile of gender-specific BMI reference values for Swedish children at 12 y of age; overweight as a subgroup of high BMI was defined as > or = 95th percentile. Children with a BMI < 75th percentile served as controls. Questionnaires were used to assess asthmatic and allergic symptoms, and bronchial hyperresponsiveness was assessed by hypertonic saline provocation tests. RESULTS: Current wheeze was associated with high BMI after adjustment for confounding factors (adjusted OR 1.7, 95% CI 1.0-2.5) and overweight had an even more pronounced effect (adjusted OR 1.9, 95% CI 1.0-3.6). In addition, asthma severity was associated with high BMI, as evaluated by the number of wheezing episodes during the previous 12 mo among the wheezing children (adjusted OR 2.0, 95% CI 1.0-4.0). There was also an association between high BMI and the presence of eczema in wheezing children (adjusted OR 2.2, 95% CI 1.0-4.6). However, high BMI was not significantly associated with hay fever, positive skin prick tests or bronchial hyperresponsiveness. CONCLUSION: The study confirms and extends a previously observed relationship between BMI and the presence of wheezing and asthma.

Effects of lipopolysaccharide and phenylbutazone on gastric contents in the horse.

REASONS FOR PERFORMING STUDY: Endotoxaemia causes a disruption of gastrointestinal motility in the horse but there is no information on its effects on gastric secretion. Lipopolysaccharide (LPS) administration is known to affect gastric secretion in other species. HYPOTHESIS: That LPS, a toxic component of Gram-negative bacteria, would reduce gastric acid secretion and that pretreatment with phenylbutazone (PBZ) would block the effects of LPS. METHODS: The effects of LPS and PBZ on gastric contents were investigated in fasted, mature horses, with permanent gastric cannulae. Horses were pretreated with either saline or PBZ 15 mins before a 60 min infusion of either LPS or saline. Gastric contents were collected at 15 min intervals for 3 h, beginning 15 mins after the start of the LPS or saline infusion. RESULTS: Lipopolysaccharide significantly decreased gastric acid output, [K+] and potassium output and increased [Na+] and sodium output. Phenylbutazone did not affect basal gastric acid secretion but decreased LPS-induced changes in the secreted volume, [Na+] and sodium output. CONCLUSIONS: This study provides evidence that LPS affects gastric acid secretion in the horse and that these LPS-induced changes are mediated, in part, by prostaglandins. POTENTIAL RELEVANCE: Lipopolysaccharide administration can induce changes in the composition of gastric contents in the horse but further work is needed to determine the source of these changes.

Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren.

BACKGROUND: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. OBJECTIVE: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. METHODS: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Linköping (n = 911) and Ostersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. RESULTS: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in Ostersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Linköping and 58% in Ostersund) bronchial hyper-responsiveness (BHR) (48% in Linköping and Ostersund) and anti-asthmatic treatment (63% in Linköping and 81% in Ostersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (Ostersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. CONCLUSIONS: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

Atopy among schoolchildren in northern and southern Sweden in relation to pet ownership and early life events.

Studies have suggested a higher prevalence of asthma and allergies in northern, as compared to southern, Scandinavia. The aim of this study was to evaluate regional differences in atopy in relation to pet ownership and certain early life events among schoolchildren (n=2108) aged 10-11 years from Linköping in southern Sweden and Ostersund in northern Sweden. The parents completed a questionnaire, comprising questions on home environment, heredity, socio-economic conditions, and the core questions on symptoms from the International Study of Asthma and Allergies in Childhood. The children were skin-prick tested to eight common inhalant allergens. Information on maternal smoking habits, gestational age, and anthropometric measures were obtained from the Swedish Medical Birth Registry. The prevalence of atopic symptoms and sensitization to pollen were similar in Ostersund and in Linköping. A higher prevalence of sensitization to animal dander among children in Ostersund could be linked to a higher occurrence of pets in the community. Current cat ownership was related to less sensitivity to cat allergen but only in children with an atopic heredity. Ponderal index >30 kg/m3 was related to an increased risk of atopic sensitization, both in Linköping (adjusted odds ratio 2.1; 95% confidence interval 1.1-4.0) and in Ostersund (adjusted odds ratio 2.0; 95% confidence interval 1.1-3.5). Maternal smoking during pregnancy was related to an increased risk of atopic sensitization among children in Linköping, whereas current smoking was associated with a decreased risk of sensitization in Ostersund. In conclusion, we demonstrated that a high occurrence of pets in the community was associated with sensitization, whereas atopic symptoms were essentially unaffected. This study has also suggested an association between body size at birth and atopic sensitization at 10-11 years of age.

Microflora-associated characteristics in faeces from allergic and nonallergic infants.

BACKGROUND: The prevalence of allergic diseases has increased particularly over the past 30-40 years. A reduced microbial stimulation during infancy may result in a development of a disturbed balance between Th1- and Th2-like immunity. The gut flora is, quantitatively, the most important source for such stimulation. OBJECTIVE: The aim of the study was to compare the gut microbial flora in 25 allergic and 47 nonallergic 13-month-old infants (range 11-18), through analysing microflora-associated biochemical markers in faeces. METHODS: Microflora associated characteristics (MACs) were assessed by determining the concentrations of eight different short chain fatty acids and the conversion of cholesterol to coprostanol by gas chromatography. Faecal tryptic activity was analysed spectrophotometrically. RESULTS: The allergic infants had lower levels of propionic, i-butyric, butyric, i-valeric and valeric acid. In contrast, they had higher levels of the rarely detected i-caproic acid, which has been associated with the presence of Clostridium difficile. Furthermore, the allergic infants had higher relative distribution of acetic and i-caproic acid. None of the other parameters differed between the groups. CONCLUSION: The results demonstrate differences in the MACs between allergic and nonallergic infants, indicating differences in the composition of the gut flora that may disturb the development of a normal Th1-/Th2-balance in allergic children.

Effect of nervous excitation on acid secretion in horses.

Nervous excitation was induced by various means in horses provided with a gastric cannula. Insulin hypoglycaemia profoundly inhibited the basal acid output and volume secreted from the stomach. No clear effect on acid secretion was noted after administration of bethanechol, as the acid output was covered by the copious secretion of saliva. Atropine almost abolished the basal acid output. Sensoric stimulation by teasing caused a slight but not significant increase in the total acid output. These data suggest that cholinergic excitation might play a role in the stimulation of both volume and acid secretion in the horse. The inhibitory effect seen on these two parameters after insulin hypoglycaemia may hypothetically be ascribed to inhibitory impulses carried in peptide neurones of the vagal nerves or to inhibitory impulses in adrenergic nerves acting directly or indirectly on the parietal cells.

Postmortem findings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924-1996).

The present study was performed to estimate retrospectively the prevalence of gastric ulceration in necropsied Swedish horses and to evaluate some potential risk factors. Horses (n = 3715) older than age one year and necropsied 1924-1996 were included. Information about breed, gender, age, season of death, clinical signs of colic, Gasterophilus larvae and documentation of diseases in different organs was recorded. Data on size, number and anatomical distribution of gastric ulcers were also obtained. The cold-blooded horses and the Standardbreds were the 2 most dominating breeds in our material. Gastric ulcers/erosions were seen in 633 (17%) of the horses. The highest prevalence was found in Thoroughbreds (19%) and Standardbreds (19%), whereas only 7% of the cold-blooded horses were affected. The cutaneous region along the margo plicatus was the most commonly affected area (52%). Multiple ulcers were seen in 62% of the horses with gastric ulcers and concurrent ulcers in the oesophagus were reported in 6%. In the bivariate analysis, significant associations were found between gastric ulcers and signs of colic (P<0.001) and gender (P<0.001), as well as between concomitant bowel (P<0.001), liver (P<0.05) and oesophageal (P<0.01) lesions. Using a multivariate logistic regression model, only year of necropsy and breed were found significantly to influence the risk of gastric ulceration by decreasing the Log Likelihood test value. The present study shows clearly that gastric ulceration has been present in Swedish horses throughout the 20th century, which also may be the situation worldwide.

Post-mortem findings of gastric ulcers in Swedish horses up to one year of age: a retrospective study 1924-1996.

Necropsy records from 702 horses, less than one year old, that were subjected to necropsy between 1924 and 1996 were used to estimate the prevalence of gastric ulceration in younger horses and to evaluate some potential risk factors that may contribute to the development of gastric ulceration. Information concerning breed, gender, age, season of death, clinical signs of colic, medical treatment, parasitism and documentation of diseases in different organs were recorded, as well as size, number and anatomical distribution of ulcers. Gastric ulcers were found in 96 of 702 young horses (14%) and gastritis in another 64 animals (9%). The cutaneous region adjacent to margo plicatus (51%), and the corpus region were commonly affected (46%). The investigation clearly demonstrates that gastric ulceration has affected young Swedish horses to a similar degree during most of the 20th century. A significant (p < or = 0.05) association between gastric ulcers and the signs of colic, parasitism and a concomitant intestinal, liver, and oesophageal involvement was found. No breed or sex predilection with gastric ulcers was obtained. The risk of gastric ulcers was highest during the fall (odds ratio 3.52) and lowest during the summer (odds ratio 0.45). The seasonal variation could not be explained by concomitant findings of Gasterophilus larvae. By using a multivariate logistic regression analysis, only season significantly influenced the risk of gastric ulceration.

Effects of intramuscular omeprazole on gastric acid secretion in horses over a twenty-four hour period.

The effect of intramuscular (i.m.) omeprazole (0.25 or 1.0 mg/kg bwt; LD and HD), respectively, on volume, total acid output (TAO) and pH of the gastric juice was studied during 24 h in 5 horses with a chronically implanted gastric cannula. Whether secretion in controls was basal or stimulated with pentagastrin (8 micrograms/kg bwt/h), volume (NS) and TAO (P < 0.01, NS) gradually decreased and pH increased (P < 0.05, NS). Omeprazole significantly reduced the average basal TAO by 49 +/- 6% (LD) and 88 +/- 3% (HD) and the stimulated TAO by 64 +/- 2% and 97 +/- 1%. Basal pH in controls was 2.1-4.2 and after omeprazole treatment, pH 2.8-4.1 (LD) and 2.4-6.6 (HD). After stimulation, the corresponding pH values were 2.6-3.3, 3.9-4.9 and 5.4-7.2. The biological availability of omeprazole was 70-80%. Due to the simplicity of the administration technique and the higher biological availability, intramuscular administration may offer a practical and less expensive way of treating gastric ulcers in horses.

Effects of differently composed feeds and physical stress on plasma gastrin concentration in horses.

Plasma gastrin concentrations were determined in 6 Standardbreds (4 geldings and 2 mares) after 3 different meals consisting of unlimited amounts of hay (8-9 kg per horse), a restricted amount of hay (0.6 kg/100 kg body-weight) and grain (0.2 kg/100 kg body-weight) in combination or of grain alone (0.2 kg/100 kg body-weight). In another series of experiments the possible role of gastrin as a stress hormone was investigated. Plasma gastrin and cortisol concentrations were determined during fasting and compared with concentrations during hay feeding. In addition, gastrin and cortisol concentrations were determined before, during and after 2 kinds of physical exercise on a treadmill. Meal stimulation significantly increased the plasma gastrin concentration, irrespective of the meal composition. An immediate and large increase in plasma gastrin concentration was found when voluminous meals were given, whereas a small meal evoked a later onset of gastrin release, suggesting that gastric distention plays an important role in inducing gastrin release during a meal. Meals consisting of grain seem to evoke a slower onset and then a more prolonged gastrin response than a hay meal, possibly due to different emptying rates of the stomach. Nervous excitation may play a minor role in the activation of gastrin release in horses. No experimental support was obtained for the idea that gastrin acts as a stress hormone in the horse.

Unique progastrin processing in equine G-cells suggests marginal tyrosyl sulfotransferase activity.

Previous studies have indicated that equine G-cell processing of progastrin differs from that of other species. Since the difference may be due to structural features, we have identified equine gastrin-17 and -34 (

Twenty-four-hour basal and repetitive pentagastrin-stimulated gastric acid secretion in normal and sham-operated rats and in rats after gonadectomy or treatment with estradiol or testosterone.

BACKGROUND: Studies in different species have suggested, but not established, that sex hormones influence gastric acid secretion. We studied how acid output is affected by the sex hormones estradiol or testosterone in vivo and in vitro. METHODS: In gastric fistula rats that were normal, sham-operated, neonatally gonadectomized, or treated with estradiol or testosterone, 24-h basal and pentagastrin-stimulated acid secretion was measured. The in vitro effects of estradiol and testosterone on histamine-induced aminopyrine accumulation in isolated parietal cells were also determined. RESULTS: Basal acid output was similar in the two sexes, but stimulated secretion was significantly higher (34%; P < 0.01) in males. Ovariectomy did not influence acid output, whereas orchidectomy reduced basal (18%; NS) and stimulated 24-h secretion (P < 0.01). Estradiol decreased (23%; NS) the 24-h basal output in females but not in males. Estradiol suppressed stimulated secretion in females (29%, P < 0.01) and males (42%, P < 0.01) during the day. At night the stimulated secretion increased in both females (17%, NS) and males (32%, P < 0.05). A similar pattern was found when rats were treated with testosterone. In vitro, estradiol and testosterone reduced histamine-stimulated aminopyrine accumulation in both female and male isolated parietal cells. CONCLUSIONS: Estradiol and testosterone both appear to influence gastric secretion in rats, and their action differs between day and night, between the sexes, and between basal and stimulated secretion.

In-vitro activity of teicoplanin and ceftriaxone in combination against pathogens involved in paediatric bone and joint infections.

We investigated the combination of teicoplanin and ceftriaxone for its bactericidal activity against Staphylococcus aureus, Haemophilus influenzae type b and Streptococcus pneumoniae isolated from bone and joint infections in children. An increase in bactericidal activity was observed against isolates of S. aureus and H. influenzae when the antibiotics were tested at fractional MICs whereas indifference was observed at their MICs. Similar results were obtained at fractional MICs against S.pneumoniae, but the bactericidal activity fell by more than 1 x log 10 cfu/mL when the antibiotics were tested at or above their MICs.

Killing activity of cefpirome against penicillin-resistant Streptococcus pneumoniae isolates from patients with meningitis in a pharmacodynamic model simulating the cerebrospinal fluid concentration profile.

An in vitro pharmacodynamic model was used to determine the killing kinetics of cefpirome against 20 Streptococcus pneumoniae strains (penicillin G MICs, > 0.125 to 2 micrograms/ml) isolated from patients with meningitis. The concentration of cefpirome was adjusted dynamically to simulate the median concentration profile obtained in the cerebrospinal fluid of adults after the infusion of a single dose of 2 g. The cefpirome MIC at which 90% of isolates are inhibited was 0.5 microgram/ml. Bactericidal activity was observed at 6 h, with mean killing of 3.51 +/- 0.34 log10 CFU/ml for all strains for which the cefpirome MIC was < 0.5 microgram/ml. In contrast, for strains for which the cefpirome MIC was > or = 0.5 microgram/ml, killing was significantly less (P < 0.05), with a mean reduction of only 2.86 +/- 0.57 log10 CFU/ml.