Kaori Ohta

Antiphospholipid antibodies increase the risk of pregnancy-induced hypertension and adverse pregnancy outcomes

Antiphospholipid antibody (aPL) is associated with thromboembolism. There is scant evidence of a relationship between the aPL profile and serious adverse pregnancy outcome. The aim of this study was to assess whether aPL measurements during early pregnancy were useful in predicting a serious adverse pregnancy outcome. In this prospective study, we measured aPLs, including lupus anticoagulant (LA), IgG, IgM, IgA anticardiolipin antibody (aCL), IgG, IgM phosphatidylserine-dependent antiprothrombin antibody, and IgG kininogen-dependent antiphosphatidylethanolamine antibody (aPE) during the first trimester in a consecutive series of 1155 women. The 99 th percentile cut-off values in each aPL were determined using samples from 105 women who did not exhibit any pregnancy morbidity. We assessed the predictive risk of a serious adverse pregnancy outcome adjusted for confounding factors. We found that IgG aCL was associated with developing pregnancy-induced hypertension (PIH) (odds ratio 11.4, 95% CI 2.7-48); IgG aPE with PIH (8.3, 2.4-29), severe PIH (20.4, 4.5-91), and premature delivery (PD) (12.7, 3.1-50); and LA with PD (11.0, 2.8-44) and low birth weight (8.0, 2.1-31). The combinations of IgG aPE plus IgG aCL (17.5, 4.7-66.7) or IgG aPE plus LA (22.2, 5.4-909) measurements predicted severe PIH with 30.8% sensitivity and 99.2% specificity. We conclude that aPL measurements during early pregnancy may be useful in predicting adverse pregnancy outcome.

Dietary habits and risk of ossification of the posterior longitudinal ligaments of the spine (OPLL); findings from a case-control study in Japan.

The relation between dietary habits and the risk of ossification of the posterior longitudinal ligaments of the spine (OPLL) was investigated in a case-control study conducted in Japan from 1998 to 2001. Prevalent OPLL cases (n = 69) were identified and individually matched by age and sex with community controls (n = 138) randomly selected from the general population in Hokkaido. A self-administered food-frequency questionnaire was used to assess habitual dietary intake. The odds ratio (OR) and its 95% confidence interval (CI) were estimated, using conditional logistic regression models to compute the OR adjusted for a history of diabetes mellitus. We found that frequent consumption of pickles (salted products) was significantly associated with an increased risk of OPLL, with an adjusted OR of 1.6 (95% CI, 1.1 to 2.2). The adjusted OR for nondaily consumers of rice was 3.0 (95% CI, 2.4 to 3.7). Frequent consumption of chicken (adjusted OR, 0.5; 95% CI, 0.3 to 0.98) and soy foods (adjusted OR, 0.4; 95% CI, 0.2 to 0.7) was significantly associated with a decreased risk of OPLL. Our findings suggest that dietary habits may constitute independent risk factors for OPLL. Further studies will be needed to prospectively determine the relationship between dietary habits and OPLL risk.

High body mass index after age 20 and diabetes mellitus are independent risk factors for ossification of the posterior longitudinal ligament of the spine in Japanese subjects: a case-control study in multiple hospitals.

Study Design. A sex- and age-matched case-control study was carried out. Objectives. To facilitate early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament of the spine, the authors analyzed histories of past illness, past body mass indexes, and body pliableness by nature, adjusted for other factors considered to be risk factors. Summary of Background Data. The cause of ossification of the posterior longitudinal ligament of the spine has not yet been elucidated in detail, although many possible causative factors have been suggested, including gender, diabetes mellitus, trauma, hormonal imbalance, and dietary habits. Methods: A self-administered questionnaire was obtained from 69 patients with ossification of the posterior longitudinal ligament of the spine and 138 sex- and age-matched control participants who were free of spinal disease, randomly selected from participants in a health checkup in a town. After univariate analysis, a stepwise method was applied to select significant factors in multivariate analysis. Results. A multivariate analysis revealed that the following three indicators were independent potent risk factors for ossification of the posterior longitudinal ligament of the spine: history of diabetes mellitus, history of lumbago, and maximum body mass index before manifestation ≥25, after adjustment for other possible lifestyle risk factors. Conclusion. Excessive weight gain between 20 and 40 years of age, diabetes mellitus, and lumbago were found to be independent risk factors for ossification of the posterior longitudinal ligament of the spine. Follow-up studies, including the addition of hospital-based control participants and analysis of genetic polymorphisms, will be needed in the future.

Analysis of the geographical accessibility of neurosurgical emergency hospitals in Sapporo city using GIS and AHP

To improve the geographical accessibility of neurosurgical emergency hospitals for elderly people, we developed several alternative site plans for a new neurosurgical emergency hospital in Sapporo, Japan. Hospitals, population data, routes, and the numerical information for the Analytic Hierarchy Process computations were input into a Geographical Information System. Pairwise comparison revealed the following weights which were assigned to each of the four criteria: 0.674 for availability of hospital beds; 0.169 for the maximum road distance of the shortest routes; 0.101 for the elderly population within a 3‐km radius; and 0.056 for the median road distance of the shortest routes. The alternative proposed could cover 4000 more elderly people in the 3‐km radius of the hospitals. The integration of Geographical Information Systems and the Analytic Hierarchy Process constitutes a powerful tool for analysing traffic conditions in mid‐sized cities and for suggesting city planning to improve prognosis of stroke.

A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene

AbstractHypertension in pregnancy (HP) is a multifactorial disease manifested due to a complex combination of environmental factors and several predisposing genes including factors in the renin angiotensin system. The aim of this study was to assess the association between the A1166C variant of the angiotensin II type 1 receptor (AT1) gene and severe HP. We carried out association studies and multivariate analyses including other candidate causal factors of HP such as the M235T variant of the angiotensinogen (AGT) gene, prepregnancy body mass index (BMI), and family history of hypertension in Japanese subjects. One hundred and fourteen patients with severe HP and 291 normal pregnancy controls were genotyped. Among primiparous subjects, the frequency of “AC+CC genotype of AT1” was significantly higher in severe HP than in the controls. A multivariate analysis with “AC+CC genotype of AT1” and “TT genotype of AGT” revealed that these were independently associated with primiparous severe HP. However, when “family history of hypertension” and “prepregnancy BMI ≥25” were added as factors examined in the multivariate analysis, only “TT genotype of AGT” and “family history of hypertension” were found to be independent potent factors. The present results suggest that the C1166 allele of the AT1 gene may be concerned with the predisposition to essential hypertension independently of the T235 allele of the AGT gene.

Anti-β2 glycoprotein-I antibody increases the risk of pregnancy-induced hypertension: a case-controlled study.

The aim of this study was to evaluate whether anti-beta2 glycoprotein-I antibody (anti-beta2GPI) of the IgG or IgM classes is associated with the development of pregnancy-induced hypertension (PIH) or preeclampsia in the Japanese population. In a case-controlled cohort study, peripheral blood was obtained at 8-14 weeks of gestation from a consecutive series of 1155 women. The case group comprised 36 patients who later developed PIH during the pregnancy. Of the 36 PIH patients, 13 had severe PIH, 18 had preeclampsia and 11 had severe preeclampsia. One hundred and eleven age- and parity-matched women whose pregnancies ended in normal delivery without obstetric complications were selected as controls. We found that a titer of anti-beta2GPI IgG>or=1.0 U/ml was a risk factor for severe PIH (P=0.023, OR 5.7 95%CI 1.4-22.8). In addition, titers of anti-beta2GPI IgM>or=1.2 U/ml was found to be a risk factor for PIH (P=0.001, OR 8.8 95%CI 1.6-47.5). In women positive for anti-beta2GPI but negative for lupus anticoagulant, anti-cardiolipin, phosphatidylserine-dependent anti-prothrombin, or kininogen-dependent anti-phosphatidylethanolamine antibodies, the presence of anti-beta2GPI was not a significant risk factor for development of PIH or preeclampsia. In conclusion, the presence of anti-beta2GPI antibody represents a risk factor for developing PIH and severe PIH. This finding supports the utility of anti-beta2GPI determination as one of the laboratory criteria for anti-phospholipid syndrome classification. The usefulness of anti-beta2GPI measurement among women without other anti-phospholipid antibodies requires further study.

FokI variant of vitamin D receptor gene and factors related to atherosclerosis associated with ossification of the posterior longitudinal ligament of the spine: a multi-hospital case-control study.

Study Design. A sex- and age-matched case-control study with genotyping of the FokI variant of the vitamin D receptor gene (VDR) was carried out. Objectives. To facilitate the early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament (OPLL) of the spine, we analyzed the FokI variant of VDR and past body mass indexes, histories of past illness, family history, and body pliability along with lifestyle factors. Summary of Background Data. Many possible genetic and environmental risk factors for OPLL have been suggested, including male sex, high body mass index, diabetes mellitus, trauma, hormonal imbalance, and dietary and sleeping habits and genetic variants. Methods. Both a self-administered questionnaire and whole blood samples were obtained from 63 patients with OPLL and 126 sex-, age-, and hospital-matched controls free of backbone diseases were randomly selected from hospital patients. VDR genotyping was carried out using PCR-RFLP methods. After univariate analysis, multivariate and subgroup analyses according to the VDR genotype was applied to clarify the confounding relationship between VDR genotype and other possible risk factors. Results. A multivariate analysis revealed that the VDR FF genotype, family history of myocardial infarction, high body mass index at age 40, long working hours, and working with night shift to be independent potent risk factors for OPLL. Conclusion. The risk of developing OPLL may possibly be reduced gradually and effectively by removing or minimizing the effect of such lifestyle factors one at a time through targeted preventive intervention.

4G/5G variant of plasminogen activator inhibitor-1 gene and severe pregnancy-induced hypertension: subgroup analyses of variants of angiotensinogen and endothelial nitric oxide synthase.

Background Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3). Methods An association study of PAI-1 polymorphism, and subgroup analyses of common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy pregnant controls. Results No significant differences were found between the cases and controls in the frequencies of allele 4G or the 4G/4G genotype. In subgroup analyses, after adjustment for multiple comparison, a significant association with the AGT TT genotype was found among women with the PAI-1 4G/4G genotype, and an association with the NOS3 GA+AA genotype was found among women with the 5G/5G or 4G/5G genotypes. Conclusions Our findings suggest that there are at least 2 pathways in the pathogenesis of severe PIH. However, with respect to early prediction and prevention of severe PIH, although the PAI-1 4G/4G genotype alone was not a risk factor for severe PIH, the fact that PAI-1 genotypes are associated with varying risks for severe PIH suggests that PAI-1 genotyping of pregnant women, in combination with other tests, may be useful in the development of individualized measures that may prevent severe PIH.