The value of virus serology in epidemiological studies of acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a major health problem in young children. There is a general conception that AOM is a bacterial disease but with the availability of sensitive diagnostic methods, it has gradually become evident that viruses play an important role in the pathogenesis of AOM. Paired blood samples are seldom taken from infants although valuable information could be obtained by serological methods. During the recent Finnish Otitis Media (FinOM) Cohort Study, in addition to nasopharyngeal aspirates (NPA) and middle ear fluids (MEF), paired acute and convalescent serum samples were collected from children with AOM. OBJECTIVES: To establish the diagnostic value of serological methods in etiological and epidemiological studies of AOM. STUDY DESIGN: A complete set of NPA, MEF, and paired sera was collected during 447 events of AOM experienced by 179 children between 2 months and 2 years of age. Antigens of respiratory syncytial virus (RSV), adenoviruses, influenza A and B, and parainfluenza types 1-3 in NPAs and MEFs were detected by time-resolved fluoroimmunoassay (TR-FIA), and antibody titers were determined by complement fixation test (CFT) or by enzyme immunoassay. RESULTS: A total of 163 virus-positive events were identified. Of those, only 34 were positive by TR-FIA and by serology. From 48 events a positive result was obtained only by TR-FIA and from 81 only by serology. CONCLUSION: Although serological methods are usually of little use in clinical practice, epidemiological studies clearly gain value if serology is included. The number of virus-positive findings dramatically increased by including serological tests in the diagnostic work-up of these AOM events.     

Haplotype structure,LD blocks,and uneven recombination within the LRP5 gene

Patterns of linkage disequilibrium (LD) in the human genome are beginning to be characterized, with a paucity of haplotype diversity in "LD blocks," interspersed by apparent "hot spots" of recombination. Previously, we cloned and physically characterized the low-density lipoprotein-receptor-related protein 5 (LRP5) gene. Here, we have extensively analysed both LRP5 and its flanking three genes, spanning 269 kb, for single nucleotide polymorphisms (SNPs), and we present a comprehensive SNP map comprising 95 polymorphisms. Analysis revealed high levels of recombination across LRP5, including a hot-spot region from intron 1 to intron 7 of LRP5, where there are 109 recombinants/Mb (4882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. This region of high recombination could be delineated into three to four hot spots, one within a 601-bp interval. For LRP5, three haplotype blocks were identified, flanked by the hot spots. Each LD block comprised over 80% common haplotypes, concurring with a previous study of 14 genes that showed that common haplotypes account for at least 80% of all haplotypes. The identification of hot spots in between these LD blocks provides additional evidence that LD blocks are separated by areas of higher recombination.     

Expression of human pim family genes is selectively up-regulated by cytokines promoting T helper type 1, but not T helper type 2, cell differentiation

Cytokines are the most important inducers of T helper (Th) cell differentiation. Interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) are responsible for human Th1-cell differentiation, while IL-4 is the critical cytokine promoting Th2-cell development. These two subsets of cells co-ordinate immunological responses to pathogens as well as autoimmune or allergic reactions. The pim family of proto-oncogenes encodes serine/threonine-specific kinases involved in cytokine-mediated signalling pathways in haematopoietic cells. Here we demonstrate that expression of pim-1 and pim-2 mRNAs is selectively up- or down-regulated in human cord-blood-derived CD4+ cells freshly induced to polarize towards Th1 or Th2 cells, respectively, whereas their expression is inhibited in both cell types by the immunosuppressive transforming growth factor beta (TGF-beta). Moreover, the Th1-specific cytokines IL-12 and IFN-alpha, but not the Th2-specific cytokine IL-4, transiently up-regulate pim-1 and pim-2 mRNA expression in human peripheral blood T cells and natural killer cells. In addition, the Pim-1 protein levels are strongly up-regulated by Th1-specific cytokines in all of these cell types. Taken together, our results suggest that pim genes and their protein products are involved in the early differentiation process of T helper cells.     

Platelet responses and coagulation activation on polylactide and heparin-polycaprolactone-L-lactide-coated polylactide stent struts

Despite modern stent technology and effective antiplatelet therapy, metallic stents carry the risk of (sub)acute thrombosis. Our aim was to examine short-term differences in platelet deposition and coagulation activation between biodegradable polylactide (PLA), heparin-polycaprolactone-L-lactide-coated polylactide (hepa-P(CL95/L-LA5)-PLA), and stainless steel (SS) stent struts. Gel-filtered platelets (GFP) and platelet-rich plasma (PRP) were labeled with 10 nM (3)H-serotonin. Platelet deposition was measured after incubation of the stent struts in human serum albumin-coated wells at 37 degrees C in either GFP or PRP. Platelet morphology was studied by scanning electron microscopy (SEM). For coagulation activation, the stent struts were incubated in either PRP or platelet-poor plasma (PPP), anticoagulated with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), followed by measurement of fibrinogen, thrombin time (TT), prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex (TAT). SS showed adherence of larger amounts of GFPs than did PLA at a platelet density of 300 x 10(6)/mL (p < 0.05). Furthermore, representative SEM studies showed more platelet spreading on SS than on PLA stent struts. Between PLA and SS, coagulation activity did not differ at any assessment. Based on prolonged TT values in plasma, the heparin coating strongly inhibited coagulation (p < 0.05). The values of soluble TAT and F1+2 for PLA were similar to those of controls, i.e., to incubated suspensions without a stent strut. In conclusion, when compared with stainless steel, both PLA and hepa-P(CL95/L-LA5)-PLA appear hemocompatible as intravascular stent materials.     

The hydrolethalus syndrome: delineation of a "new", lethal malformation syndrome based on 28 patients

We describe a lethal malformation syndrome in 28 newborn infants from 18 families. The main manifestations were hydrocephalus (often with an unusual structure of the brain and the occipital bone), very small mandible, Polydactyly, congenital heart defect, abnormalities of the respiratory organs, and (different from the Meckel syndrome) normal kidneys. Polyhydramnios and stillbirth or neonatal death were the rule. Autosomal recessive inheritance is evident. This syndrome is another in the group of rare recessive disorders which are found in Finland. Because of the 25 % recurrence risk and possibilities for prenatal diagnosis, this syndrome should be recognized by paediatricians and, because of the frequent stillbirths, also by obstetricians and pathologists. The name hydrolethalus syndrome (hydramnios, hydrocephalus, lethality) may be of help in this.     

Three hands: fragmentation of human bodily awareness

We describe patient E.P. who occasionally perceives a ‘ghost' hand which copies the previous positions of the left hand with a 0.5–1 min time lag, but follows the movement patterns of the right hand. The symptoms started after an operation of a ruptured aneurysm, followed by an infarction of the right frontal lobe; E.P. also has a previously lesioned corpus callosum. Neuromagnetic recordings revealed that activity of the left secondary somatosensory cortex was strongly suppressed during the ghost arm percept, thereby providing an objective correlate for E.P.'s sensations. We conclude that simultaneous mental contents about body scheme may be based on neural information extracted at considerably different times, resulting in fragmentation of bodily awareness.     

Heritability and risk factors of uterine fibroids--the Finnish Twin Cohort study

OBJECTIVES: Our aim was to study heritability, risk factors and hospitalization for uterine fibroids. METHODS: A random sample of 80 MZ and 80 DZ twins from the Finnish Twin Cohort were invited and 51% of the eligible women (n=82, 17 MZ and 16 DZ pairs, 40-47 years, mean age 43.0), underwent a transvaginal ultrasound. The entire cohort of 13872 women was linked to the national hospital discharge registry 1972-1990. RESULTS: Prevalence of fibroids was 66% and the average number of fibroids 1.7. The casewise concordance for being hospitalized for uterine fibroids was higher in MZ (0.31, 95% CI 0.24-0.37) than in DZ pairs (0.18, 95% CI 0.14-0.22). The proportion of variance in liability to fibroid hospitalization accounted for by genetic factors was 54.8% (95% CI 46.2-62.7%). Women with fibroids had higher body mass index (23.7 vs 21.7, P=0.0086), lower age at first birth (25.7 vs 29.3, P=0.012) and higher parity (3+ children 48.2 vs 29.6%, P=0.009) than women without fibroids. Risk ratio (RR) for fibroids in a MZ twin whose sister had been diagnosed with fibroids was 1.1 (95% CI 0.08;15), for a DZ twin 1.1 (95% CI 0.16;8.8) and for all twins 1.3 (95% CI 0.3; 6.1). Intraclass correlation for the number of fibroids was 0.24 for MZ and 0.11 for DZ twins, yielding an heritability estimate of 0.26. CONCLUSION: Reproductive and anthropometric factors may have at least as large role in pathogenesis of fibroids than genetic factors.     

Effects of ospemifene, a novel SERM, on vascular markers and function in healthy, postmenopausal women

OBJECTIVE: Ospemifene, a novel selective estrogen receptor modulator (SERM), shows promise for bone preservation in postmenopausal women. This study examined the effects of ospemifene on different vascular surrogate markers. DESIGN: A double-blinded study was conducted in 160 healthy, postmenopausal women who used, in a randomized order, ospemifene (at daily doses of 30, 60, or 90 mg) or placebo for 3 months. RESULTS: Although ospemifene caused falls from basal levels in total cholesterol, low-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, and a rise in high-density lipoprotein cholesterol, the only statistically significant difference between ospemifene and placebo was an increase of triglyceride levels (11.3%) in the 90-mg group. Ospemifene caused no significant effect on endothelial markers or homocysteine. Of the markers reflecting coagulation and fibrinolysis, plasma fibrinogen was significantly reduced in the 60- and 90-mg groups of ospemifene (8.7% and 8.5%, respectively) when compared with the placebo group. No changes were seen in generation of thrombin or degradation of crosslinked fibrin D-dimer. The uterine or carotid arteries and 24-h ambulatory blood pressure were not affected by ospemifene. Ospemifene caused no changes in basal insulin or in a 2-h glucose tolerance test, suggesting unaltered insulin sensitivity. CONCLUSIONS: Neutral effects of short-term use of ospemifene on vascular surrogate markers imply no effect for ospemifene on the risk for cardiovascular disorders in healthy, postmenopausal women.     

Maternal Vitamin C and Iron Intake during Pregnancy and the Risk of Islet Autoimmunity and Type 1 Diabetes in Children: A Birth Cohort Study

Our aim was to study the associations between maternal vitamin C and iron intake during pregnancy and the offspring’s risk of developing islet autoimmunity and type 1 diabetes. The study was a part of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort including children genetically at risk of type 1 diabetes born between 1997–2004. The diets of 4879 mothers in late pregnancy were assessed with a validated food frequency questionnaire. The outcomes were islet autoimmunity and type 1 diabetes. Cox proportional hazards regression analysis adjusted for energy, family history of diabetes, human leukocyte antigen (HLA) genotype and sex was used for statistical analyses. Total intake of vitamin C or iron from food and supplements was not associated with the risk of islet autoimmunity (vitamin C: HR 0.91: 95% CI (0.80, 1.03), iron: 0.98 (0.87, 1.10)) or type 1 diabetes (vitamin C: 1.01 (0.87, 1.17), iron: 0.92 (0.78, 1.08)), neither was the use of vitamin C or iron supplements associated with the outcomes. In conclusion, no association was found between maternal vitamin C or iron intake during pregnancy and the risk of islet autoimmunity or type 1 diabetes in the offspring.