The influence of maternal psychological distress on the mode of birth and duration of labor: findings from the FinnBrain Birth Cohort Study.

Antepartum depression, general anxiety symptoms, and pregnancy-related anxiety have been recognized to affect pregnancy outcomes. Systematic reviews on these associations lack consistent findings, which is why further research is required. We examined the associations between psychological distress, mode of birth, epidural analgesia, and duration of labor. Data from 3619 women with singleton pregnancies, from the population-based FinnBrain Birth Cohort Study were analyzed. Maternal psychological distress was measured during pregnancy at 24 and 34 weeks, using the Pregnancy-Related Anxiety Questionnaire-Revised 2 (PRAQ-R2) and its subscale "Fear of Giving Birth" (FOC), the anxiety subscale of the Symptom Checklist-90 (SCL-90) and the Edinburgh Postnatal Depression Scale (EPDS). Mode of birth, epidural analgesia, and labor duration were obtained from the Finnish Medical Birth Register. Maternal psychological distress, when captured with PRAQ-R2, FOC, and SCL-90, increased the likelihood of women having an elective cesarean section (OR: 1.04, 95% CI 1.01-1.06, p = .003; OR: 1.13, 95% CI 1.07-1.20, p < .001; OR: 1.06, 95% CI 1.03-1.10, p = .001), but no association was detected for instrumental delivery or emergency cesarean section. A rise in both the PRAQ-R2, and FOC measurements increased the likelihood of an epidural analgesia (OR: 1.02, 95% CI 1.01-1.03, p = .003; OR: 1.09, 95% CI 1.05-1.12, p < .001) and predicted longer second stage of labor (OR: 1.01, 95% CI 1.00-1.01, p = .023; OR: 1.03, 95% CI 1.02-1.05, p < .001). EPDS did not predict any of the analyzed outcomes. The results indicate that maternal anxiety symptoms (measured using PRAQ-R2, FOC, and SCL-90) are associated with elective cesarean section. Psychological distress increases the use of epidural analgesia, but is not associated with complicated vaginal birth.

Molecular Evidence of Chlamydia-Like Organisms in the Feces of Myotis daubentonii Bats.

Chlamydia-like organisms (CLOs) are recently identified members of the Chlamydiales order. CLOs share intracellular lifestyles and biphasic developmental cycles, and they have been detected in environmental samples as well as in various hosts such as amoebae and arthropods. In this study, we screened bat feces for the presence of CLOs by molecular analysis. Using pan-Chlamydiales PCR targeting the 16S rRNA gene, Chlamydiales DNA was detected in 54% of the specimens. PCR amplification, sequencing, and phylogenetic analysis of the 16S rRNA and 23S rRNA genes were used to classify positive specimens and infer their phylogenetic relationships. Most sequences matched best with Rhabdochlamydia species or uncultured Chlamydia sequences identified in ticks. Another set of sequences matched best with sequences of the Chlamydia genus or uncultured Chlamydiales from snakes. To gain evidence of whether CLOs in bat feces are merely diet borne, we analyzed insects trapped from the same location where the bats foraged. Interestingly, the CLO sequences resembling Rhabdochlamydia spp. were detected in insect material as well, but the other set of CLO sequences was not, suggesting that this set might not originate from prey. Thus, bats represent another potential host for Chlamydiales and could harbor novel, previously unidentified members of this order. IMPORTANCE: Several pathogenic viruses are known to colonize bats, and recent analyses indicate that bats are also reservoir hosts for bacterial genera. Chlamydia-like organisms (CLOs) have been detected in several animal species. CLOs have high 16S rRNA sequence similarity to Chlamydiaceae and exhibit similar intracellular lifestyles and biphasic developmental cycles. Our study describes the frequent occurrence of CLO DNA in bat feces, suggesting an expanding host species spectrum for the Chlamydiales As bats can acquire various infectious agents through their diet, prey insects were also studied. We identified CLO sequences in bats that matched best with sequences in prey insects but also CLO sequences not detected in prey insects. This suggests that a portion of CLO DNA present in bat feces is not prey borne. Furthermore, some sequences from bat droppings not originating from their diet might well represent novel, previously unidentified members of the Chlamydiales order.

Antibody to Chlamydia trachomatis proteins, TroA and HtrA, as a biomarker for Chlamydia trachomatis infection.

We studied whether antibody to two chlamydial proteins (TroA and HtrA) could be used as biomarkers of Chlamydia trachomatis infection. METHODS: Recombinant proteins C. trachomatis TroA and HtrA were used as antigens in enzyme immunoassay (EIA). Both IgG and IgA antibody responses were studied. RESULTS: IgG or IgA antibody to either protein was infrequently detected in sera from healthy blood donors or virgin girls. Patients attending the STI Clinic and patients with perihepatitis had often IgG antibody against TroA (25 and 50 % respectively) and HtrA (21 and 38 % respectively). Especially in sera from patients with chlamydial perihepatitis, the A450nm values with TroA were high (mean 1.591). A positive correlation between C. trachomatis MIF antibody and TroA (r  = 0.7) as well as HtrA (r  = 0.5) antibody was observed in sera from STI clinic patients and perihepatitis patients. Individuals with C. trachomatis infection and positive serology already when seeking medical attention had higher A450nm values for TroA (0.638) and HtrA (0.836) than patients with no marker of previous exposure or with no infection (0.208 and 0.234 respectively). Diagnosis of genital C. trachomatis infection is often NAAT-based, whereas serology has little value in testing for uncomplicated genital C. trachomatis infection. TroA and HtrA antibodies are potential biomarkers for evaluation of ascending and repeated C. trachomatis infection.

MetIDB: a publicly accessible database of predicted and experimental 1H NMR spectra of flavonoids.

Identification of natural compounds, especially secondary metabolites, has been hampered by the lack of easy to use and accessible reference databases. Nuclear magnetic resonance (NMR) spectroscopy is the most selective technique for identification of unknown metabolites. High quality (1)H NMR (proton nuclear magnetic resonance) spectra combined with elemental composition obtained from mass spectrometry (MS) are essential for the identification process. Here, we present MetIDB, a reference database of experimental and predicted (1)H NMR spectra of 6000 flavonoids. By incorporating the stereochemistry, intramolecular interactions, and solvent effects into the prediction model, chemical shifts and couplings were predicted with great accuracy. A user-friendly web-based interface for MetIDB has been established providing various interfaces to the data and data-mining possibilities. For each compound, additional information is available comprising compound annotation, a (1)H NMR spectrum, 2D and 3D structure with correct stereochemistry, and monoisotopic mass as well as links to other web resources. The combination of chemical formula and (1)H NMR chemical shifts proved to be very efficient in metabolite identification, especially for isobaric compounds. Using this database, the process of flavonoid identification can then be significantly shortened by avoiding repetitive elucidation of already described compounds.

Performance of multicomponent self-organizing regression (MCSOR) in QSAR, QSPR, and multivariate calibration: comparison with partial least-squares (PLS) and validation with large external data sets.

A novel method for underdetermined regression problems, multicomponent self-organizing regression (MCSOR), has been recently introduced. Here, its performance is compared with partial least-squares (PLS), which is perhaps the most widely adopted multivariate method in chemometrics. A potpourri of models is presented, and MCSOR appears to provide highly predictive models that are comparable with or better than the corresponding PLS models in large internal (leave-one-out, LOO) and pseudo-external (leave-many-out, LMO) validation tests. The "blind" external predictive ability of MCSOR and PLS is demonstrated employing large melting point, factor Xa, log P and log S data sets. In a nutshell, MCSOR is fast, conceptually simple (employing multiple linear regression, MLR, as a statistical tool), and applicable to all kinds of multivariate problems with single Y-variable.

Dynamics of diabetes-associated autoantibodies in young children with human leukocyte antigen-conferred risk of type 1 diabetes recruited from the general population.

This study characterized the dynamics of islet cell antibodies (ICA), insulin antibodies (IAA), glutamic acid decarboxylase antibodies (GADA), and IA-2 antibodies (IA-2A) in 1006 children recruited from the general population due to human leukocyte antigen (HLA) DQB1-conferred risk for type 1 diabetes (T1D). By the age of 5 yr, 13.8% of the children had had one or more autoantibodies in at least one sample drawn at 3- to 12-month intervals from birth, whereas 6.1% had had one or more of the three autoantibodies to biochemically defined antigens in at least two consecutive samples. The cumulative frequencies of positivity for at least two antibodies ranged from 3.2-4.4%. Seventy-five children (7.5%) had at least once ICA, 83 (8.3%) had IAA, 46 (4.6%) had GADA, and 33 (3.3%) had IA-2A. IAA were transient more frequently than the other antibodies (P < or = 0.03) and fluctuated between positivity and negativity more often than ICA (P = 0.001). The genetically high risk children were positive for each autoantibody reactivity more often (P < or = 0.03) than the moderate risk subjects. Thirteen of the 1006 children (1.3%) presented with T1D by the age of 5 yr. The most sensitive predictors of T1D were ICA and IAA, whereas the most specific predictor was IA-2A. Positivity for at least two autoantibodies of IAA, GADA, and IA-2A had the highest positive predictive value for T1D (34%). We conclude that the frequency of various diabetes-associated autoantibodies increases at a relatively stable rate at least up to the age of 5 yr. Persistent positivity for two or more autoantibodies appears to reflect destructive progressive beta-cell autoimmunity, whereas positivity for a single autoantibody may represent harmless nonprogressive or even regressive beta-cell autoimmunity.

Improving the performance of SOMFA by use of standard multivariate methods.

Self-Organizing Molecular Field Analysis (SOMFA) comes with a built-in regression methodology, the Self-Organizing Regression (SOR), instead of relying on external methods such as PLS. In this article we present a proof of the equivalence between SOR and SIMPLS with one principal component. Thus, the modest performance of SOMFA on complex datasets can be primarily attributed to the low performance of the SOMFA regression methodology. A multi-component extension of the original SOR methodology (MCSOR) is introduced, and the performances of SOR, MCSOR and SIMPLS are compared using several datasets. The results indicate that in general the performance of SOMFA models is greatly improved if SOR is replaced with a more sophisticated regression method. The results obtained for the Cramer (CBG) dataset further underline the fact that it is a very poor benchmark dataset and should not be used to evaluate the performance of QSAR techniques.

Glasgow Aneurysm Score as a predictor of immediate outcome after surgery for ruptured abdominal aortic aneurysm.

BACKGROUND: The aim of the study was to assess the value of the Glasgow Aneurysm Score in predicting postoperative death after repair of a ruptured abdominal aortic aneurysm (AAA). METHODS: Between 1991 and 1999, 836 patients underwent surgery for ruptured AAA. Their operative risk at presentation was evaluated retrospectively using the Glasgow Aneurysm Score, based on data from the nationwide Finnvasc registry. RESULTS: The operative mortality rate was 47.2 per cent (395 of 836); 164 patients (19.6 per cent) had cardiac complications and 164 (19.6 per cent) required intensive care treatment for more than 5 days. Predictors of postoperative death in univariate analysis were: coronary artery disease (P = 0.005), preoperative shock (P < 0.001), age (P < 0.001), and the Glasgow Aneurysm Score (P < 0.001). In multivariate analysis the predictors were: preoperative shock (odds ratio (OR) 2.13 (95 per cent confidence interval (c.i.) 1.45 to 3.11); P < 0.001) and the Glasgow Aneurysm Score (for an increase of ten units: OR 1.81 (95 per cent c.i. 1.54 to 2.12); P < 0.001). Receiver-operator characteristic (ROC) curves showed that the best cut-off value of the Glasgow Aneurysm Score in predicting postoperative death was 84 (area under the curve 0.75 (95 per cent c.i. 0.72 to 0.78), standard error 0.17; P < 0.001). The operative mortality rate was 28.2 per cent (114 of 404) in patients with a Glasgow Aneurysm Score of 84 or less, compared with 65.0 per cent (281 of 432) in those with a score greater than 84 (P < 0.001). CONCLUSION: The Glasgow Aneurysm Score predicted postoperative death after repair of ruptured AAA in this series.

Humoral beta-cell autoimmunity is rare in patients with the congenital rubella syndrome.

The congenital rubella syndrome (CRS) is associated with increased risk for diabetes and thyroid disease. However, the mechanisms by which the rubella virus may cause these diseases are poorly characterized. Previous studies were carried out before modern immunological methods were available. The present study aimed at evaluating whether autoimmune mechanisms are involved in the pathogenesis by analysing antibodies to biochemically characterized autoantigens. The incidence of clinical diabetes, thyroid disease, coeliac disease and related antibodies (islet cell antibodies, ICA; insulin autoantibodies, IAA; antibodies to the tyrosine phosphatase related IA-2 molecule, IA-2 A and glutamic acid decarboxylase, GADA; thyroid peroxidase, TPO; tissue transglutaminase, TTGA; and gliadin, AGA) and HLA risk genotypes were analysed in 37 subjects affected by or exposed to rubella during fetal life (mean age 22.5 years). One patient had diabetes and four patients had clinical hypothyroidism at the time of the examination. ICA, IAA, GADA or IA-2 A were not detected in any of the patients, while five patients tested positive for TPO antibodies. Coeliac disease or TTGA were not observed. Eight patients carried the HLA-DR3-associated HLA-DQB1*02-DQA1*05 haplotype. These results provide no evidence of an increased frequency of markers for humoral beta-cell autoimmunity in patients with CRS suggesting that diabetes in CRS may be caused by other than autoimmune mechanisms.

Long-term survival and health-related quality of life of patients with ruptured abdominal aortic aneurysm.

INTRODUCTION: the outcome of ruptured abdominal aortic aneurysm (RAAA) patients is most frequently measured as operative or in-hospital mortality rate. However, survival alone is not an indicator of quality of the treatment. Assessment of quality of life (QoL) is used increasingly and is a relevant measure of outcome. OBJECTIVE: to assess long-term survival and QoL of patients undergoing repair of RAAA. DESIGN: follow-up study with cross-sectional QoL evaluation. MATERIALS AND METHODS: between 1996 and 2000, 199 of 220 patients with RAAA underwent surgery. Survivors were sent the generic the RAND 36-item Health Survey (RAND-36) self-administered questionnaire. RESULTS: total hospital mortality and operative mortality were 103 of 220 (47%) and 82 of 199 (41%). Of the 117 initial survivors, 21 were deceased at the time of the study. When compared to an age- and sex-adjusted general population, only physical functioning was significantly impaired (p=0.01) in the 82 of 93 (88%) RAAA survivors who responded. CONCLUSIONS: survivors after repair of RAAA had almost the same QoL as the norms of an age- and sex-adjusted general population, justifies an aggressive operative policy in RAAA.

Signs of beta-cell autoimmunity and HLA-defined diabetes susceptibility in the Finnish population: the sib cohort from the Type 1 Diabetes Prediction and Prevention Study.

AIMS/HYPOTHESIS: To assess the role of HLA-defined genetic diabetes susceptibility in the appearance of signs of beta-cell autoimmunity in a series of children derived from the general population. METHODS: Tests for five HLA DQB1 alleles and four diabetes-associated autoantibodies were carried out on 1,584 older sibs of infants with an increased HLA-defined genetic risk of Type 1 diabetes. The DQB1 genotypes were classified into those conferring high (* 02/0302), moderate (* 0302/x; where x indicates * 0302 or a non-defined allele), low (* 0301/0302, * 02/0301, * 02/x, * 0302/0602, * 0302/0603; where x indicates * 02 or a non-defined allele) or decreased risk (other genotypes). RESULTS: Both islet cell antibodies (ICA) and GAD65 antibodies (GADA) were more frequent among the sibs with the high-risk genotype than among those with a low or decreased risk. Insulin autoantibodies and IA-2 antibodies (IA-2A) were more prevalent in the high-risk than low-risk sibs. Sibs with moderate-risk genotypes tested positive for ICA, GADA and IA-2A more often than sibs with genotypes conferring decreased risk. Autoantibody titres were also dependent on the genetic risk with high risk sibs having the highest values. Sibs carrying high-risk or moderate-risk genotypes tested positive for multiple antibodies (> or =2) more often than did the sibs with low or decreased genetic risk. CONCLUSIONS/INTERPRETATION: The data show that HLA-defined susceptibility to Type 1 diabetes has an effect on both the quality and quantity of humoral beta-cell autoimmunity in unaffected children derived from the general population.

Polymorphism in the peroxisome proliferator-activated receptor-gamma gene in women with polycystic ovary syndrome.

BACKGROUND: In view of the strong evidence implicating peroxisome proliferator-activated receptor-gamma (PPARgamma) in adiposity and insulin resistance a study was carried out to investigate PPARgamma genotype frequencies in women with polycystic ovary syndrome (PCOS) and to elucidate its role in the pathogenesis of the syndrome. METHODS: The study involved 135 women with PCOS and 115 healthy control women who were genotyped for a known functional variant of the PPARgamma gene using single strand conformation polymorphism (SSCP) analysis. RESULTS: A significantly different allele distribution of the Pro12 Ala polymorphism of the PPARgamma gene was observed between the two groups, with the frequency of the variant Ala isoform being significantly reduced in the PCOS group (12.6%) when compared with the control group (19.1%) (P = 0.045), at an odds ratio of 0.609 (95% confidence interval: 0.374-0.991). The genotype distributions of the Pro12 Ala polymorphism in the PCOS and control groups were different with borderline significance (P = 0.051). CONCLUSIONS: Our data support a role for PPARgamma gene polymorphism in the pathogenesis of PCOS, the presence of the Ala isoform being protective against the development of PCOS.

First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes.

AIMS/HYPOTHESIS: A reduced first-phase insulin response to intravenous glucose is perceived as a sign of far-advanced deterioration of beta-cell function during the development of Type I (insulin-dependent) diabetes mellitus, but data on insulin responses at the onset of diabetes-related autoimmunity are lacking. We studied the first-phase insulin responses of small children soon after observed seroconversion to autoantibody positivity. METHODS: In the Type I Diabetes Prediction and Prevention Study newborn infants are screened for HLA-DQB1-associated genetic risk for Type I diabetes and those with increased risk are followed-up for the emergence of islet-cell antibodies. If antibodies are detected, autoantibodies to three other antigens (insulin, GAD65 and IA-2) are also measured. To measure first-phase insulin responses, intravenous glucose tolerance tests were carried out in 52 (1 to 5-year-old) children who had recently seroconverted to islet-cell antibody positivity. RESULTS: The first-phase insulin response was subnormal (<38 mU/l, the 5(th) percentile of insulin responses of 20 islet-cell antibody negative healthy children at this age) in 22 of the 52 children (42%). Stepwise multiregression analysis showed that islet-cell antibody greater than 20 JDFU (p=0.0005), insulin autoantibodies (p=0.0009) and an increasing number of positive autoantibodies (p=0.0011) were independent predictors of low first-phase insulin response. CONCLUSION/INTERPRETATION: A decreased first-phase insulin response could be an early phenomenon in the course of prediabetes in young children, implying a rapid autoimmune destruction or loss of function of beta cells as well as possible metabolic compensation mechanisms, since 11 out of the 22 high risk children remain nondiabetic for a considerable period of time despite low insulin responses.

Lack of association between C-850T polymorphism of the gene encoding tumor necrosis factor-alpha and polycystic ovary syndrome.

In the present study, we determined whether genetic variability in the gene encoding tumor necrosis factor-alpha (TNF-alpha) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS). The study involved 87 Caucasian Finnish women with PCOS and 115 healthy control women who were genotyped for the C-850T polymorphism in the TNF-alpha gene promoter. Analysis by chi(2) was used to assess genotype and allele frequency differences between PCOS women and controls. A similar genotype distribution for the C-850T polymorphism was observed in the two groups, with the frequency of the variant T allele being 8.6% in the PCOS group and 9.6% in the control group (p = 0.862). Accordingly, the profile of genotype frequencies was similar in the groups. The observed profiles of allele and genotype frequencies confirm an equilibrium state between C-850T polymorphism and PCOS and suggest that polymorphism of the TNF-alpha gene is unlikely to contribute to the risk of PCOS.

Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population.

The aim of this study was to evaluate the frequency and predictive value of diabetes-associated autoantibodies, such as islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD65 (GADA), and the IA-2 molecule (IA-2A) in genetically susceptible children from the general population during the first 2 yr of life. Of 12,170 newborn infants, 1,005 with increased genetic risk of type 1 diabetes (high risk, human leukocyte antigen DQB1*02/*0302; moderate risk, DQB1*0302/x, where x = other than *02, *0301, or *0602) were monitored for ICA, IAA, GADA, and IA-2A at 3- to 6-month intervals from birth up to a minimum age of 2 yr. In addition, all 15 genetically susceptible children from the general population who had participated in regular immunological follow-up and developed clinical type 1 diabetes by the end of April 2000 were analyzed for the development of autoantibodies. Among 1,005 children, 63 (6.3%) tested positive for at least one autoantibody, 31 for ICA (3.1%), 48 for IAA (4.8%), 23 for GADA (2.3%), and 13 for IA-2A (1.3%) at least once by the age of 2 yr. Both ICA and IAA identified 95% [95% confidence interval (CI), 77.2-99.9%] of those who tested persistently positive for multiple (> or = 2) antibodies at the age of 2 yr, GADA identified 86% (CI, 65.1-97.1%), and IA-2A identified 55% (CI, 32.2-75.6%). Close to half of the antibody-positive children (29 of 63) reverted back to antibody negativity. Autoantibodies disappeared more often among those who tested positive for IAA than among those who tested positive for other autoantibodies (P < or = 0.021). Among the 15 children who developed type 1 diabetes, the disease sensitivity of ICA was 80% (CI, 51.9-95.7%), that of IAA was 93% (CI, 68.0-99.8%), that of GADA was 60% (CI, 32.3-83.7%), and that of IA-2A was 40% (CI, 16.3-67.7%). These results suggest that IAA are characterized by high sensitivity, early appearance, and high frequency of transient antibody positivity, whereas ICA detected with a thoroughly standardized assay appear to be more specific for the screening of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes in the Finnish population, which has the highest incidence of type 1 diabetes in the world.

Rotavirus infections and development of diabetes-associated autoantibodies during the first 2 years of life.

Rotavirus, the most common cause of childhood gastroenteritis, has been implicated as one of the viral triggers of diabetes-associated autoimmunity. To study the possible association between rotavirus infections and the development of diabetes-associated autoantibodies, we measured the prevalence of rotavirus antibodies in serum samples collected at 3-6-month intervals up to the age of 2 years from 177 children selected from consecutive newborns because they carried HLA-DQB1 alleles associated with increased risk for type 1 diabetes. Twenty-nine of the children developed at least two of four diabetes-associated autoantibodies (ICA, IAA, GADA or IA-2A) during the first 2 years of life (the cases), whereas 148 children remained autoantibody-negative matched with the cases for date of birth, gender, living region and HLA-DQB1 alleles. The temporal association between the development of the first-appearing diabetes-associated autoantibody and rotavirus infections was studied by analysing whether the cases had a diagnostic increase in rotavirus antibody titre more often during the 6-month period that preceded seroconversion to autoantibody positivity than the controls. By the age of 12 months one of the 13 case children (7%), who had a serum sample drawn at that age and who had developed at least one type of diabetes-associated autoantibodies, had experienced a rotavirus infection, while 12 of the 61 (20%) autoantibody-negative control children had had a rotavirus infection. By 18 months, four of the 22 autoantibody-positive cases (18%) and 18 of the 89 controls (20%) had rotavirus antibodies, and by the age of 24 months the respective numbers were five of the 27 cases (19%) and 32 of the 113 (28%) controls. A rotavirus infection occurred during the 6 months preceding the sample which was positive for an autoantibody in four of the 25 periods (16%) for which both necessary samples were available, while the controls had a rotavirus infection during 55 of the 370-such periods (15%). Accordingly, our data suggest that rotavirus infections are unlikely triggers of beta-cell autoimmunity in young children with genetic susceptibility to type 1 diabetes.

Apolipoprotein E alleles in women with polycystic ovary syndrome.

OBJECTIVE: To investigate the frequency of apoE alleles among women with polycystic ovary syndrome. DESIGN: Retrospective case-control study. SETTING: University-based endocrinology/infertility clinic. PATIENT(S): Healthy fertile women (n = 91) and women with a diagnosis of polycystic ovary syndrome (n = 58). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The presence of the three most common apoE alleles (epsilon2, epsilon3, and epsilon4) determined by polymerase chain reaction-restriction fragment length polymorphism in the two groups and in the general population in our area. RESULT(S): The frequency of the apo epsilon4 allele was 17.2% among women with polycystic ovary syndrome and was 18.7% among healthy fertile women, which is close to the rate in the general population in our area (19%). None of the apoE genotypes (Fisher's exact test; P=.71) or alleles (P=.78) was significantly overrepresented, and the homozygous genotype epsilon4 was not associated with the clinical disease. CONCLUSION(S): The observed profiles of allele and genotype frequencies confirm the equilibrium state between apoE polymorphism and polycystic ovary syndrome and suggest that apoE does not play a major role in the development of hyperlipidemia in the group of women with polycystic ovary syndrome.

Feasibility of genetic and immunological prediction of type I diabetes in a population-based birth cohort.

AIMS/HYPOTHESIS: Population-wide genetic screening of susceptibility to multifactorial diseases will become relevant as knowledge of the pathogenesis of these diseases increases and preventive interventions are identified. METHODS: Feasibility and acceptance of neonatal genetic screening for Type I (insulin-dependent) diabetes mellitus susceptibility and adherence of the at-risk children to frequent autoantibody follow-up were studied. Screening was offered to all families. The infants with HLA-DQB1 genotypes *02/*0302 and *0302/x (x not equal to *02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of beta-cell autoimmunity were invited to a separate prevention trial. RESULTS: The parents of 31,526 babies born between November 1994 and April 1999 (94.4% of those eligible) agreed to genetic screening. We found that 4651 infants (14.8%) had increased genetic risk (2.5 to 15 times that of the general population) for Type I (insulin-dependent) diabetes mellitus, and 80% of them joined the autoantibody surveillance. At the age of 1, 2, 3 and 4 years, 74, 69, 68 and 76% of the at-risk children, respectively, attended the follow-up. A total of 17 of the 22 children (77%) who were born during the study period and have developed diabetes carry the risk genotypes we currently use for screening. CONCLUSIONS/INTERPRETATION: Population-based screening of genetic susceptibility for Type I diabetes, linked with a possibility to participate later in a prevention trial, is highly accepted in Finland and identifies about 75% of those developing diabetes at an early age. Families adhere well to the frequent measurement of signs of beta-cell autoimmunity in the children at-risk.

Relationship of the metabolic syndrome and obesity to polycystic ovary syndrome: a controlled, population-based study.

OBJECTIVE: Although hyperinsulinemia seems to be an essential feature of polycystic ovary syndrome, the frequency of gynecologic disorders related to polycystic ovary syndrome at a population level in women with evident metabolic syndrome is not known. STUDY DESIGN: We conducted a cross-sectional, population-based study. Participants (N = 204) were recruited from a random sample of women in 5 age groups (range, 35-54 years) living in a defined area. Metabolic syndrome was considered to be present if 3 of the following 8 criteria were fulfilled: (1) first-degree relative with type II diabetes, (2) body mass index > or = 30 kg/m2, (3) waist/hip ratio > or = 0.88, (4) blood pressure > or = 160/95 mm Hg or drug treatment for hypertension, (5) fasting serum triglyceride level > or = 1.70 mmol/L, (6) high-density lipoprotein cholesterol value < 1.20 mmol/L, (7) abnormal glucose metabolism, and (8) fasting insulin value > or = 13.0 mU/L. The frequency of metabolic syndrome was 106 (19.5%) of 543 cases. The control group consisted of 62 overweight women without central obesity or metabolic syndrome and 53 healthy lean women (body mass index < 27 kg/m2. RESULTS: The group with metabolic syndrome differed from the other women according to most of the selection criteria and also had the highest free testosterone concentration. However, there were no differences between the groups regarding parity, infertility problems, or obstetric outcome. However, oligomenorrhea appeared to be more common in women with metabolic syndrome, especially in those with more severe symptoms (46.2%), than in obese (25.4%) and lean (15.1%) control subjects. Polycystic-like ovaries were detected by vaginal ultrasonography with similar frequency (13.1%, 15.3%, and 13.2% in women with metabolic syndrome, obese women, and lean women, respectively). CONCLUSIONS: Surprisingly few women with metabolic syndrome had symptoms suggestive of polycystic ovary syndrome, in comparison with obese and lean women. Our results suggest that at the population level polycystic ovary syndrome only accounts for a distinct subgroup of a much wider problem, metabolic syndrome.