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Open repair for infra-renal abdominal aortic and iliac artery aneurysms (AAAs) is a robust treatment. On the other hand, endovascular aneurysm repair (EVAR) has been widespread because of its less invasiveness. However, patients after EVAR frequently require postoperative radiographic examinations and may feel anxiety for their endoleaks. We prospectively evaluated Health-related Quality of Life of the patients with these two fashions using the 8-item Short Form (SF-8). From 2011 to 2013, 89 consecutive elective cases of AAAs were treated. They were prospectively divided into EVAR and open repair groups but not randomly. The exclusion criteria were as follows: perioperative status for other surgeries, infectious aneurysm, severely deteriorated conditions, and patients who cannot answer for these questionnaire or show their consent. The SF-8 questionnaire was completed through interviews preoperatively, and at 1, 3, 6, and 12 months after treatment. The SF-8 questionnaire was completed for 55 cases [EVAR group (ER): 25, open repair group (OR): 30]. There was no significant difference between these groups regarding patients' characteristics except congestive heart disease. The preoperative scores of the SF-8 were similar in both groups except physical function and social function, which were lower in ER (p < 0.05). There was no operative death in both groups. Operative duration and hospital stay in EVAR were significantly shorter than those in OR (p < 0.05). Follow-up rate at 1, 3, 6, and 12 months was 100, 100, 68.0, and 64.0% in ER, and 100, 90.0, 80.0, and 66.6% in OR, respectively. During follow-up, both groups had no AAAs associated death. Regarding changes of the SF-8 scales, there were some trends at physical component summary score (PCS) and mental component summary score (MCS) in ER. The PCS decreased at 1 month, gradually increased at 3 months, and levelled off until 12 months. The MCS increased at 1 and 3 months, but gradually went down and almost stayed at the same level as preoperative one at 12 months. In OR, PCS and MCS decreased at 1 month and after that increased gradually at 3 and 6 months, and stayed the same at 12 months. The MCS recovered to preoperative score earlier than the PCS. In this study, EVAR did not show any significant mental disturbance based on the SF-8 for 1-year comparing to open repair.

Hypothalamic insulin receptor signaling regulates energy balance and glucose homeostasis via agouti-related protein (AgRP). While protein tyrosine phosphatase 1B (PTP1B) is classically known to be a negative regulator of peripheral insulin signaling by dephosphorylating both insulin receptor β (IRβ) and insulin receptor substrate, the role of PTP1B in hypothalamic insulin signaling remains to be fully elucidated. In the present study, we investigated the role of PTP1B in hypothalamic insulin signaling using PTP1B deficient (KO) mice in vivo and ex vivo. For the in vivo study, hypothalamic insulin resistance induced by a high-fat diet (HFD) improved in KO mice compared to wild-type (WT) mice. Hypothalamic AgRP mRNA expression levels were also significantly decreased in KO mice independent of body weight changes. In an ex vivo study using hypothalamic organotypic cultures, insulin treatment significantly increased the phosphorylation of both IRβ and Akt in the hypothalamus of KO mice compared to WT mice, and also significantly decreased AgRP mRNA expression levels in KO mice. While incubation with inhibitors of phosphatidylinositol-3 kinase (PI3K) had no effect on basal levels of Akt phosphorylation, these suppressed insulin induction of Akt phosphorylation to almost basal levels in WT and KO mice. The inhibition of the PI3K-Akt pathway blocked the downregulation of AgRP mRNA expression in KO mice treated with insulin. These data suggest that PTP1B acts on the hypothalamic insulin signaling via the PI3K-Akt pathway. Together, our results suggest a deficiency of PTP1B improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under HFD conditions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Silicone oil (SO) is an intraocular surgical adjuvant that reduces the surgical complications in refractory retinal diseases, although membrane and cellular proliferation is often seen even in SO-filled eyes. We hypothesised that the fluid in the space between the SO and the retina, named the "sub-silicone oil fluid (SOF)", enhances these biological responses. We proposed a safe method for SOF extraction. We also analysed inflammatory cytokine expressions and SOF osmotic pressures from eyes with rhegmatogenous retinal detachment (RRD), proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular hole-associated retinal detachment (MHRD). Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD. Fibroblast growth factor-2, IL-10, IL-12p40, IL-8, VEGF, and transforming growth factor beta 1 levels in eyes with exacerbated PDR indicated a significantly higher expression than those with simple PDR. IL-6 and tumour necrosis factor alpha in eyes with exacerbated PVR demonstrated a significantly higher expression than in those with simple PVR. However, there was no difference in SOF osmotic pressure between group of each disease. These studies indicate that disease-specific SOF is a significant reflection of disease status.

Polypoidal choroidal vasculopathy (PCV) is characterized by polyp-like choroidal neovascularization and a branching vascular network. Intravitreal aflibercept injection (IAI) or photodynamic therapy (PDT) is used for treatment. We retrospectively compared the 1-year outcomes of IAI monotherapy and its combination with initial PDT for PCV. Twelve eyes with naïve PCV received three IAIs and a single PDT after the first IAI and as needed injection (combination group); 11 eyes with naïve PCV received three IAIs and as needed injections (IAI group). Significant improvements in visual acuity after 2 months and in CRT after 1 month were maintained at 12 months in both groups (both P < 0.05); groups did not differ significantly at any time point. CCT significantly reduced after 3 and 12 months in the combination group (both P < 0.05) but not in the IAI group. A mean of 3.7 ± 0.9 and 5.6 ± 2.0 injections was administered to the combination and IAI groups, respectively (P = 0.013). Within a 1-year period, combination therapy was found to yield similar visual acuity and retinal structure improvements and maintenance as IAI monotherapy while requiring fewer IAIs.

Regarding to coronary artery bypass grafting (CABG), the end-to-side anastomosis (ESA) has been performed as a gold standard. Recently, the effectiveness of the distal side-to-side anastomosis (SSA) in CABG using internal mammary artery has been reported. The benefit of SSA comparing to ESA also has been disclosed by computing simulation. However, use of SSA by venous conduit for individual CABG has not been reported. In this study, we investigated feasibility of SSA. From January 2013 to October 2014, we conducted 114 CABGs. There were 92 venous distal anastomoses without sequential anastomotic site (61 SSA and 31 ESA). The anastomosis was evaluated before discharge and at 1 year after the procedure by angiography or multi-detector row computed tomographic coronary angiography. The median values for time to anastomosis were 13 min in the two group (p = 0.89). There was no revision of anastomosis in both groups. Additional stitches for hemostasis were required significantly less in SSA than ESA (18.0 vs 45.2 %, respectively, p < 0.05). Early angiographic patency; 96.6 % for SSA vs 93.5 % for ESA (p = 0.50), and percentage of good anastomotic figure; 91.2 % for SSA vs 87.1 % for ESA (p = 0.54) were similar in both groups. The angiographic patency at 1 year were 92.9 % for SSA and 81.0 % for ESA (p = 0.16). There was no predictive factor for early and late graft failure. Our study showed feasibility of SSA using venous conduit in individual CABG based on early and mid-term angiographic results. This anastomotic fashion is easy to perform and maybe beneficial in blood flow pattern.

Objectives: To identify factors that determine early saphenous vein graft failure (VGF) within 1 month after coronary artery bypass grafting (CABG)., Methods: Seven hundred forty-nine consecutive patients underwent primary isolated CABG with saphenous vein grafts at three Japanese centres from 1 January 2005 to 31 December 2014. According to angiographic findings within 1 month of CABG surgery, 63 patients (8.4%) developed early VGF. We examined the relationships between variables and early VGF by using multivariable logistic regression analysis., Results: The preoperative clinical characteristics were similar between patients with and without early VGF, except for median preoperative haemoglobin A1c levels, which were significantly higher among patients with early VGF (6.7 vs 6.4%, P = 0.046). Additionally, anastomosis to the vessel with chronic total obstruction was performed more frequently among patients with early VGF (22/63 [34.9%] vs 140/686 [20.4%], P = 0.007), and myocardial infarction during the hospital admission occurred more frequently among patients with early VGF (4/63 [6.3%] vs 2/686 [0.3%], P < 0.0001). Results of multivariable analysis showed that the preoperative haemoglobin A1c level was associated with early VGF (odds ratio per unit increase, 1.30; 95% confidence interval, 1.06-1.60; P = 0.013)., Conclusions: An increased preoperative haemoglobin A1c level was strongly associated with early VGF after CABG. Thus, VGF happened more frequently in patients with poorly controlled diabetes mellitus., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Protein tyrosine phosphatase 1B (PTP1B) regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD), remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3) was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO) on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT). In hypothalamic organotypic cultures, incubation with TNFα led to increased p-STAT3, accompanied by decreased Tnf and increased Il10 mRNA expression, in KO compared to WT. Incubation with p-STAT3 inhibitors or microglial depletion eliminated the differences in inflammation between genotypes. These data indicate an important role of JAK2-STAT3 signaling negatively regulated by PTP1B in microglia, which attenuates hypothalamic inflammation under HFD conditions., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Ocular trauma is one of the leading causes of visual impairment worldwide. Because of the popularity of cataract surgeries, aged individuals with ocular trauma commonly have a surgical wound in their eyes. The purpose of this study was to evaluate the visual outcome of cases that were coincident with intraocular lens (IOL) ejection in the eyes with ruptured open-globe ocular injuries. Consecutive patients with open-globe ocular injuries were first reviewed. Patients' characteristics, corrected distance visual acuities (CDVAs) over 3 years after the trauma, causes of injuries, traumatic wound patterns, and coexistence of retinal detachment were examined. The relationships between poor CDVA and the other factors, including the complications of crystalline lens and IOL ejection, were examined. A total of 105 eyes/patients [43 eyes with rupture, 33 with penetrating, 28 with intraocular foreign body (IOFB), and 1 with perforating injuries] were included. Rupture injuries were common in aged patients and were mostly caused by falls, whereas penetrating and IOFB injuries were common in young male patients. CDVAs of the eyes with rupture injuries were significantly worse than those of the eyes with penetrating or IOFB injuries. CDVA from more than 50% of the ruptured eyes resulted in no light perception or light perception to 20/500. CDVA of the ruptured eyes complicated by crystalline lens ejection was significantly worse than that of those complicated by IOL ejection. The wounds of the ruptured eyes complicated by IOL ejection were mainly located at the superior corneoscleral limbus, whereas those of the eyes complicated by crystalline lens ejection were located at the posterior sclera. There were significant correlations between poor CDVA and retinal detachment and crystalline lens ejection. These results proposed a new trend in the ocular injuries that commonly occur in aged patients; history of cataract surgery might affect the final visual outcome after open-globe ocular injuries., Competing Interests: The authors have declared that no competing interests exist.

Purpose. We had earlier reported positive hsa-miR-148a-3p expression in eyes with rhegmatogenous retinal detachment (RRD) and its involvement in the epithelial-mesenchymal transition of retinal pigment epithelium in vitro. Here we investigated the association of hsa-miR-148a-3p expression levels in the vitreous fluid of patients with RRD with severity of RRD. Methods. The hsa-miR-148a-3p expression levels in the vitreous fluid, range (degree) of retinal detachment (RD), and pixels of retinal break were measured in 27 eyes with RRD. The association of hsa-miR-148a-3p expression levels with other factors was evaluated by multiple regression analysis. Results. The hsa-miR-148a-3p expression levels, time from onset of RRD to vitrectomy, range of RD, and pixels of retinal breaks were 23.68 ± 43.00, 12.07 ± 15.36 days, 155.85 ± 86.67 degrees, and 37000 ± 67100 pixels, respectively. Five eyes with RRD had vitreous hemorrhage preoperatively. The hsa-miR-148a-3p expression levels were significantly associated with pixels of retinal breaks ( β = 0.699) and the time from onset of RRD to vitrectomy ( β = 0.358) but not with the range of RD or presence of vitreous hemorrhage. Conclusion. The hsa-miR-148a-3p expression levels in the vitreous fluid were significantly associated with the size of retinal break and disease duration., Competing Interests: The authors declare that they have no competing interests.

Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

To evaluate, using pupillography, the difference between eyes affected by age-related macular degeneration and their contralateral normal eyes with regard to the mean relative afferent pupillary defect (RAPD) score. Also, to ascertain any correlations between this difference in RAPD score and differences in visual acuity or age-related macular degeneration (AMD) dimensions. Measurements were made using the RAPDx pupillographer (Konan Medical, Nishinomiya, Japan), which analyzes pupil response to light stimulation. Both best corrected visual acuity (converted to logMAR) and greatest linear dimension (GLD; calculated on the basis of fluorescence angiography images) were measured. The correlations between RAPD difference and logMAR difference, and GLD difference were then analyzed. The study included 32 patients (18 men, 14 women; mean age = 74.8 ± 9.7 years) who had AMD in 1 eye and a normal fundus in the contralateral eye. Mean resting pupil diameter, mean latency onset of constriction, mean velocity of constriction, and recovery were not significantly different in AMD eyes compared with normal eyes. The mean amplitude of constriction was smaller (P = 0.028), and the mean latency of maximum constriction was shorter (P = 0.0013) in AMD eyes than in normal eyes. Regarding RAPD scores, there was a significant correlation between visual acuity difference and RAPD score differences of both amplitude (P < 0.001, r = 0.53) and latency (P = 0.034, r = 0.33). GLD difference was also significantly correlated with differences in both amplitude (P = 0.021, r = 0.36) and latency (P = 0.033, r = 0.33) scores. RAPD outcomes were correlated with visual acuity and AMD dimension. Automated pupillography may be a useful tool in monitoring the progression of AMD and assessing changes in retinal function that result from novel interventions., Competing Interests: The authors report no conflicts of interest.

Purpose: The purpose of this study was to determine microRNA expression in vitreous and subretinal fluid (SRF) samples from patients with retinal detachment (RD). The pathological importance of the identified microRNA transcript levels was analyzed in vitro., Methods: Vitreous fluid was collected from 10 patients with macular hole (MH), vitreomacular traction syndrome (VMTS), or foveoschisis and from 11 patients with RD. Subretinal fluid was collected from 7 patients with RD. Of these, blood serum was collected in 4 patients. MicroRNA microarray profiling was performed to identify microRNA transcripts that were present in vitreous fluid, and more redundantly detected in SRF, of patients with RD, but not detected in control eyes. Western blotting and scratch assays were performed in ARPE-19 cells and primary human RPE cell lines transfected with microRNA to elucidate the effect of identified microRNA transcripts on epithelial-mesenchymal transition (EMT)., Results: MicroRNA microarray profiling revealed that hsa-miR-148a-3p was the most redundantly detected transcript in SRF and vitreous fluid from patients with RD, but not those with the other diseases. Expression levels of hsa-miR-148a-3p were higher in SRF samples than in blood serum samples in 3 out of 4 patients. Following hsa-miR-148a-3p mimic transfection, ARPE-19 and human RPE cells demonstrated increased expression of α-smooth muscle actin by Western blotting and increased migration ability during scratch assays., Conclusions: The results of the present study indicate that hsa-miR-148a-3p was specifically detected in RD and promotes EMT in RPE.

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy-lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In the hypothalamus, several reports have implied that ROS mediate physiological effects of insulin. In this study, we investigated the mechanisms of insulin-induced ROS production and the effect of ROS on insulin signal transduction in mouse hypothalamic organotypic cultures. Insulin increased intracellular ROS, which were suppressed by NADPH oxidase inhibitor. H2O2 increased phospho-insulin receptor β (p-IRβ) and phospho-Akt (p-Akt) levels. Insulin-induced increases in p-IRβ and p-Akt levels were attenuated by ROS scavenger or NADPH oxidase inhibitor. Our data suggest that insulin-induced phosphorylation of IRβ and Akt is mediated via ROS which are predominantly produced by NADPH oxidase in mouse hypothalamus., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.

Background: Echocardiographic parameters to predict pulmonary capillary wedge pressure (PCWP) in mitral regurgitation (MR) are not yet elucidated. We reported that PCWP could be accurately estimated by novel KT index which is defined as log10[left atrial (LA) emptying function (EF)/LA volume]. We examined the usefulness of the KT index as a predictor of PCWP in primary and secondary MR with sinus rhythm and also MR with atrial fibrillation., Methods: LA dimension, strain, volume, EF, and E/e' were measured in moderate to severe MR with sinus rhythm (n=58, age: 67±8 years) and MR with atrial fibrillation (n=24, age: 69±11 years) just before catheterization and in normal subjects (n=26, age: 67±11 years) using speckle tracking echocardiography. MR with sinus rhythm was divided into primary MR (n=27) and secondary MR (n=31). The estimated PCWP (ePCWP) was calculated as 10.8-12.4×KT index., Results: There was a correlation between PCWP and LA dimension, E/e', minimum LA volume index, active LAEF, total LAEF, or LA strain (r=0.32, r=0.31, r=0.55, r=-0.61, r=-0.51, and r=-0.50, respectively, p<0.05). The better correlation was found between PCWP and ePCWP in MR including both primary and secondary MR and also MR with atrial fibrillation (r=0.70, r=0.67, and r=0.58, respectively, p<0.01). Multiple regression analysis revealed that ePCWP was an independent predictor of PCWP in MR. The ePCWP demonstrated good diagnostic accuracy (area under the curve of 0.86) and sensitivity (81%) and specificity (71%) to predict elevated PCWP >15mmHg using a cut-off of 16mmHg., Conclusion: The ePCWP was the reliable echocardiographic parameter to predict PCWP in primary and secondary MR and might also be useful in MR with atrial fibrillation. The ePCWP may have an incremental value in a clinical setting., (Copyright © 2015. Published by Elsevier Ltd.)

Purpose . It is a matter of increasing concern that exposure to light-emitting diodes (LED), particularly blue light (BL), damages retinal cells. This study aimed to investigate the retinal pigment epithelium (RPE) damage caused by BL and to elucidate the role of nuclear factor (erythroid-derived)-related factor 2 (Nrf2) in the pathogenesis of BL-induced RPE damage. Methods . ARPE-19, a human RPE cell line, and mouse primary RPE cells from wild-type and Nrf2 knockout ( Nrf2 -/- ) mice were cultured under blue LED exposure (intermediate wavelength, 450 nm). Cell death rate and reactive oxygen species (ROS) generation were measured. TUNEL staining was performed to detect apoptosis. Real-time polymerase chain reaction was performed on NRF2 mRNA, and western blotting was performed to detect Nrf2 proteins in the nucleus or cytoplasm of RPE cells. Results . BL exposure increased cell death rate and ROS generation in ARPE-19 cells in a time-dependent manner; cell death was caused by apoptosis. Moreover, BL exposure induced NRF2 mRNA upregulation and Nrf2 nuclear translocation in RPE. Cell death rate was significantly higher in RPE cells from Nrf2 -/- mice than from wild-type mice. Conclusions . The Nrf2 pathway plays an important role in protecting RPE cells against BL-induced oxidative stress.

Minocycline, a derivative of tetracycline, is a broad-spectrum antibiotic used in the treatment of various infections. Black discolouration of the skin, teeth, bones and the thyroid gland are sequelae of long-term minocycline therapy. We report an unusual case of minocycline-induced pigmentation of the aortic valve and sinuses of Valsalva., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Mitogen-activated protein kinase phosphatase 1 (MKP-1) is shown to negatively regulate MAPK signaling in various peripheral tissues as well as the central nervous system such as cortex, striatum and hippocampus. In this study, we examined whether MKP-1 regulates MAPK signaling in the mouse hypothalamus. Intraperitoneal injection of TNFα significantly increased MKP-1 mRNA expression in paraventricular and arcuate nuclei in the hypothalamus. TNFα treatment induced increases in MKP-1 expression at both mRNA and protein levels, accompanied by the inactivation of MAPK signaling in mouse hypothalamic explants. Inhibition of MKP-1 by its inhibitor or siRNA increased MAPK activity in the explants. Our data indicate that MKP-1 negatively regulates MAPK signaling in the mouse hypothalamus., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Bioabsorbable poly-L-lactide (PLLA) sternal pins are applied to reinforce sternal closure during cardiac surgery. However, these pins lack osteoconductivity. A new bioabsorbable sternal pin with osteoconductivity, made of uncalcined hydroxyapatite and poly-L-lactide (u-HA-PLLA) has been developed. This study was conducted to compare the two types of sternal pins in terms of sternal stability and healing after median sternotomy. Between October 2006 and January 2012, 105 patients underwent aortic surgery for aortic aneurysms or dissection via median sternotomy and sternal closure with sternal pins. Among these patients, 75 were followed for 12 months using serial computed tomography (CT). PLLA sternal pins were used in 30 patients (group A) and u-HA-PLLA sternal pins were used in 45 patients (group B). The incidence rates of transverse sternal dehiscence, anteroposterior displacement and complete sternal fusion were evaluated using CT. The cross-sectional cortical bone density area (CBDA) of the sternum around the sternal pins was examined to evaluate the osteoconductivity of the sternal pins. There were no significant differences between groups A and B in the sternal dehiscence rate (6.7 vs 4.4 %), sternal displacement rate (6.7 vs 2.2 %) or 12-month sternal fusion rate (63.3 vs 73.3 %). The CBDA around the sternal pins significantly increased between discharge and 12 months after surgery in group B (P < 0.001) but not in group A. These results show that u-HA-PLLA sternal pins exhibit certain osteoconductivity; however, both PLLA and u-HA-PLLA sternal pins provide comparable clinical outcomes regarding sternal stability and healing.

Although various formulas predicting plasma sodium level ([Na]) are proposed for correction of hyponatremia, it seems that an anticipated [Na] frequently exceeds or falls below the measured [Na], especially in syndrome of inappropriate antidiuretic hormone secretion (SIADH). The causative factors of the fluctuation have never been investigated clearly. The aim of this study was to identify the determining factors for accurate prediction of [Na] by comparing data from previously proposed formulas and a novel osmotic compartment model (O-C model). The O-C model, which simulates the amounts of osmoles in extracellular and intracellular fluids, can estimate resultant osmotic water shift (OWS) and [Na]. The accuracy of representative formulas was verified in a point-to-point study using blood and urine samples obtained every 4 hours from 9 patients. Among 161 measurement points, a large fluctuation of urine volume and urine sodium level was observed. The gap between anticipated and measured [Na] in the widely used Adrogue-Madias formula was -0.5 ± 0.1 mEq/L/4 h (mean ± standard error), showing a marked tendency to underestimate [Na]. The gap in the O-C model including OWS was 0.1 ± 0.1 mEq/L/4 h, and that in the O-C model eliminating OWS was 1.9 ± 0.2 mEq/L/4 h, indicating that measurement of urine output and estimation of resulting OWS are essential for a superior prediction of [Na] in SIADH. A simulation study with the O-C model including OWS unveiled a distinctive correction pattern of [Na] dependent on the urine volume and urine sodium level, providing a useful choice for the proper type and rate of infusion., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Giant bilateral atria with mitral and tricuspid regurgitation can cause postoperative respiratory dysfunction. In this article, we describe a case of giant atria with poor respiratory function that was improved by atrial volume reduction. A 79-year-old woman was referred to our institution for valve surgery. Her vital capacity was 1,080 mL. The mitral and tricuspid valves were repaired during surgery. We removed a circular section of the left atrial wall. The right atrial wall and interatrial septum were removed; this improved her vital capacity to 1,370 mL. We conclude that aggressive volume reduction of both atria improves respiratory function., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A wide and redundant prolapse of the posterior mitral leaflet in active infective endocarditis cannot be easily repaired. A sliding plasty can be attempted, but the range of annular plication is often too large. Chordal replacement is another option, but is prone to long-term degeneration because the redundant leaflet still exists. Here, we describe a simple resection technique that utilizes only two small triangular resections. The resections are sutured with no need to shorten the annulus. The leaflet tissue between the two triangular resections must be preserved to make an appropriately shaped posterior leaflet.

Objectives: We examined the impact of the bioresorbable osteosynthesis sternal pin (Super Fixsorb 30) on sternal healing after median sternotomy., Methods: Sixty-three patients who underwent aortic surgery through median sternotomy between January 2006 and March 2009 were analysed. Sternal pins were utilized in 36 patients in addition to the standard closure of the sternum with Ethibond sutures (Group A), and 27 patients received no pins with the standard Ethibond sternal closure (Group B). The occurrence of transverse sternal dehiscence, anterior-posterior displacement and complete fusion of the sternum were evaluated by a computed tomography scan. The cross-sectional cortical bone density area (CBDA) of the sternum was examined to evaluate the osteoconductivity of the sternal pin over a 12-month period., Results: There was no sternal displacement (0%) observed in Group A at discharge. Meanwhile, five displacements (18.5%) were observed in Group B (P = 0.007). The complete sternal fusion rates at 12 months postoperatively were 100% in Group A, and 21.6% in Group B (P < 0.001). A significant increase in the CBDA was observed in Group A (P < 0.001; between CBDA at discharge and 12 months postoperatively)., Conclusions: The Super Fixsorb 30 sternal pin reduced an anterior-posterior sternal displacement and facilitated an earlier sternal fusion. The pin may have the potential to promote osteogenesis.

A 58-year-old woman was referred to our hospital because of liver dysfunction. Her serum levels of AST (619 IU/l) and ALT (603 IU/l) had increased. Histological findings in the liver biopsy were compatible to autoimmune hepatitis (AIH), and the diagnosis of AIH was confirmed by the diagnostic criteria. She was admitted to a nearby hospital 3 years ago, and diagnosed with Graves' disease. She received methimazole (MMI) at first, which was discontinued due to liver injury in one month, then propylthiouracil (PTU) was administered. One year later, transaminase increased and was decreased by stopping PTU administration. PTU was restarted after her transaminase decreased, but a recurrence of hepatotoxicity was observed, and she was referred to our hospital. Oral prednisolone decreased liver function immediately. In this case, PTU-induced liver injury was suspected as a possible trigger of AIH. While PTU remains a commonly used drug in the treatment of hyperthyroidism, severe liver injury is reported in some cases. If liver injury is observed in patients treated with PTU, rechallenge is not recommended in order to avoid severe hepatotoxicity.

Background: Atherosclerosis-related diseases are leading causes of morbidity among patients undergoing hemodialysis. The effects of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) on the endothelial function of hemodialyzed patients are not known., Methods and Results: For 16 weeks, we prescribed simvastatin (low dose: 5 mg or moderate dose: 10 mg) to 28 patients (low dose: n=14, 61.2 ± 8.6 years, moderate dose: n=14, 60.8 ± 10.2 years) and chose 9 patients (61.5 ± 5.2 years) without prescriptions as controls. We compared the effects of statin on lipids, flow-mediated endothelium-dependent and nitroglycerin-induced endothelium-independent dilatation (%FMD, %NTD), and markers of oxidant stress and atherosclerosis. Serum HDL-cholesterol and triglycerides did not change significantly in any of the three groups; however, LDL-cholesterol was decreased at 16 weeks in both simvastatin groups. The %FMD and plasma NOx increased at 1 and 16 weeks in both statin groups, but not in the control group (P<0.01). The %NTD did not change. Oxidized LDL, VCAM-1, and 8-isoprostane decreased significantly after 16 weeks in both statin groups; however, TNF-α and interleukin 6 did not change. In the control group, no significant changes in these parameters were observed. Multiple regression analyses showed that the (short) period of hemodialysis and (young) age are significant factors associated with %FMD improvement., Conclusions: A statin improved impaired endothelial function in the arteries of chronic dialysis patients, in part by enhancing NO bioavailability within one week. Improved endothelial function is in line with the anti-atherosclerotic effects observed in patients undergoing chronic hemodialysis., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Recently, bipolar radiofrequency (RF) ablation has been introduced as a potential option to replace many of the Cox-maze incisions. We compared the surgical outcomes of maze procedures in patients who had undergone cryoablation and RF ablation and mitral valve surgery., Methods: From January 2004 to August 2009, a total of 40 patients underwent the maze procedure and concomitant mitral operation as a 1st operation. Of these, the cryoablation maze procedure (n = 20) and RF ablation procedure (n = 20) were performed in the patients with similar background, although more patients in the RF group had undergone mitral valve repair (n = 15) compared to the cryoablation group (n = 8) [p = 0.025]., Results: The peri-operative data, such as operative duration, cardiopulmonary bypass time, aortic cross-clamp time, postoperative ventilation time, and the duration of intensive care unit (ICU) stay did not show any significant difference between cryoablation group and RF group. Both ablation procedures were similarly effective in restoring sinus rhythm at the early post-operative period (cryoablation: 80%, RF: 70%). Nine patients in the cryoablation group and 13 patients in the RF ablation group required anti-arrhythmic medication., Conclusions: The RF ablation technique is simpler and equally effective in controlling atrial fibrillation compared to the cryoablation for the maze procedure of concomitant mitral valve surgery.

Background: The aim of this study was to evaluate the early and long-term results of a composite valve graft root replacement for various aortic root diseases., Methods: Between 1978 and 2005, 273 patients with various disorders of the aortic root underwent a composite valve graft root replacement. The mean age of the patients was 47.5 +/- 13.2 years. There were 93 patients with Marfan syndrome, 56 aortitis, and 63 type A aortic dissections. Thirty-nine emergency operations and 55 redo operations were included. For the proximal anastomosis, a skirted technique was used in 157 patients. For the coronary reconstruction, Bentall's original inclusion technique was utilized in 36 patients, a direct button technique in 159, and a graft interposition technique in 63. The mean follow-up was 106 months., Results: The in-hospital mortality was 9.5%. An emergency operation emerged as a significant predictor of early death. The actuarial survival rate was 87.0% and 72.9% at 5 and 15 years, respectively. The age at the operation, aortitis, Marfan syndrome, and use of a standard proximal anastomosis emerged as independent determinants of late death. The actuarial reoperation free rate was 96.3% and 89.7% at 5 and 15 years, respectively. In the patients who underwent the skirted technique the incidence of late graft detachment was less frequent than that of the standard technique., Conclusions: A composite valve graft root replacement is a safe and reliable procedure for various aortic root diseases with stable early- and long-term results. The skirted technique seems to be attractive to avoid late graft detachment even in cases with a fragile inflammatory pathology.

We present a case of successful surgical repair for infected mitral valve and left ventricular pseudoaneurysm, which can be fatal complications of mitral annular calcification.

Objective: Radionuclide imaging with fluorodeoxyglucose (FDG) and positron emission tomography (PET) has been proposed for the identification of vascular graft infection; however, its accuracy has not been determined. We performed this prospective study to compare the usefulness of FDG-PET in the assessment of vascular graft infection relative to computed tomography (CT)., Methods: FDG-PET was performed for 33 consecutive patients with a suspected arterial prosthetic graft infection. The PET images were then assessed visually in terms of the density of uptake. In cases with positive uptake, the pattern of accumulation was also defined, such as focal or diffuse uptake. We compared the diagnostic efficiency of PET with contemporaneous CT in detection of infection of the arterial prosthetic graft., Results: On the basis of the surgical, microbiological, and clinical follow-up findings, the aortic grafts were considered infected in 11 patients and not infected in 22 patients. Although the sensitivity of PET (91%) was higher than that of CT (64%), its specificity (64%) was lower than that of CT (86%). When focal uptake was set as the positive criterion in FDG, the specificity and positive predictive value of PET for the diagnosis of aortic graft infection improved significantly to 95% (P < .05 for both)., Conclusions: Although both techniques are useful in evaluation of patients with suspected aortic graft infection, using the characteristic FDG uptake pattern described previously as a diagnostic criterion made the efficacy of FDG superior to that of CT in the diagnostic assessment of patients with suspected aortic graft infection.

Primary tumors of the heart are rare. The majority of these tumors are benign, with myxomas located in the left atrium being the most common form. Almost all malignant tumors are sarcomas and occur preferentially in the right side of the heart. The case of a 73-year-old woman who presented with symptoms of mitral valve stenosis is reported. Echocardiography revealed a left atrial mass that was interpreted as atrial myxoma. At the operation, the tumor which was lobulated and had a smooth surface was arising from posterior wall of left atrium extending into the mitral annulus. Wide surgical excision was possible with left atrial reconstruction and mitral valve replacement. Histological and immunohistochemical studies revealed malignant undifferentiated sarcoma extending to the surface of mitral valve. Postoperative metastatic work-up showed no evidence of dissemination. The patient survived the operation without adjuvant radiation and chemotherapy and has been symptom-free over 1 year. At present, 16 months following the operation, the patient is alive with no evidence of disease.

Background: The remarkable anti-atherosclerotic effects of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor have not been demonstrated in diet induced severe hyperlipidemia in rabbit model., Objective: We have investigated the effect of pitavastatin, a newly developed statin, on atherosclerosis in rabbits., Methods and Results: Oophorectomized female NZW rabbits were fed 0.3% cholesterol chow for 12 weeks with or without pitavastatin (0.1mg/kg per day) (Gp.NK and HCD). The level of serum cholesterol was decreased in Gp.NK compared with Gp.HCD (772.8 +/- 70.2 versus 1056.9 +/- 108.3 mg/d), whereas no significant alterations were observed in triglyceride and HDL-cholesterol. NO dependent response stimulated by acetylcholine and calcium ionophore A23187 and tone related basal NO response induced by N(G)-monomethyl-l-arginine acetate were all improved by pitavastatin treatment. Pitavastatin treatment increased the level of cyclic GMP in the aorta of cholesterol fed rabbits. In the aorta, the expression of eNOS mRNA was significantly up regulated and O(2)(-) production was slightly reduced in Gp.NK animals. Atherosclerotic area was significantly decreased in aortic arch and thoracic aorta from Gp.NK compared with those from Gp.HCD ( 15.1 +/- 5.3 versus 41.9 +/- 10.2%, 3.1 +/- 1.1versus 7.9 +/- 1.2% in Gp.NK and Gp.HCD aortic arch and thoracic aorta). Anti-macrophage staining area, the MMP1 or 2 and the nitrotyrosine positive area were decreased in Gp.NK., Conclusion: Pitavastatin retards the progression of atherosclerosis formation and it improves NO bioavailability by eNOS up-regulation and decrease of O(2)(-).

The effects of in vivo gene transfer of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) genes on severe atherosclerosis were investigated in rabbits. The recombinant adenoviruses, Ad.eNOS and Ad.iNOS, which respectively express eNOS and iNOS, were constructed. Atherosclerosis was induced by a balloon injury followed by a high cholesterol diet for 12 weeks. The rabbits were divided into six groups: Gp cont (no treatment); Gp null (adenovirus sham-infected); Gp eNOS (Ad.eNOS); Gp iNOS (Ad.iNOS); Gp e+i (Ad.eNOS plus Ad.iNOS); and Gp heNOS (a high dose of Ad.eNOS). Examinations were carried out 7 days after gene transfer. Plasma lipid levels were not significantly changed, but transfection with Ad.eNOS (Gp eNOS and Gp heNOS) decreased the tissue cholesterol concentration and regressed atherosclerotic lesions. Vessels treated with Ad.iNOS (Gp iNOS and Gp e+i) showed iNOS staining in the atheroma, and slight staining at other parts of the vessels; those treated with Ad.eNOS showed eNOS staining in the endothelium and subintima, and slight staining at other parts. Ad.eNOS transfection, but not Ad.iNOS or Ad.eNOS+Ad.iNOS transfection, improved the impaired aortic endothelium-dependent relaxation (EDR) and basal NO-dependent response, increased tissue cyclic GMP (cGMP), and decreased the release of O2- from vessels. eNOS treatment showed a decreasing tendency in regions with peroxynitrite staining, MMP1 staining, and suspected apoptosis. In conclusion, in vivo gene transfer of eNOS, but not iNOS or eNOS plus iNOS, regressed atherosclerosis. The relations among NO, O2-, and peroxynitrite may be critical, and lipid resorption from the lesions may be responsible for the regression.

Although sarpogrelate HCl is widely used for the prevention of arterial thrombosis, its effect on atherosclerosis is unknown. Accordingly, we here investigated the effects of sarpogrelate HCl on a rabbit model of atherosclerosis. Male rabbits were fed a 0.5% cholesterol diet (HCD) (Gp 1), HCD with vitamin E (Gp 2), HCD with vitamin E and sarpogrelate (Gp 3), or HCD with sarpogrelate alone (Gp 4) for 8 weeks. The atherosclerotic area was decreased by feeding of vitamin E and sarpogrelate (16.9+/-2.0% in Gp 1 vs. 8.2+/-2.0% in Gp 3). Tone-related basal NO release was higher in Gps 3 and 4. Acetylcholine-induced relaxation tended to be improved in Gp 3. The amount of eNOS mRNA was increased in Gp 4, and aortic cyclic GMP concentration showed the same tendency. O(2)(-) release tended to be decreased in Gps 2 and 3. The matrix metalloproteinase-1 (MMP-1)-positive area was decreased, and the percentage ratio of cell numbers of smooth muscle cells/macrophages in the plaque was increased in Gp 3. The results demonstrated that sarpogrelate HCl retards the progression of atherosclerosis in rabbits, and that this effect is enhanced by concomitant administration of vitamin E. Although upregulation of eNOS may play a role as one of the underlying mechanisms, our results suggest that an additional mechanism-possibly involving the antiproliferative effects of sarpogrelate HCl on smooth muscle cells and macrophages-may also play an important role.

Objective: We investigated the effect of glimepiride, a third-generation sulfonylurea hypoglycemic agent, on insulin resistance in elderly patients with type 2 diabetes, in connection with plasma adiponectin and 8-epi-prostagrandin F2alpha (8-epi-PGF2alpha), an oxidative stress marker., Research Design and Methods: A total of 17 elderly patients with type 2 diabetes received 12 weeks of treatment with glimepiride. Homeostasis assessment model of insulin resistance (HOMA-IR), homeostasis assessment model of beta-cell function, HbA(1c), C-peptide in 24-h pooled urine (urine CPR), and plasma concentrations of 8-epi-PGF2alpha, tumor necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor type 1, and adiponectin were measured at various times. The metabolic clearance rate of glucose (MCR-g) was also assessed by a hyperinsulinemic-euglycemic clamp., Results: After 8 weeks of glimepiride treatment, significant reductions were observed in HbA(1c) (from 8.4 +/- 1.9 to 6.9 +/- 1.0%), HOMA-IR (from 2.54 +/- 2.25 to 1.69 +/- 0.95%), and plasma TNF-alpha concentrations (from 4.0 +/- 2.0 to 2.6 +/- 2.5 pg/ml). MCR-g was significantly increased from 3.92 +/- 1.09 to 5.73 +/- 1.47 mg. kg(-1). min(-1). Plasma adiponectin increased from 6.61 +/- 3.06 to 10.2 +/- 7.14 micro g/ml. In control subjects, who maintained conventional treatment, no significant changes were observed in any of these markers., Conclusions: Glimepiride remarkably improved insulin resistance, suggested by a significant reduction in HOMA-IR, an increase in MCR-g, and a reduction in HbA(1c) without changing extrapancreatic beta-cell function and urine CPR. Increased plasma adiponectin and decreased plasma TNF-alpha may underlie the improvement of insulin resistance with glimepiride.

Estriol (E3) has little effect on the female genitals. E3 is used in hormone replacement therapy, particularly in Europe and Japan, since it obviates the need for progestin administration. However, the effect of E3 on atherosclerosis has not been elucidated. In this study, we evaluated the effect of E3 on the progression of atherosclerosis in a rabbit model. Thirty-six rabbits total were used. Twenty-eight were bilaterally oophorectomized, and 8 were not. The rabbits were divided into 5 groups and treated for 12 weeks as follows. Gp I (n = 8) was fed a high cholesterol diet (HCD; standard diet plus 0.5% cholesterol); Gp II (n = 8) was fed a HCD with E3 (0.3 mg/kg/day); Gp III (n = 8) was fed a HCD with 17beta estradiol (E2) (0.1 mg/kg/day); Gp IV (n = 8), the non oophorectomized group, was fed a HCD; and Gp NC was oophorectomized (n = 4), and fed a regular diet. E3 treatment increased the plasma E2 and E3 levels in Gp II. The plasma lipid levels were not altered by the E2 or E3 treatment. A HCD diminished the acetylcholine-induced NO mediated relaxation in the thoracic aorta. The E2 treatment (Gp III) and E3 treatment (Gp II) restored the aortic basal NO release and the aortic cyclic GMP levels, particularly effectively in the E3 group. E3 treatment also decreased the atherosclerotic area, and its effect was comparable with E2 (surface involvement: 41.2 +/- 5.1% in Gp I; 10.1 +/- 2.7% in Gp II; and 6.5 +/- 1.3% in Gp III). All four hyperlipidemic groups showed an increase of eNOS mRNA in the aortae, and this was especially pronounced in Gps II and III. The level of peroxynitrite, as determined by immunohistochemical nitrotyrosine staining, was lower in Gps II and III than in Gp I. E3 strongly activates NO-mediated systems, and could play a role in retarding the progression of atherosclerosis and in stabilizing atheroma.

It is not completely understood whether nitric oxide donors and beta-adrenoceptor antagonists have anti-atherosclerotic effects. The anti-atherosclerotic effects of beta-adrenergic receptor antagonists and nitric oxide donors on severe atherosclerosis induced by cholesterol and inhibition of nitric oxide synthesis were determined. Six groups of New Zealand white male rabbits were treated for 10 weeks, under the following regimens: group I: high-cholesterol diet (HCD) (standard diet plus 0.5% cholesterol); group II: HCD plus N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase; group III: HCD plus L-NAME and isosorbide dinitrate; group IV: HCD plus L-NAME and nitroglycerin; group V: HCD plus L-NAME and nipradilol (beta-blocker with nitric oxide-releasing action); and group VI: HCD plus L-NAME and atenolol (beta-blocker). Serum lipid levels did not differ among the six groups. Blood pressure and heart rates were slightly decreased in groups V and VI. The atherosclerotic area and aortic cholesterol increased in L-NAME-treated animals but not in animals in group V. The endothelium-dependent relaxations and basal nitric oxide release were impaired in the L-NAME treatment group, though not in group V, in comparison with those in group I. cGMP in the aorta was increased in groups III, IV, and V as compared with that in group II. Endothelial nitric oxide synthase mRNA was decreased in the aortae of L-NAME-treated rabbits and increased in aortae in group V, in comparison with that in group I. Conclusively, nipradilol, beta-blocker with nitric oxide-releasing action, in contrast to the other beta-blockers and nitric oxide donors, showed a successful anti-atherosclerotic effect through the restoration of nitric oxide bioavailability and possible interaction with oxygen radicals.

Male rabbits fed a 0.5% cholesterol diet for 8 wk were divided into three groups. Group 1 was hypercholesterolemic; group 2 was fed a regular diet for an additional 12 wk; and group 3 was fed a regular diet with simvastatin (5 mg x kg(-1) x day(-1)). Simvastatin treatment reduced the atherosclerotic area and total and esterified cholesterol concentrations in the thoracic aorta. Tone-related basal nitric oxide (NO) release was highest in group 3. Acetylcholine-induced, NO-dependent relaxation was improved in group 3 compared with group 2. Amount of endothelial nitric oxide synthase (eNOS) mRNA in vessels increased in group 1, compared with normal aorta, and decreased in group 2; however, it did not decrease in group 3. The amount of O released from vessels increased in group 1 and group 2 compared with normal rabbits; however, it decreased in group 3, especially in the endothelial cells. Peroxynitrite determined by nitrotyrosine staining decreased in group 3. Additionally, the arteries of rabbits fed a regular diet with or without simvastatin were investigated. The aorta from simvastatin-treated group showed increase of tone-related basal NO release and eNOS mRNA and decrease of O release. Taken together, upregulation of eNOS and decrease of O treatment were observed in vivo in the process of the sufficient stabilization of atheroma following simvastatin.

In order to study the correlation between chronic prostatitis and C. trachomatis, IgA and IgG antibody titers for C. trachomatis were measured in serum and prostatic secretion of cases of chronic prostatitis. IgA antibody titers have higher tendency in prostatic secretion than in serum. The other side, IgG antibody titers have higher tendency in serum than in prostatic secretion. This result suggested IgA antigen was reacted in local immunological response in prostatic gland. Subsequently, in order to confirm that IgA antibody in prostatic secretion is formed from secretory IgA antibody mainly, IgA antibody titers were compared with secretory IgA antibody titers. That results was considered that many cases with high IgA titers had high secretory IgA titers. The fact suggested in cases of C. trachomatis prostatitis, IgA antibody was mainly formed from secretory IgA antibody in prostatic secretion.

The distribution of serotypes of Chlamydia trachomatis in urogenital infection in Sapporo was studied by typing 30 isolates with Monoclonal antibodies and by testing patient sera from 134 individuals with the micro-immunofluorescence test. 1. Among 30 isolates, the majority of strains were identified to be types D and E (23%), followed by G (13%), F (10%), H (10%), I (7%) J (7%) and K (7%) in this order. 2. In 134 patients sera, the most frequent antibody types were B/ED (64.8%), followed by C/J (13.3%), G/F (7.8%), H/I/J (7.1%) and K (2.3%). Thus, serovar D and E were the same predominant type of Chlamydia trachomatis in urogenital infection in Sapporo, as in the USA and Europe.

The study of human papillomavirus (HPV) in the genitalia of all normal males is difficult, therefore cases of chronic prostatitis, a common disease treated in urological clinics, were chosen to identify HPV DNA by using Vira Type (Life Technologies Inc.). Smears of glans and sulcus coronalius of 177 subjects, showed a HPV positive rate of 3.4%, while 86 cases of those cases were negative for HPV in urethral smears. The lack of clinical findings suggests that HPV is an asymptomatic infection. In a follow up examination of 5 HPV positive cases some weeks later, smears of glans, sulcus coronalius and urethra were all negative for HPV. Examination by Vira Type showed that HPV disappeared spontaneously in these cases.

The efficacy of single administration of NY-198 in the treatment of gonococcal infections was studied employing male patients with gonorrheal urethritis and female patients with gonorrheal cervicitis. The clinical efficacy was evaluated on the basis of the efficacy rates which was estimated on each observation day for each patient. In the male patients, NY-198 was administered in a dose of 200 mg in 25 cases and a dose of 400 mg in 65 cases. The rate of eradication of N. gonorrhoeae (i.e. efficacy) on the 3rd day of administration was 96% in the 200 mg administration group and 100% in the 400 mg administration group. On the 7th day after administration, the eradication rate was 100% in both the 200 mg and 400 mg administration groups. When the eradication rate on the 7th day was statistically estimated for patients who returned to the hospital only on the 3rd day, it was 97.9% in the 200 mg administration group. In the female patients, NY-198 was administered in a dose of 200 mg to 4 cases and a dose of 400 mg to 5 cases. The eradication rate on each observation day was 100% in both dosage groups. In conclusion, single administration of NY-198 in a dose of 200 mg or 400 mg was highly effective, and considered to be a therapeutic method highly useful clinically.

Chlamydia trachomatis infection in the general population has recently been attracting attention. In this regard, we examined the incidence of positive antigen in the genital organs in pregnant female women in order to investigate the prevalence of this infection. EIA (Chlamydiazyme) was performed in 5,000 married pregnant women, and in 317 unmarried women who underwent artificial termination of pregnancy. The study was carried out between June 1986 and September 1989 in Sapporo City (3,932 subjects), Kushiro City (328 subjects), Muroran City (280 subjects), Kitami City (357 subjects), Kucchan Town (220 subjects) and Urakawa Town (200 subjects). 1. Among married pregnant women, the detection rate of C. trachomatis was 6.1% (222/3,666) in Sapporo City, 7.3% (24/328) in Kushiro City, 6.1% (17/280) in Muroran City, 7.8% (24/306) in Kitami City, 6.8% (15/220) in Kucchan Town and 7.5% (15/200) in Urakawa Town, showing no particular difference according to the area. The overall detection rate was 6.3% (317/5,000). 2. The rates of detection of C. trachomatis antigen by EIA were 22.9% (61/266) and 15.7% (8/15) for the unmarried women who underwent artificial termination of pregnancy in Sapporo and Kitami, respectively. Both rates were higher than those in the married pregnant women. This result suggests the prevalence of C. trachomatis among young women showing a high level of sexual activity. 3. Among married subjects, the detection rate was 21.3% for those in their late teens, 8.9% for those in their early 20s, 6.0% for those in their late 20s, 3.7% for those in their early 30s, and 2.9% for those 35 years or older; thus, the younger they were, the detection rate became elevated. The above findings show that latent epidemics of C. trachomatis infection are present to a considerable extent among young women.

We surveyed Chlamydial infection with Chlamydiazyme for 3010 pregnant housewives in Hokkaido. Four hundred and fourty six out of the 3010 pregnant housewives were also be retrospectively investigated for the influence of C. trachomatis on outcome of pregnancy and on their newborns. The results were as follows. 1) Of the 3010 pregnant housewives, 217 (7.2%) were C. trachomatis-antigen positive, when their endocervical specimens were tested. There was no difference in the positive rate of C. trachomatis among the six cities where our investigation was performed. 2) A high C. trachomatis-positive rate (21.9%) was achieved in the pregnant teen-aged housewives with a significant decrease as age increased. 3) As for placenta previa, threatened abortion, preterm delivery and small for date infants, the incidence was higher in the untreated C. trachomatis positive group than in the C. trachomatis negative group. 4) The weeks of gestation and birth weight of newborns in the untreated C. trachomatis positive group were significantly lower than those of the C. trachomatis negative group. 5) No statistical significance was found in the incidence of premature rupture of membrane, fatal distress, spontaneous abortion nor postpartum fever between the C. trachomatis negative group and the untreated C. trachomatis positive group. These results suggest that Chlamydial infection in pregnant housewives is widely spread in Hokkaido and gives some disadvantage to pregnancy outcome and newborns. Consequently, Chlamydial infection in pregnant women must be appropriately diagnosed and treated in the early stage of pregnancy.

Efficacy and safety of ofloxacin (OFLX), a new quinolone antibacterial agent, were investigated in cases of sexually transmitted male urethritis and cervicitis. Chlamydial infections occupied a large part of the patients enrolled. This study was conducted in 29 institutions. A total of 1,126 patients with gonococcal, chlamydial or non-gonococcal non-chlamydial infections were enrolled in the study. The general dosing regimen of oral OFLX was 100 mg t.i.d. or 200 mg t.i.d. for 14 consecutive days. Along with the clinical efficacy evaluated by doctors in charge, therapeutic and clinical efficacies were determined according to standardized evaluation criteria. The evaluation of therapeutic efficacy was based on bacterial eradication. On the other hand, clinical efficacy was determined upon the improvement in causative bacteria, WBC counts in smear (or initial urine) specimens and urethra/cervical discharges. Clinical efficacy was determined on 7 and 14 days after starting the medication, except for gonococcal infections for which the efficacy was determined on Day 3 and Day 7. The results obtained are summarized as follows. 1. Efficacy evaluation by standardized criteria Therapeutic efficacy rates in gonococcal infections were 97.9% (93/95) on Day 3 and 100% (119/119) on Day 7. In chlamydial infections, the rates were 77.7% (363/467) on Day 7 and 93.6% (392/419) on Day 14. Chlamydial urethritis rated 94.8% (239/252) and cervicitis 91.6% (153/167) on Day 14. Clinical efficacy rates in gonococcal infections were 63.2% (60/95) on Day 3 and 95.8% (114/119) on Day 7. In chlamydial infections, they were 70.0% (327/467) on Day 7 and 89.7% (376/419) on Day 14. Chlamydial urethritis rated 88.5% (223/252) and cervicitis 91.6% (153/167) on Day 14. Clinical efficacy rates in non-gonococcal non-chlamydial infections were 93.3% (97/104) for male urethritis and 65.9% (27/41) for cervicitis on Day 14. 2. Clinical efficacy determined by doctors in charge A total of 1,028 cases, 752 urethritis and 276 cervicitis cases, was evaluated by doctors in charge. Clinical efficacy rates were 90.3% for urethritis and 92.4% for cervicitis. 3. Safety Safety evaluations was conducted in 1,087 patients. Side effects were observed in 23 patients among them (2.12%). None of them were deemed serious. General laboratory examinations were conducted for 169 patients. Abnormal findings were seen in 11 patients (6.51%) or 13 cases, all of which were minor. The results of this multi-center clinical trial demonstrated that OFLX is effective and well tolerated in the treatment of sexually transmitted disease (STD), both gonococcal and chlamydial infections.