Effects of environmental tobacco smoke on the respiratory health of children

This review synthesizes current knowledge of the effects of prenatal and postnatal exposure to environmental tobacco smoke on the respiratory health of children. A Medline database search was conducted for 1966 through October 2000. Limited evidence was found that exposure in pregnancy influences fetal growth, increases the risk of preterm delivery, and predicts the development of asthma and reduced lung function later in life. Both occupational and home environments contribute to the exposure of pregnant women and thus indirectly to adverse effects on children. There is strong and consistent evidence that exposure in childhood causes chronic respiratory symptoms (eg, cough, phlegm, and wheezing) and induces asthma. Limited evidence supports the role of childhood exposure in the poor overall control of established disease. Postnatal exposure is likely to have a small adverse impact on lung function growth. Prenatal and postnatal exposures have an important impact on children's respiratory health. These effects are preventable if pregnant women and children are protected from exposure to environmental tobacco smoke.     

Evaluation of cocktail approach to standardise Caco-2 permeability experiments.

The purpose of this study was to investigate the suitability and reliability of n-in-one approach using FDA suggested compounds for standardising Caco-2 permeability experiments. Special attention was paid to the evaluation of rank order correlation and mechanistic insights of compound permeability. Transport studies with antipyrine, metoprolol, ketoprofen, verapamil, hydrochlorothiazide, ranitidine, mannitol and fluorescein were performed in 12- and 24-well formats, as single compounds and in cocktails under iso-pH 7.4 and pH-gradient (pH 5.5 vs. 7.4) conditions. Compounds were quantified using n-in-one LC/MS/MS analysis. The cocktail-dosing proved to be a feasible method to determine the permeability of the Caco-2 cell line and to introduce external standards for permeability tests. Even though sink conditions were lost in cocktail experiments for highly permeable compounds, the rank order of compound permeability and the classification to low and high permeability compounds remained unchanged between single and cocktail studies and permeability values of 12- and 24-well formats were directly comparable. Under pH-gradient conditions the margin between high and low permeability compounds was narrower due to the lower permeability (higher fraction of ionisation) of basic molecules. Of the compounds studied, antipyrine, metoprolol, hydrochlorothiazide and mannitol are suitable for evaluation and standardisation purposes of passive permeability, while fluorescein would function as paracellular marker under iso-pH 7.4. As efflux activity may vary between cell batches, verapamil is a useful marker for P-glycoprotein.     

Transient increase in procollagen propeptides in the CSF after subarachnoid hemorrhage

BACKGROUND: Meningeal fibrosis following subarachnoid hemorrhage (SAH) has been verified histologically in experimental animals and in human autopsy samples, but the clinical course of the intrathecal fibroproliferative reaction is unknown. The authors therefore studied time-related changes in the CSF concentrations of type I (PICP) and type III (PIIINP) procollagen propeptides in patients with recent SAH. Method: Fifty-two CSF samples were obtained from 39 patients with SAH treated surgically and eight samples from eight patients with SAH who were not surgically treated. The samples were analyzed for PICP and PIIINP by using radioimmunoassays. RESULTS: The authors found a time-dependent increase in PICP and PIIINP in the CSF of the patients with SAH. Two weeks after the hemorrhage, concentrations were four times higher in patients with SAH than the concentrations in the control subjects. Concentrations in patients with SAH then declined steadily, but remained slightly but significantly elevated even at 10 weeks. PICP and PIIINP did not correlate with the age or sex of the patient or the amount of blood in the initial CT scan. Four patients developed late posthemorrhagic hydrocephalus; their PICP and PIIINP levels were higher than in matched patients with SAH without hydrocephalus. CONCLUSIONS: Time-dependent changes in CSF concentrations of PICP and PIIINP suggest a transient fibroproliferative reaction in the meninges after SAH. The considerable magnitude and extended time course of the changes make the measurement of PICP and PIIINP practicable for the diagnosis of a fibroproliferative state in patients with recent meningeal disease. Furthermore, the results suggest a role for meningeal fibrosis in the development of late posthemorrhagic hydrocephalus.     

The effects of gender and age on the colonoscopic examination

The data concerning the influence of gender and age on a patient's toleration of and the technical difficulty of colonoscopy are conflicting. One hundred eighty patients (108 women and 72 men) undergoing colonoscopy were categorized into three age groups: the young (aged 2040 years), the middle-aged (aged 41-60 years), and the old (aged 61-75 years). The endoscopists assessed the examination immediately after the procedure. The patients completed a questionnaire before leaving the endoscopy unit and again 2 weeks later. The women rated colonoscopy after the procedure more painful (p < 0.01) and in the repeat questionnaire more painful (p < 0.05) and more difficult (p < 0.05) than men. Also, the endoscopists judged colonoscopy to be more difficult (p < 0.001) and the time taken to reach cecum longer (p < 0.01) for women. The young experienced more discomfort than the middle-aged or the old, as evaluated after the procedure (p < 0.05). In the repeat questionnaire, the young reported more discomfort and pain than the middle-aged (p < 0.05). The endoscopists also judged the examination to be more difficult and the time taken to intubate cecum longer for the old than for the middle-aged (p < 0.05) or the young (p < 0.01). Correspondingly, the examination time was shorter among the young when compared with the middle-aged (p < 0.05) or the old (p < 0.001). The young were least willing to repeat the examination (p < 0.05). Colonoscopy is less tolerable and more difficult for women. Although colonoscopy among the old patients was technically more difficult, they tolerated the procedure better than the young.     

Free secretory component as a standardization protein for nasopharyngeal specimens from children with upper respiratory tract infection

Free secretory component (FSC) has been recommended as a reliable protein for correction of the unknown dilution in tracheal aspirate samples from preterm infants. To investigate whether FSC would also provide a valid standardization protein for samples of nasopharyngeal secretions, this study determined the intersubject variation and the alteration over time in the concentrations of FSC in nasal secretions from 35 children (median age 14 months) who participated in an antibiotic efficacy trial. Nasopharyngeal aspirates were obtained at enrolment and after 2-3 d. FSC in the specimens was quantified by a direct enzyme immunoassay. The concentrations of FSC in the nasal secretions ranged from 0.08 to 189.6 μg ml^-1 (median 12.3 μg ml^-1); the ratio of the highest to the lowest concentrations was 2370, the difference between the 90th and 10th percentile concentrations was 189-fold and the difference between the 75th and 25th percentile values was 26. FSC concentrations were significantly lower in children aged ≤12 months (median 2.2 μg ml^-1) than in the older children (median 21.5 μg ml^-1; p = 0.035). Between the first and the follow-up specimens, 65% of the children had ≥2-fold difference in the levels of FSC in the secretions. Because an optimal standardization protein should show minimal variation between individuals and over time, FSC may not be a suitable protein for correction of the unknown dilution of nasopharyngeal specimens from children with upper respiratory tract infection.     

Pharmacological properties, central nervous system effects, and potential therapeutic applications of atipamezole, a selective alpha2-adrenoceptor antagonist

Atipamezole is an alpha2-adrenoceptor antagonist with an imidazole structure. Receptor binding studies indicate that its affinity for alpha2-adrenoceptors and its alpha2/alpha1 selectivity ratio are considerably higher than those of yohimbine, the prototype alpha2-adrenoceptor antagonist. Atipamezole is not selective for subtypes of alpha2-adrenoceptors. Unlike many other alpha2-adrenoceptor antagonists, it has negligible affinity for 5-HT1A and I2 binding sites. Atipamezole is rapidly absorbed and distributed from the periphery to the central nervous system. In humans, atipamezole at doses up to 30 mg/subject produced no cardiovascular or subjective side effects, while at a high dose (100 mg/subject) it produced subjective symptoms, such as motor restlessness, and an increase in blood pressure. Atipamezole rapidly reverses sedation/anesthesia induced by alpha2-adrenoceptor agonists. Due to this property, atipamezole is commonly used by veterinarians to awaken animals from sedation/anesthesia induced by alpha2-adrenoceptor agonists alone or in combination with various anesthetics. Atipamezole increased sexual activity in rats and monkeys. In animals with sustained nociception, atipamezole increased pain-related responses by blocking the noradrenergic feedback inhibition of pain. In tests assessing cognitive functions, atipamezole at low doses has beneficial effects on alertness, selective attention, planning, learning, and recall in experimental animals, but not necessarily on short-term working memory. At higher doses atipamezole impaired performance in tests of cognitive functions, probably due to noradrenergic overactivity. Recent experimental animal studies suggest that atipamezole might have beneficial effects in the recovery from brain damage and might potentiate the anti-Parkinsonian effects of dopaminergic drugs. In phase I studies atipamezole has been well tolerated by human subjects.     

Home dampness and molds, parental atopy, and asthma in childhood: a six-year population-based cohort study

Previous studies of how parental atopy and exposure to dampness and molds contribute to the risk of asthma have been mainly cross-sectional or prevalent case-control studies, where selection and information bias and temporality constitute problems. We assessed longitudinally the independent and joint effects of parental atopy and exposure to molds in dwellings on the development of asthma in childhood. We conducted a population-based, 6-year prospective cohort study of 1,984 children 1-7 years of age at the baseline in 1991 (follow-up rate, 77%). The study population included 1,916 children without asthma at baseline and complete outcome information. The data collection included a baseline and follow-up survey. The outcome of interest was development of asthma during the study period. The studied determinants were parental allergic diseases and four indicators of exposure at baseline: histories of water damage, presence of moisture and visible molds, and perceived mold odor in the home. A total of 138 (7.2%) children developed asthma during the study period, resulting in an incidence rate of 125 cases per 10,000 person-years [95% confidence interval (CI), 104-146]. In Poisson regression adjusting for confounding, parental atopy [adjusted incidence rate ratio (IRR) 1.52; 95% CI, 1.08-2.13] and the presence of mold odor in the home reported at baseline (adjusted IRR 2.44; 95% CI, 1.07-5.60) were independent determinants of asthma incidence, but no apparent interaction was observed. The results of this cohort study with assessment of exposure before the onset of asthma strengthen the evidence on the independent effects of parental atopy and exposure to molds on the development of asthma.     

Socio-economic position and its relationship to physical capacity among elderly people living in Jyväskylä, Finland: five- and ten-year follow-up studies

Socio-economic differences in self-reported disability are well described but much less is known about their associations with more objective measures of physical capacity. The aim was to study socio-economic differences in performance-based physical capacity in 75-year-old persons, examining changes in performance at five- and ten-year follow-up intervals. At the baseline 350 residents of the city of Jyv?skyl?, Finland, aged 75 were interviewed and 295 of them took part in clinical examinations. The corresponding figures at the five-year follow-up were 234 and 191 and at the ten-year follow-up 139 and 103. The statistical significance of differences in physical capacity between the socio-economic groups and genders were tested using ANOVA in univariate and repeated measures models and ANCOVA, with confounders added to the models. Generally, higher education and income were separately related to better maximal walking speed and vital capacity at every measurement point. In addition, higher income was related to better maximal isometric hand grip strength at both follow-ups. When education and income were in the same model, only income was related to physical capacity, almost without exception. Similarly, in the five- and ten-year follow-up periods, both education and income groups showed a parallel decline in physical capacity. The association between income and physical capacity remained even after adjusting for smoking, physical activity and number of chronic diseases. The results indicate that elderly people in disadvantaged socio-economic groups show lower levels of performance in almost all domains of physical capacity, but change in capacity over time does not differ significantly between either markers of socio-economic position.