Safety of tacrolimus 0.03% and 0.1% ointments in young children with atopic dermatitis: a 36-month follow-up study.

BACKGROUND: Topical tacrolimus is used off-label in young children, but data are limited on its use in children under 2 years of age and for long-term treatment. AIM: To compare safety differences between topical tacrolimus (0.03% and 0.1% ointments) and topical corticosteroids (mild and moderate potency) in young children with atopic dermatitis (AD). METHODS: We conducted a 36-month follow-up study with 152 young children aged 1-3 years with moderate to severe AD. The children were followed up prospectively, and data were collected on infections, disease severity, growth parameters, vaccination responses and other relevant laboratory tests were gathered. RESULTS: There were no significant differences between the treatment groups for skin-related infections (SRIs) (P = 0.20), non-SRIs (P = 0.20), growth parameters height (P = 0.60), body weight (P = 0.81), Eczema Area and Severity Index (EASI) (P = 0.19), vaccination responses (P = 0.62), serum cortisone levels (P = 0.23) or serum levels of interleukin (IL)-4, IL-10, IL-12, IL-31 and interferon-γ. EASI decreased significantly in both groups (P < 0.001). In the tacrolimus group, nine patients (11.68%) had detectable tacrolimus blood concentrations at the 1-week visit. There were no malignancies or severe infections during the study, and blood eosinophil counts were similar in both groups. CONCLUSIONS: Topical tacrolimus (0.03% and 0.1%) and topical corticosteroids (mild and moderate potency) are safe to use in young children with moderate to severe AD, and have comparable efficacy and safety profiles.

Infant and childhood growth and frailty in old age: the Helsinki Birth Cohort Study.

BACKGROUND: Evidence from life course studies highlights the importance of infant and childhood growth as risk factors for adulthood chronic diseases. METHODS: In this sub-study of the Helsinki Birth Cohort Study, we studied 1078 individuals who had both information on body size from birth to 12 years of age and who were assessed for frailty according to the Fried criteria at the mean age of 71 years. RESULTS: Greater BMI gain between 2 and 11 years in boys was associated with frailty in old age (age-adjusted RRR 2.36, 95% CI 1.21, 4.63). No similar associations were observed in girls. CONCLUSIONS: Men who were frail in old age experienced accelerated BMI gain in childhood compared with those men who were not frail. This was not observed in women, which suggests that the patterns of early growth predisposing to frailty may vary by sex.

Early life determinants of frailty in old age: the Helsinki Birth Cohort Study.

BACKGROUND: there is evidence suggesting that several chronic diseases have their origins in utero and that development taking place during sensitive periods may affect the aging process. We investigated whether early life determinants would be associated with frailty in old age. METHODS: at a mean age of 71 years, 1,078 participants belonging to the Helsinki Birth Cohort Study were assessed for frailty according to the Fried frailty criteria. Early life measurements (birth weight, length, mother body mass index [BMI] and parity) were obtained from birth, child welfare and school health records. Multinomial regression analysis was used to assess the association between early life determinants and frailty in old age. RESULTS: weight, length and BMI at birth were all inversely associated with frailty in old age. A 1 kg increase in birth weight was associated with a lower relative risk ratio (RRR) of frailty (age and sex-adjusted RRR = 0.40, 95% CI: 0.19, 0.82) compared to non-frailty. Associations persisted after adjusting for several confounding factors. Compared to cohort members in the upper middle class, those who as adults worked as manual workers or belonged to the lower middle class, were at an increased risk of frailty. CONCLUSIONS: those who were small at birth were at an increased risk of developing frailty in old age, suggesting that frailty is at least partly programmed in early life. A less privileged socioeconomic status in adulthood was associated with an increased risk of frailty in old age.

Early life stress and frailty in old age: the Helsinki birth cohort study.

BACKGROUND: Evidence suggests that early life stress (ELS) may extend its effect into adulthood and predispose an individual to adverse health outcomes. We investigated whether wartime parental separation, an indicator of severe ELS, would be associated with frailty in old age. METHODS: Of the 972 participants belonging to the present sub-study of the Helsinki Birth Cohort Study, 117 (12.0%) had been evacuated abroad unaccompanied by their parents in childhood during World War II. Frailty was assessed at a mean age of 71 years according to Fried's criteria. RESULTS: Thirteen frail men (4 separated and 9 non-separated) and 20 frail women (2 separated and 18 non-separated) were identified. Compared to the non-separated men, men who had been separated had an increased relative risk ratio (RRR) of frailty (age-adjusted RRR 3.93, 95% CI 1.02, 15.11) that persisted after adjusting for several confounders. No associations were observed among women (RRR 0.62; 95% CI 0.13, 2.94). CONCLUSIONS: These preliminary results suggest that ELS might extend its effects not just into adulthood but also into old age, and secondly, that men may be more vulnerable to the long-term effects of ELS.

Associations between family characteristics and parental empowerment in the family, family service situations and the family service system.

BACKGROUND: Parental empowerment signifies parents' sense of confidence in managing their children, interacting with services that their children use and improving child care services. High empowerment is associated with parents' resilience to demands and their confidence to make decisions and take actions that positively affect their families. Most families with children access various healthcare and education services. Professionals working in these services are therefore ideally placed to reinforce parental empowerment. However, little is known about the characteristics associated with parental empowerment within a generic sample of parents or in the context of basic child care services. AIM: The aim of this study was to assess how family characteristics are associated with maternal and paternal empowerment in the family, in service situations and in the service system. METHOD: Parental empowerment was measured among 955 parents (mothers = 571; fathers = 384) of children aged 0-9 years using the Generic Family Empowerment Scale. Family characteristics were assessed through questions on children, parents and the life situation. Associations between empowerment and family characteristics were evaluated using one-way analysis of variance and t-test. Parental empowerment was predicted by multiple linear regression analysis. RESULTS: Parents' concerns related to their parenting, such as whether they possessed sufficient skills as a parent or losing their temper with children, as well as experiences of stress in everyday life, were negatively associated with all dimensions of maternal and paternal empowerment. Both determinants were more common and more significant in empowerment than child-related problems. CONCLUSION: Promoting parental self-confidence and providing appropriate emotional and concrete support for everyday functioning may reinforce parental empowerment, thereby enhancing families' well-being and coping, as well as improving their access to required services and timely support. Finally, it may facilitate the provision of better services to all families.

Identifying microRNAs regulating B7-H3 in breast cancer: the clinical impact of microRNA-29c.

BACKGROUND: B7-H3, an immunoregulatory protein, is overexpressed in several cancers and is often associated with metastasis and poor prognosis. Here, our aim was to identify microRNAs (miRNAs) regulating B7-H3 and assess their potential prognostic implications in breast cancer. METHODS: MicroRNAs targeting B7-H3 were identified by transfecting two breast cancer cell lines with a library of 810 miRNA mimics and quantifying changes of B7-H3 protein levels using protein lysate microarrays. For validations we used western immunoblotting and 3'-UTR luciferase assays. Clinical significance of the miRNAs was assayed by analysing whether their expression levels correlated with outcome in two cohorts of breast cancer patients (142 and 81 patients). RESULTS: We identified nearly 50 miRNAs that downregulated B7-H3 protein levels. Western immunoblotting validated the impact of the 20 most effective miRNAs. Thirteen miRNAs (miR-214, miR-363*, miR-326, miR-940, miR-29c, miR-665, miR-34b*, miR-708, miR-601, miR-124a, miR-380-5p, miR-885-3p, and miR-593) targeted B7-H3 directly by binding to its 3'-UTR region. Finally, high expression of miR-29c was associated with a significant reduced risk of dying from breast cancer in both cohorts. CONCLUSIONS: We identified miRNAs efficiently downregulating B7-H3 expression. The expression of miR-29c correlated with survival in breast cancer patients, suggesting a tumour suppressive role for this miRNA.

The validity and reliability of the Finnish Family Empowerment Scale (FES): a survey of parents with small children.

BACKGROUND: The Family Empowerment Scale (FES) is a widely used instrument which measures the parents' own sense of their empowerment at the level of the family, service system and community. It was originally developed for parents of children with emotional disabilities. AIM: The aims of this study were to evaluate the validity and reliability of the Finnish FES and to examine its responsiveness in measuring the empowerment of parents with small children. METHODS AND PARTICIPANTS: The English FES was translated into Finnish using back translation and modified so as to be generic and convenient for all families. The construct, convergent, discriminant and concurrent validities, reliability and responsiveness of the Finnish FES were examined. Participants (n = 955) were the parents of children aged 0-9 years who had been selected using stratified random sampling. RESULTS: Confirmatory factor analysis proved that the Finnish FES had three subscales based on the original FES. Convergent and discriminant validities confirmed and supported the same construct. The relationship between parents' participation and empowerment was tested for concurrent validity. As in previous FES studies, the participating parents were more empowered, which supported the concurrent validity. The reliability of the Finnish FES proved acceptable for both parents. The Finnish FES could also discriminate the responses of the parents. Participation in the activities organized by the family service system influenced parents' perceptions of empowerment more than did their background characteristics. CONCLUSIONS: The Finnish FES is a valid and reliable instrument and it is suitable for measuring the empowerment of parents. However, it is necessary to consider how the FES would identify in the best way the parents who perhaps need some help.

An allele of COL9A2 associated with intervertebral disc disease.

Intervertebral disc disease is one of the most common musculoskeletal disorders. A number of environmental and anthropometric risk factors may contribute to it, and recent reports have suggested the importance of genetic factors as well. The COL9A2 gene, which codes for one of the polypeptide chains of collagen IX that is expressed in the intervertebral disc, was screened for sequence variations in individuals with intervertebral disc disease. The analysis identified a putative disease-causing sequence variation that converted a codon for glutamine to one for tryptophan in six out of the 157 individuals but in none of 174 controls. The tryptophan allele cosegregated with the disease phenotype in the four families studied, giving a lod score (logarithm of odds ratio) for linkage of 4.5, and subsequent linkage disequilibrium analysis conditional on linkage gave an additional lod score of 7.1.

Relationship between physical activity and physical performance in later life in different birth weight groups.

There is strong evidence that physical activity (PA) has an influence on physical performance in later life. Also, a small body size at birth has been associated with lower physical functioning in older age and both small and high birth weight have shown to be associated with lower leisure time physical activity. However, it is unknown whether size at birth modulates the association between PA and physical performance in old age. We examined 695 individuals from the Helsinki Birth Cohort Study born in Helsinki, Finland between 1934 and 1944. At a mean age of 70.7 years PA was objectively assessed with a multisensory activity monitor and physical performance with the Senior Fitness Test (SFT). Information on birth weight and gestational age was retrieved from hospital birth records. The study participants were divided in three birth weight groups, that is <3000 g, 3000-3499 g and ⩾3500 g. The volume of PA was significantly associated with the physical performance in all birth weight groups. However, the effect size of the association was large and significant only in men with a birth weight <3000 g (ß 0.59; 95% confidence interval 0.37-0.81, P<0.001). Our study shows that the association between PA and physical performance is largest in men with low birth weight. Our results suggest that men with low birth weight might benefit most from engaging in PA in order to maintain a better physical performance.

Detection of low frequency external electronic identification devices using commercial panel readers.

The ability of a commercially available panel reader system to read International Standards Organization-compliant electronic identification devices under commercial dairy conditions was examined. Full duplex (FDX-B) and half-duplex (HDX) low frequency radio-frequency identification external ear tags were utilized. The study involved 498 Holstein cows in the final 6 wk of gestation. There were 516 total electronic identification devices (n = 334 HDX and n = 182 FDX-B). Eighteen FDX-B were replaced with HDX during the study due to repeated detection failure. There were 6,679 HDX and 3,401 FDX-B device detection attempts. There were 220 (2.2%) unsuccessful and 9,860 (97.8%) successful identification detection attempts. There were 9 unsuccessful detection attempts for HDX (6,670/6,679 = 99.9% successful detection attempts) and 211 unsuccessful detection attempts for FDX-B (3,190/3,401 = 93.8% successful detection attempts). These results demonstrate that this panel system can achieve high detection rates of HDX devices and meet the needs of the most demanding management applications. The FDX-B detection rate was not sufficient for the most demanding applications, requiring a high degree of detection by panel readers. The lower FDX-B rate may not be inherent in the device technology itself, but could be due to other factors, including the particular panel reader utilized or the tuning of the panel reader.

Specific hybridization probes for mouse alpha 2(IX) and alpha 1(X) collagen mRNAs.

We have used polymerase chain reaction (PCR) technology and available cross-species sequence information to construct cDNA probes for mouse alpha 2(IX) and alpha 1(X) collagen transcripts. Sequencing confirmed the identification of the clones. Northern analysis proved sufficient divergence of the cloned sequences from other collagen transcripts: specific detection of the mouse 2.9 kb alpha 2(IX) and 3.3 kb alpha 1(X) collagen mRNAs was seen under normal hybridization and washing conditions.

Stable expression of recombinant human alpha 2-adrenoceptor subtypes in two mammalian cell lines: characterization with [3H]rauwolscine binding, inhibition of adenylate cyclase and RNase protection assay.

Cloning of the genes encoding distinct subtypes of human alpha 2-adrenergic receptors (alpha 2-AR) allows the separate recombinant expression of each individual subtype in heterologous systems. We report here the transfection, selection and preliminary pharmacological characterization of two mammalian cell lines, adherent Shionogi S115 mouse mammary tumour cells and human B-lymphoblastoid IBW4 cells growing in suspension, expressing the human alpha 2-AR subtypes alpha 2-C4 and alpha 2-C10 at densities of approx. 2 x 10(5) receptors/cell. Transfection of the subtype genes was verified using a specific RNase protection assay. Pharmacological characterization was carried out with [3H]rauwolscine binding, which was inhibited by oxymetazoline and prazosin in a subtype-selective manner. The sensitivity of (-)-noradrenaline binding to the GTP-analogue 5'-guanylylimidodiphosphate suggested that the receptors are coupled to G-proteins. This was verified in S115 cells by efficient inhibition of forskolin-stimulated cAMP production by the alpha 2-AR agonists, (-)-noradrenaline and clonidine. These cell lines thus appear to be suitable for pharmacological studies on receptor function and ligand binding.

Human COL9A1 and COL9A2 genes. Two genes of 90 and 15 kb code for similar polypeptides of the same collagen molecule.

Here we report the complete structure for the human COL9A1 and the complete sequence for the human COL9A2 genes. The COL9A1 gene is about 90 kb and consists of 38 exons. The COL9A2 gene is only about 15 kb, and it contains 32 exons. Sequence analysis of the promoter regions for the human COL9A2, the mouse Col9a2 and the human COL2A1 genes identified a conserved 14 bp sequence. The data also indicated that the alternative exon 1* found in intron 6 of the COL9A1 gene is separated from exon 7 only by a short intron in the chick, human, mouse and rat genes probably explaining why transcripts from exon 1* are spliced directly to exon 8.

Molecular cloning of the human alpha 2(IX) collagen cDNA and assignment of the human COL9A2 gene to chromosome 1.

Type IX collagen, a heterotrimer of alpha 1(IX), alpha 2(IX) and alpha 3(IX) chains, is a cartilage-specific fibril-associated collagen. In the process of characterizing genomic clones for the mouse alpha 2(IX) collagen gene four pairs of oligonucleotide primers designed for amplification of murine exon sequences were also utilized to construct cDNA clones for human alpha 2(IX) collagen spanning > 90% of the coding region. The amino acid and nucleotide sequence identities between human and chick are 78% and 71%, respectively. Localization of the COL9A2 gene to human chromosome 1 was subsequently performed using a panel of DNAs from human/rodent somatic cell hybrids.

Expression of type VI, IX and XI collagen genes and alternative splicing of type II collagen transcripts in fracture callus tissue in mice.

The levels of six mRNAs coding for constituent alpha-chains of three minor collagens of cartilage were analyzed in an experimental fracture model in normal and transgenic Del1 mice harboring a deletion mutation of exon 7 in the type II collagen gene. Reduced and retarded chondrogenesis in Del1 mice was evident in callus samples as reduced mRNA levels for the cartilage specific type IX and XI collagens at days 7 and 9 of fracture healing. Analysis of the calluses for alternative splicing of pro alpha 1(II) collagen mRNA also suggested retarded chondrogenesis in Del1 calluses. Another developmentally regulated step in limb development, a switch between alternative promoters of the alpha 1(IX) collagen gene, was also seen during fracture healing but was less obvious in Del1 calluses. Finally, the current data suggest that the abnormality in bone remodelling in Del1 mice involves activation of the genes coding for alpha 1(XI) and alpha 2(VI) collagens.

Differential expression of two alpha 2-adrenergic receptor subtype mRNAs in human tissues.

Genetic subtypes of alpha 2-adrenergic receptors (AR) may mediate distinct physiological functions, and undergo differential cell type-specific regulation. Thus, these distinct receptor subtypes are possible targets for the development of subtype-selective drugs. We have analyzed the tissue distribution of two human alpha 2-adrenoceptor subtype gene mRNAs, alpha 2-C4 and alpha 2-C10, in normal human fetal and adult tissues. Both receptor subtype mRNAs were abundantly expressed in fetal brain and choroid plexus. In non-neural fetal tissues, alpha 2-C10 mRNA was detected in spleen, kidney, adrenal gland, and skin, while alpha 2-C4 transcripts were observed only in kidney and skin. Most regions of the adult brain also expressed both subtypes, but with marked quantitative differences. For example, cerebral cortex contained predominantly alpha 2-C10 mRNA, whereas the caudate nucleus expressed mostly alpha 2-C4 mRNA. In adult peripheral tissues, alpha 2-C10 mRNA expression was most abundant in spleen and renal cortex, and expression of alpha 2-C4 mRNA was strongest in renal cortex and medulla. These different expression patterns provide evidence for the differential regulation of the two alpha 2-adrenergic receptor genes and warrant further investigation with techniques capable of improved anatomical resolution. Regional differences in receptor subtype expression may be valuable for the development of new, subtype-selective pharmacological agents with more targeted actions compared to currently used alpha 2-adrenoceptor agonists and antagonists.

What do women want? Women's experiences of infertility treatment.

Finnish women's experiences of infertility treatment were investigated by examining their satisfaction and dissatisfaction, and their most positive and negative experiences with the treatment. Three hundred and forty four (16%) out of the 2,189 women respondents to a 1994 postal survey (response rate 74%) had experienced difficulties in having a baby. Two-thirds had sought medical help, generally from private gynaecologists. Less than half of the women were satisfied with the infertility treatment, expressing less satisfaction than is generally found among health care clients. Dissatisfied women were more often 35-39 years of age, in treatment during the study period, in treatment in public clinics and not successful in having a baby. However, about one-third of the women were unsure about or did not give their opinion in regard to satisfaction. The subsequent birth of a baby was the most common reason for satisfaction. The most positive treatment experience was respectful, empathic and personal care from the doctor. Unsatisfactory encounters with health care personnel were the main reasons for dissatisfaction and were most often cited as the most negative treatment experience. This dissatisfaction could reflect relatively young and healthy women's assertive attitudes toward infertility care services in the context of the intimacy and vulnerability of childlessness.

Morbidity of very young infants with and without acute otitis media.

Perinatal and other morbidity of 96 consecutive infants with acute otitis media (AOM) before the age of 3 months is compared with that of 96 birthday- and sex-matched controls without AOM. Perinatal problems were found in 57 AOM infants and in 38 controls, prematurity and asphyxia being significantly (p less than 0.05) more common in the study group than in the controls. At the time of AOM, 51 infants had concurrent illnesses ('colds' excluded) or anomalies, while only 19 controls (p less than 0.001) showed any respective morbidity during their 3 months of life. While AOM infants frequently presented with other, especially respiratory, infections, the controls hardly ever did so. Symptomatology during otitis was varying, and frequently suggestive of respiratory problems other than AOM. Subsequent otitis morbidity of AOM infants was heavy, but other disease history was similar to that of the controls. The study stresses the importance of examining the ears in young infants presenting with any illness, and especially of a respiratory nature.

Mequitazine and dexchlorpheniramine in perennial rhinitis. A double-blind cross-over placebo-controlled study.

The therapeutic effect and adverse reactions of two antihistamines, mequitazine and dexchlorpheniramine were double-blindly compared both to placebo, to each other and to the pre-treatment status in 29 adult patients suffering from perennial rhinitis. Dexchlorpheniramine relieved the rhinitis symptoms significantly (p less than 0.01) better compared to placebo while mequitazine did not differ from placebo. 20 out of 29 patients chose dexchlorpheniramine as their favourite drug. Dexchlorpheniramine reduced all the separate symptoms studied (obstruction, rhinorrhoea, sneezing) significantly, mequitazine relieving merely rhinorrhoea. In anterior rhinoscopy mucosal congestion was reduced both by dexhlorpheniramine (p less than 0.01) and by mequitazine (p less than 0.05) but secretion or lividity showed no difference between the active drugs and placebo. The occurrence of side-effects was not significantly different between the drugs. In controlling perennial rhinitis symptoms mequitazine was markedly inferior to dexchlorpheniramine and only slightly better than placebo.