Risk factors for parvovirus B19 infection in pregnancy

Context  Parvovirus B19 infection during pregnancy has been associated with fetal death. However, the incidence of and risk factors for infection in pregnant women have not been well studied. Objectives  To estimate a pregnant woman's risk of infection with parvovirus B19 in epidemic and endemic situations and to study risk factors for infection. Design  Population-based cohort study conducted between November 1992 and June 1994. Setting  Three regions in Denmark. Participants  A total of 30,946 pregnant women from a consecutive and population-based screening. Main Outcome Measures  Specific IgG antibodies in serum samples obtained in the first trimester of pregnancy and from the newborn infant to assess past infection and seroconversion. Information on family structure, educational background, socioeconomic status, and pregnancy outcome was obtained from national registers. Results  Based on 30,946 serum samples, 65.0% of pregnant women had evidence of past infection. Annual seroconversion rates among susceptible women during endemic and epidemic periods were 1.5% (95% confidence interval [CI], 0.2%-1.9%) and 13.0% (95% CI, 8.7%-23.1%), respectively. Baseline seropositivity was significantly correlated with increasing number of siblings, having a sibling of the same age, number of own children, and occupational exposure to children. Risk of acute infection increased with the number of children in the household as follows: 0 children odds ratio (OR), 1 (reference); 1 child OR, 3.17 (95% CI, 2.24-4.49); 2 children OR, 5.47 (95% CI, 3.55-8.45); 3 or more children OR, 7.54 (95% CI, 3.80-14.94). Having children aged 6 to 7 years resulted in the highest rate of seroconversion among mothers (6.8%; OR, 4.07; 95% CI, 1.89-8.73). Compared with other pregnant women, nursery school teachers had a 3-fold increased risk of acute infection (OR, 3.09; 95% CI, 1.62-5.89). Population-attributable risk of seroconversion was 55.4% for number of own children and 6.0% for occupational exposure. Conclusions  The risk of infection is high for susceptible pregnant women during epidemics and associated with the level of contact with children. Nursery school teachers have the highest occupational risk, but most infections seem to be the result of exposure to the woman's own children.      

Ultrastructure of human cumulus-oocyte complexes from healthy and atretic follicles

Follicular fluids with cumulus-oocyte complexes and granulosa cells were aspirated from antral follicles in healthy women at different stages of the normal menstrual cycle. The cumulus-oocyte complexes were processed for light and electron microscopy and classified as pre-ovulatory, healthy non-pre-ovulatory and atretic by certain light microscopical criteria, i.e. degree of expansion, number of layers and pycnotic nuclei in the cumulus investment, size of the peri-vitelline space and oocyte nuclear morphology. Their follicles were similarly classified by follicular steroid measurements and/or flow cytometric DNA analyses of the aspirated granulosa cells. A high degree of correlation between these classifications was found. Moreover, pre-ovulatory and atretic cumulus-oocyte complexes showed particular fine morphological characteristics, some of which were different while others appeared to be identical. Similarities were increased number of lipid droplets in the cumulus cells, widened peri-vitelline space, peripheral displacement or breakdown of the oocyte nucleus and disconnection of the junctions between cumulus cell projections and the oolemma. In addition to the criteria used for the light microscopical classification, pre-ovulatory complexes were characterized by release of the content of cortical granules while atretic ones displayed cumulus cells with pseudopodia-like projections, cumulus cells in the perivitelline space and lipid droplets in the ooplasm.     

A critical appraisal of the use of umbilical artery Doppler ultrasound in high-risk pregnancies: use of meta-analyses in evidence-based obstetrics.

OBJECTIVES: To reanalyze randomized controlled trials on the use of umbilical artery Doppler velocimetry in high-risk pregnancies and determine which high-risk pregnancies benefit from the use of Doppler velocimetry. METHODS: Searching Medline, the Cochrane Library and Embase we found 13 randomized controlled trials on the use of Doppler velocimetry in high-risk pregnancies. Of these, six included pregnancies with strictly defined suspected intrauterine growth restriction and/or hypertensive disease of pregnancy ('well-defined studies'); the rest included a great variety of high-risk pregnancies ('general risk studies'). The studies were analyzed with particular regard to the heterogeneity and to outcome. Audits of the perinatal deaths reported in the randomized controlled trials were performed by a panel of 32 international experts. RESULTS: The 'well-defined studies' had a more uniform study design as compared to the 'general risk studies' and they showed a significant reduction in antenatal admissions (odds ratio, 0.56; 95% confidence interval, 0.43-0.72), inductions of labor (0.78; 0.63-0.96), elective deliveries (inductions of labor and elective Cesarean sections) (0.73; 0.61-0.88) and Cesarean sections (0.78; 0.65-0.94). By perinatal audit it was found that more perinatal deaths in the 'well-defined studies' were potentially avoidable by use of Doppler velocimetry ( P < 0.0005) and the rate of avoidable perinatal deaths was higher among controls (50%) than cases (20%) in this group. CONCLUSION: The randomized controlled trials on umbilical artery Doppler velocimetry show major differences regarding study design and technical and clinical issues and, therefore, they should not be pooled in a simple meta-analysis. By stratification it was found that only in pregnancies with suspected intrauterine growth restriction and/or hypertensive disease of pregnancy will the use of umbilical artery Doppler velocimetry reduce the number of perinatal deaths and unnecessary obstetric interventions.     

CSF 5-HIAA and aggression in female macaque monkeys: species and interindividual differences

Rationale: While the relationship among CSF 5-HIAA, impulsivity, and aggression is well characterized in males, its investigation in females is limited, and no studies have assessed its generalizability across primates by making simultaneous comparisons between and within closely-related species. Objectives: We tested three hypotheses. First, that female rhesus macaques would have lower CSF 5-HIAA concentrations and be more aggressive than would female pigtailed macaques. Second, that females of both macaque species would exhibit an inverse relationship between interindividual differences in CSF 5-HIAA concentrations and rates of severe aggression. Third, that subjects with high CSF 5-HIAA concentrations would be higher in social dominance within their respective groups than would subjects with low CSF 5-HIAA concentrations. Methods: We obtained CSF samples from 61 individually housed female primates of two closely related species: rhesus macaques (Macaca mulatta) and pigtailed macaques (Macaca nemestrina). We later placed subjects in unisex social groups, and correlated interindividual differences in CSF 5-HIAA with aggression, wounding, and acquisition of social dominance rank. Results: Between-species analyses indicated higher CSF 5-HIAA concentrations in pigtailed macaques, and higher rates of high-intensity aggression, escalated aggression, and wounds requiring medical treatment in rhesus macaques. Within-species analyses indicated that interindividual differences in CSF 5-HIAA concentrations were inversely correlated with escalated aggression and positively correlated with social dominance rank. Conclusions: These findings show that agonistic and social differences between closely-related species are correlated with CNS serotonin activity, as species that show relatively high rates of severe aggression also tend to have low concentrations of CSF 5-HIAA. We conclude that serotonergic functioning plays an important role in controlling impulses that regulate severe aggression and social dominance relationships in both male and female primates, and that between-species differences in agonistic temperament can be predicted by species typical CNS serotonin functioning. Received: 30 December 1998 / Final version: 3 June 1999     

Left-handedness and longevity in primates.

In the present research we used the rhesus macaque to model the decline in the incidence of left-handedness that has been noted in the aged human population. We found a significant group-level bias towards use of the left hand among young-adult macaques, and a significant group-level bias towards use of the right hand among aged macaques. The distribution of hand preference across age classes cannot be explained through simple elimination of left-handed subjects in the aged population. Rather, our data are consistent with a maturational view positing increased use of the right hand with increased age. Similar findings across phylogenetically diverse primate taxa suggest that this phenomenon is an evolutionarily ancient trait. Greater use of the left hand in male versus female macaques indicates that sex differences in hand preference are also deeply rooted in our primate origins.     

Autoimmune diseases in patients with multiple sclerosis and their first-degree relatives: a nationwide cohort study in Denmark

BACKGROUND: Multiple sclerosis (MS) and other autoimmune diseases might cluster. Our aim was to estimate the relative risk (RR) of other autoimmune diseases among MS patients and their first-degree relatives in a population-based cohort study. METHODS: Using the Danish Multiple Sclerosis Register, the Danish Hospital Discharge Register, and the Danish Civil Registration System, we estimated RRs for 42 different autoimmune diseases in a population-based cohort of 12 403 MS patients and 20 798 of their first-degree relatives. Ratios of observed to expected numbers of autoimmune diseases, based on national sex-, age-, and period-specific incidence rates, served as measures of the RRs. RESULTS: Compared with the general population, MS patients were at an increased risk of developing ulcerative colitis (RR = 2.0 (95% confidence interval (CI): 1.4-2.8), n = 29) and pemphigoid (RR = 15.4 (CI: 8.7-27.1), n = 12) but at reduced risk of rheumatoid arthritis (RR = 0.5 (CI: 0.4-0.8), n = 28) and temporal arteritis (RR = 0.5 (CI: 0.3-0.97), n = 11). First-degree relatives of MS patients were at increased risks of Crohn's disease (RR = 1.4 (CI: 1.04-1.9), n = 44), ulcerative colitis (RR = 1.3 (CI: 0.99-1.7), n = 51), Addison's disease (RR = 3.4 (CI: 1.3-9.0), n = 4), and polyarteritis nodosa (RR = 3.7 (CI: 1.4-10.0), n = 4). CONCLUSION: PATIENTS: with MS and their first-degree relatives seem to be at an increased risk of acquiring certain other autoimmune diseases.     

Anti-Müllerian hormone remains highly expressed in human cumulus cells during the final stages of folliculogenesis

This study evaluated whether anti-Müllerian hormone (AMH) was differentially expressed in cumulus (CC) and granulosa (GC) cells from large antral and pre-ovulatory follicles collected from individual follicles in women undergoing in-vitro maturation (IVM) or IVF treatment. Expression studies of AMH, AMH receptor 2, FSH receptor, aromatase and androgen receptor were performed in CC in IVM patients where cumulus-oocyte-complex had expanded, CC in IVM patients where cumulus-oocyte-complex remained compacted, GC from immature follicles and CC and GC from IVF patients. Microarray data on corresponding GC and CC from follicles from IVF patients was included. AMH expression was significantly higher in CC than in GC from both mature and immature follicles and in CC from immature follicles than in CC from pre-ovulatory follicles from IVF patients (P < 0.05). AMH expression was significantly higher in CC that remained compacted compared with those that had expanded (P < 0.008). AMH was correlated to the expression of FSH receptor, androgen receptor and AMH receptor 2 but not to aromatase expression. The expression pattern of AMH receptor 2 reflected that of AMH. AMH may exert intrafollicular functions even in human large antral and pre-ovulatory follicles and may be related to follicular health.     

Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal and lesional psoriatic skin

Abnormal epidermal proliferation and differentiation characterize the inflammatory skin disease psoriasis. Here we demonstrate that expression of PPARdelta mRNA and protein is markedly upregulated in psoriatic lesions and that lipoxygenase products accumulating in psoriatic lesions are potent activators of PPARdelta. The expression levels of NF-kappaB p50 and p65 were not significantly altered in lesional compared with nonlesional psoriatic skin. In the basal layer of normal epidermis both p50 and p65 were sequestered in the cytoplasm, whereas p50, but not p65, localized to nuclei in the suprabasal layers, and this distribution was maintained in lesional psoriatic skin. In normal human keratinocytes PPAR agonists neither impaired IL-1beta-induced translocation of p65 nor IL-1beta-induced NF-kappaB DNA binding. We show that PPARdelta physically interacts with the N-terminal Rel homology domain of p65. Irrespective of the presence of agonists none of the PPAR subtypes decreased p65-mediated transactivation in keratinocytes. In contrast p65, but not p50, was a potent repressor of PPAR-mediated transactivation. The p65-dependent repression of PPARdelta- but not PPARalpha- or PPARgamma-mediated transactivation was partially relieved by forced expression of the coactivators p300 or CBP. We suggest that deficient NF-kappaB activation in chronic psoriatic plaques permitting unabated PPARdelta-mediated transactivation contributes to the pathologic phenotype of psoriasis.