Immunoregulatory gene polymorphisms in Japanese women with preterm births and periodontitis

Many studies have reported an association between periodontal disease and preterm birth, although this remains controversial. Cytokines and antibodies produced to give resistance to infection can enter the bloodstream and cause preterm labor. We analyzed maternal genetic polymorphisms in various immunoregulatory genes that could affect both preterm birth and periodontitis. A total of 1099 women referred to the Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital were candidates for participation, 424 of whom refused, and 553 were excluded. The final number of subjects was 122 (51 with preterm birth, 71 with term birth). Genomic DNA was isolated from venous blood, and 22 polymorphisms were determined: IL-1A, IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, TNFA, TNFRI, TNFRII, FcγRIIA, FcγRIIB, FcγRIIIA, FcγRIIIB, and FcαR. Within five days of labor, periodontal parameters were evaluated, and bacteria from subgingival plaque were detected using real-time PCR. There was no difference in the prevalence and degree of periodontitis between term and preterm births. Chi-squared tests showed that an age <33 years and FcαR(+56)T/C alleles were associated with preterm birth. Multiple logistic regression analysis represented a model with significant fitness in which four variables were associated with preterm birth: maternal age, number of Aggregatibacter actinomycetemcomitans, IL-6(-572)G/C, and FcαR(+56)T/C. In conclusion, there was no association between preterm birth and periodontitis in this study. A. actinomycetemcomitans, IL-6, and FcαR were suggested to be associated with preterm birth. Multiple logistic regression models with both genetic and environmental factors would be useful for evaluating susceptibility to preterm birth.     

Differential diagnosis of the infundibular dilation and aneurysm of internal carotid artery: assessment with fusion imaging of 3D MR cisternography/angiography

Fusion imaging of 3D MR cisternography/angiography was used for the assessment of the vascular bulging finding detected by MR angiography from the viewpoint of the outer wall configuration of the corresponding internal carotid artery depicted by MR cisternography. With a fusion image, useful information was obtained to distinguish an infundibular dilation and enlarged origin of the normal posterior communicating artery from an aneurysm. This imaging technique can be a feasible addition to a noninvasive screening of cerebrovascular lesions with MR angiography alone.     

The Effect of a Selective Inhibitor of Phosphodiesterase‐9 on Oxidative Stress,Inflammation and Cytotoxicity in Neutrophils from Patients with Sickle Cell Anaemia

The aim of the study was to investigate the possible anti‐inflammatory and antioxidant effects of BAY 73‐6691 on neutrophils from SCA patients. This study included 35 patients with a molecular diagnosis of SCA, whose neutrophils were isolated and treated with BAY 73‐6691 at the concentrations 100, 10, 1.0 and 0.1 μg/mL. LDH release and MTT assays were performed to verify cell viability. To evaluate oxidative stress, the following parameters were determined by spectrophotometric assays: NO and malondialdehyde (MDA) levels and activity of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx). As inflammatory markers, myeloperoxidase (MPO) levels were evaluated by colorimetric assay and TNF‐α by enzyme immunoassay. The results showed that neutrophils from SCA patients not treated with hydroxyurea (HU) had significantly lower NO levels and catalase and SOD activity, as well as significantly higher MDA, MPO and TNF‐α levels when compared with neutrophils from SCA patients treated with HU and neutrophils from control group. Treatment of SCA neutrophils with BAY 73‐6691 resulted in 94%, 200% and 168% increase in NOx levels, SOD and catalase activity, respectively. In addition, there was a reduction of approximately 46% and 45% in TNF‐α and MPO levels, respectively. In SCAHU neutrophils, there was a 30% and 44% increase in NOx levels and SOD activity, respectively, and a 28% and 37% decrease in TNF‐α and MPO levels, respectively. However, these effects were observed at cytotoxic doses only. The results of this study are original and demonstrate that inhibition of phosphodiesterase‐9 in neutrophils from SCA patients with BAY 73‐6691 was able to increase the NO bioavailability and attenuate oxidative stress and inflammation in neutrophils from patients not treated with HU.     

Transesophageal Echocardiographic Findings Are Independent and Relevant Predictors of Ischemic Stroke in Patients with Nonvalvular Atrial Fibrillation

Background and Purpose

Not only clinical factors, including the CHADS₂ score, but also echocardiographic findings have been reported to be useful for predicting the risk of ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF). However, it remains to be determined which of these factors might be more relevant for evaluation of the risk of stroke in each patient.

Methods

In 490 patients with NVAF who underwent transesophageal echocardiography (TEE), we examined the long-term incidence of ischemic stroke events (mean follow-up time, 5.7±3.3 years). For each patient, the predictive values of gender, the CHADS₂ risk factors (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, history of cerebral ischemia), the CHADS₂ score, and the findings on echocardiography, including TEE risk markers, were assessed.

Results

The ischemic stroke rate was significantly correlated with the CHADS₂ score (p<0.05). According to the results of univariate analyses, age ≥75 years, history of cerebral ischemia, CHADS₂ score ≥2, and presence of TEE risk were significantly correlated with the incidence of ischemic stroke. Cox proportional hazards regression analyses identified age ≥75 years and presence of TEE risk as significant predictors of subsequent ischemic stroke events in patients with NVAF. As compared with that in persons below 75 years of age without TEE risk, the ischemic stroke rate was significantly higher in persons who were ≥75 years of age with TEE risk (4.3 vs. 0.56%/year, adjusted hazard ratio=8.94, p<0.001).

Conclusions

TEE findings might be more relevant predictors of ischemic stroke than the CHADS₂ score in patients with NVAF. The stroke risk was more than 8-fold higher in patients aged ≥75 years with TEE risk.     

Circulating hematopoietic stem cells in patients with idiopathic choroidal neovascularization

PURPOSE: In a prior study, the correlation was investigated between circulating hematopoietic stem cells (HSCs) and the activity or severity of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). The present study was designed to explore the role of circulating HSCs in the pathogenesis of CNV in patients with idiopathic (i)CNV. METHODS: Thirteen patients with clinically documented iCNV and 10 age-sex matched patients without iCNV or systemic disease were enrolled in a case-control study. Circulating HSCs were collected from the patients' peripheral blood and cultured. Colony-forming capacity, migration activity, and invasion activity of HSCs were experimentally analyzed. RESULTS: Colony-forming units by Hill's assay (CFU-Hill) were markedly lower (P<0.001) in patients with iCNV (12.8+/-3.2) than in healthy patients (67.6+/-12.6). Invasion activities of HSCs were reduced significantly in patients with iCNV. CFU-Hill was impaired in the patients (4.0+/-1.2) with CNV more than 1500 microm compared with the patients (20.3+/-4.0) with CNV less than 1500 microm (P=0.006). CONCLUSIONS: Similar to the previous finding of CNV associated with AMD, impaired functional activities of circulating HSCs were observed in patients with iCNV, which correlated with the size of iCNV. These results in young patients provide evidence to support the role of circulating HSCs in the pathogenesis of CNV.     

Clinical risk factors for poor neonatal outcomes in umbilical cord prolapse

Objectives: To clarify the clinical risk factors associated with poor neonatal outcomes due to umbilical cord prolapse (UCP).

Methods: A postal questionnaire survey was attempted in Japan. The clinical risk factors and managements associated with poor neonatal outcomes were analyzed in cases of UCP treated in Japan.

Results: A total of 267 cases of UCP (out of 2?037?460 total deliveries) were analyzed. The rates of intrauterine death, neonatal death and survival with disability were 3.4%, 5.6% and 7.1%, respectively. The multivariate regression analysis for these poor neonatal outcomes revealed that the significant risk factors included a prolapsed amniotic sac (adjusted odds ratio (aOR), 4.49), preterm labor (aOR, 2.99) and replacement of the prolapsed umbilical cord into the uterus (aOR, 2.87). However, UCP that occurred during labor (aOR, 0.28) and emergency cesarean section (aOR, 0.11) were associated with a reduction in the rates of poor outcomes. The interval between the diagnosis of UCP and delivery was significantly longer in the infants with a poor outcome than intact survival (median 30 versus 24?min, p?=?0.048).

Conclusion: An emergency cesarean section should be carried out immediately to ensure a better outcome for the infant.