Effects of intestinal microflora and the environment on the development of asthma and allergy

The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.     

Is age at implant the only factor that counts? The influence of working memory on lexical and grammatical development in children with cochlear implants

In this study, we explored the influence of time factors (age at implant, time with cochlear implant and age), complex working memory and phonological short-term memory on lexical and grammatical development in congenitally deaf children with cochlear implants. Fifteen children (aged 5 years 4 months to 11 years 5 months) were examined with the use of several linguistic and cognitive measures after a minimum of 18 months of implant use. Phonological short-term memory was assessed with non-word repetition, where the percentage of correctly repeated consonants and vowels was counted. For the assessment of lexical acquisition. a novel word learning task was administered. Receptive and expressive grammar was tested. Our results corroborate earlier findings on the influence of phonological short-term memory on novel word learning. The percentage of vowels correctly produced in non-word repetition was more important in this group than age at implant, not only for novel word learning. but also for receptive and expressive grammar.     

Use of folic acid supplementation and risk for dizygotic twinning

BACKGROUND: An increase in dizygotic twinning rate after folic acid supplementation has previously been described, but in a recent study from China, no such effect was seen. AIMS: To further investigate the association between use of folic acid supplement and dizygotic twinning. STUDY DESIGN: Using the Swedish Medical Birth Registry, the rate of dizygotic twinning among infants of women who reported the use of folic acid was studied, taking a number of confounders into consideration. Comparisons were made with all women recorded in the register. OUTCOME MEASURE: Unlike-sexed twin pairs were used as representatives of dizygotic twinning. RESULTS: A number of confounders for the association between folic acid use and twinning were identified and taken into consideration. Women who were immigrants (who used less folic acid and had slightly lower twinning rates than women born in Sweden) and women who reported subfertility problems or treatment for subfertility (who had a high use of folic acid and a high twinning rate) were excluded, and adjustment was then made for year of birth, maternal age, parity, and smoking in early pregnancy. Folic acid use and twinning risk increased with maternal age and decreased with parity. Smokers used less folic acid than nonsmokers. Concomitant use of other drugs was no important confounder except for those used at subfertility. The odds ratio (OR) for dizygotic twinning after folic acid supplementation was then 1.71 (95%CI=1.21-2.42) and for the years 2000-2001 even 2.09 (95%CI=1.39-3.12). CONCLUSION: There is an increase in twinning rate after folic acid supplementation in a Western population which should be taken into consideration when folic acid supplementation or food fortification is recommended.     

Premature death among teenage mothers

OBJECTIVE: Some data suggest an association between teenage childbearing and premature death. Whether this possible increase in risk is associated with social circumstances before or after childbirth is not known. We studied premature death in relation to age at first birth, social background and social situation after first birth. DESIGN: Population-based cohort study. SETTING: Women born in Sweden registered in the 1985 Swedish Population Census. POPULATION: Swedish women born 1950-1964 who had their first infant before the age of 30 years (N= 460,434). METHODS: Information on the women's social background and social situation after first birth was obtained from Population Censuses. The women were followed up with regard to cause of death from December 1, 1990 to December 31, 1995. Mortality rate ratios and 95% confidence intervals (CI) were calculated. MAIN OUTCOME MEASURES: Mortality rates by cause of death. RESULTS: Independent of socio-economic background, teenage mothers faced an increased risk of premature death later in life compared with older mothers (rate ratio 1.6, 95% CI 1.4-1.9). The increased risk was most evident for deaths from cervical cancer, lung cancer, ischaemic heart disease, suicide, inflicted violence and alcohol-related diseases. Some, but not all, of these increases in risk were associated with the poorer social position of teenagers mothers. CONCLUSIONS: Teenage mothers, independent of socio-economic background, face an increased risk of premature death. Strategies to reduce teenage childbearing are likely to contribute to improved maternal and infant health.     

Statistical methods for clinical verification of dose-response parameters related to esophageal stricture and AVM obliteration from radiotherapy

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and chi2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.     

Relation between oculo-auriculo-vertebral (OAV) dysplasia and three other non-random associations of malformations (VATER, CHARGE, and OEIS)

Using a statistical methodology, we aimed to identify a group of probable cases of oculo-auriculo-vertebral (OAV) dysplasia and to investigate possible relationships between different patterns of congenital malformations. Among 5,260 infants with multiple malformations collected from 4 large registers of congenital malformations, we identified 312 probable OAV cases. With the same technique, we have earlier defined epidemiological delineations of three other well-known non-random associations of congenital malformations (CHARGE, VATER, and OEIS). We found convincing relationships between OAV and VATER or CHARGE but none between OAV and OEIS or between the three malformation complexes CHARGE, VATER, and OEIS. An association between two conditions indicates similarities in pathogenesis or in etiology. We suggest that the connection between OAV and CHARGE could be related to a common pathogenetic mechanism: disturbed neural crest development.     

IL-6 levels in acute and post myocardial infarction: their relation to CRP levels, infarction size, left ventricular systolic function, and heart failure

BACKGROUND: Inflammatory mechanisms in heart disease are of great interest. The proinflammatory cytokine interleukin (IL) 6 has been linked to increased morbidity in unstable angina pectoris and depressed myocardial function in heart failure (HF). METHODS: We studied the relation of IL-6 levels to C-reactive protein (CRP), infarction size, left ventricular function, and HF in acute myocardial infarction (MI) and after hospital discharge in 31 consecutive patients (19 males, mean age 69+/-13 years). Blood sampling for IL-6 was performed on admittance, four times on day 1, twice on day 2, and once daily on days 3-5, and 6 and 12 weeks later. Clinical signs of HF were evaluated daily during hospitalization and after 6 and 12 weeks. Echocardiography was performed on day 3 and at 6 weeks. RESULTS: IL-6 showed a curved time course with elevated levels already on admittance (mean+/-S.D. 19.3+/-26.9 ng/l), thereafter increasing to a peak on days 1 and 2 (maximum 68.5+/-152.9 ng/l), and then declining rapidly to lower, although not normalized, levels during hospitalization and at 6 and 12 weeks. CRP showed a similar time pattern, but with a later peak and a seemingly less rapid decline in levels. Mean levels of IL-6 and CRP on days 1-5 correlated highly (r=0.794, p<0.0001). IL-6 and infarction size did not correlate. HF during hospitalization and at 6 weeks was not related to IL-6; however, patients with HF at 12 weeks had higher IL-6 levels, both at 6 and 12 weeks. Patients on ACE inhibitors or diuretics at discharge had higher IL-6 levels at 6 weeks. IL-6 during hospitalization was not related to LVF; yet, patients with depressed LVF in the hospital and at 6 weeks had higher IL-6 levels at 6 and 12 weeks. CONCLUSIONS: IL-6 in acute MI shows a curved time course and is highly correlated to CRP. It peaks on days 1 and 2 and remains elevated even after 12 weeks. Increased IL-6 levels after hospital discharge are associated with HF and depressed LVF. Whether anti-inflammatory agents will influence left ventricular dysfunction and outcome postacute MI has yet to be determined.