Damage accrual related to pregnancies before and after diagnosis of systemic lupus erythematosus: a cross-sectional and nested case-control analysis from a lupus registry.

OBJECTIVE: The objective of this study was to evaluate the chronic damage associated with pregnancies before and after the diagnosis of systemic lupus erythematosus (SLE). METHODS: Using childbearing-aged female SLE patient data registered at the Okayama and Showa University Hospitals, a nested case-control analysis was performed to investigate the relationship between pregnancy and chronic damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). RESULTS: Pregnancy occurred in 22 patients before and 13 patients after the diagnosis of SLE in 104 eligible patients. Live births occurred in 82% (33/40) and 50% (9/18) of the pregnancies before and after the diagnosis of SLE, respectively. After matching age and disease duration, 33 case patients with chronic damage (SDI ≥ 1) and 33 control patients without chronic damage (SDI = 0) were selected. Hypertension was more frequent in cases than in controls (48% vs. 24%, p = 0.041). Pregnancies before and after the diagnosis of SLE were comparable between cases and controls (before the diagnosis: nine case patients and eight control patients; after the diagnosis: three case patients and five control patients; p = 1.00). Even after adjusting for hypertension using multivariate analysis, the pregnancies before and after the diagnosis were not significant predictors for chronic damage (odds ratio = 1.48 (95% confidence interval 0.33-6.65)), p = 0.60 of the pregnancy before the diagnosis; odds ratio = 0.78 (95% confidence interval 0.13-4.74), p = 0.78 of the pregnancy after the diagnosis). CONCLUSION: Pregnancies, either before or after the diagnosis of SLE, did not show any differences in chronic damage. Our results help alleviate fears regarding childbearing in female patients with SLE and their families.

Progressive reduction of serum complement levels: a risk factor for relapse in patients with hypocomplementemia in systemic lupus erythematosus.

OBJECTIVE: Serologically active clinically quiescent (SACQ)-SLE is a subtype of systemic lupus erythematosus (SLE); most SACQ-SLE patients relapse. Although complement and/or anti-dsDNA level fluctuations during SACQ status are reportedly not useful for predicting relapse, they might be useful in specific clinical settings. We aimed to assess the correlation between future relapse and progressive reductions in serum complement levels following remission in patients with hypocomplementemia . METHODS: We retrospectively reviewed patients aged ≥15 years who were treated with ≥20 mg/day of prednisolone for remission induction. After achieving remission, the patients treated with prednisolone tapered to ≤15 mg/day without relapse and followed by hypocomplementemia (first hypocomplementemia point) were analyzed. The primary outcome was the relapse during the first 24 months. RESULTS: Seventy-six patients were enrolled; 31 (40.8%) relapsed. A ≥10% reduction after the first hypocomplementemia point in serum C3, C4, and CH50 levels was found in 10, 21, and 16 patients, respectively. Hazard ratios (95% confidence intervals) for relapse were 2.32 (0.92-5.12) for serum C3 levels and 2.46 (1.18-5.01) for serum C4 levels. Progressive reductions in serum C3 and C4 levels had relatively high specificity (93.3% and 82.2%) but limited sensitivity (22.6% and 41.9%) for predicting relapse. However, simultaneous progressive reduction in C3 levels and increase in anti-dsDNA antibody levels had the highest specificity (97.8%), and simultaneous progressive reduction in C4 levels or increase in anti-dsDNA antibody levels had the highest sensitivity (71.0%). CONCLUSION: Simultaneous progressive reductions in complement levels and increases in anti-dsDNA antibody levels may indicate future relapse SACQ-SLE patients.

Refractory neuromyelitis optica spectrum disorder in systemic lupus erythematosus successfully treated with rituximab.

We present a case of a woman with systemic lupus erythematosus (SLE) who had refractory episodes of neuromyelitis optica spectrum disorder (NMOSD) and was successfully treated with rituximab. She was positive for anti-aquaporin-4 (AQP4) antibody and had typical cranial and longitudinally extended spinal lesions but no optic nerve involvement. There is no established treatment for NMOSD/SLE overlap cases. Our experience suggests that rituximab may be effective for patients with combined SLE and anti-AQP4 antibody-positive NMOSD.

Head position affects the direction of occlusal force during tapping movement.

Despite numerous reports describing the relationship between head position and mandibular movement in human subjects, the direction and magnitude of force at the occlusal contacts have not been investigated in relation to head position. The objective was to investigate the effect of head position on the direction of occlusal force while subjects performed a tapping movement. Twenty-three healthy adult subjects were asked to sit on a chair with their back upright and to perform 15 tapping movements in five different head positions: natural head position (control); forward; backward; and right and left rolled. The direction and magnitude of force were measured using a small triaxial force sensor. The Wilcoxon signed-rank test and Bonferroni test were used to compare head positions in each angle of the anteroposterior axis direction and the lateral axis direction with respect to the superior axis. The force element in the anteroposterior axis shifted to the forward direction in the head position pitched backward, compared with control, pitched forward and rolled left positions (P = .02, <.01 and <.01, respectively). The force direction in the lateral axis with the head position rolled to the right or left shifted to the left and right directions, respectively, compared with those in the other positions (P < .05). Results of this study suggest that the head should be maintained in a position in which a stable tapping movement can be performed in a relaxed position without anteroposterior and lateral loading.

The efficacy of add-on tacrolimus for minor flare in patients with systemic lupus erythematosus: a retrospective study.

OBJECTIVE: We have assessed the effectiveness of tacrolimus for minor flares in systemic lupus erythematosus (SLE) patients. METHODS: The medical records of 313 patients were retrospectively reviewed over a period of seven years, from 2006 to 2013. We enrolled patients with minor flare treated with add-on tacrolimus, without glucocorticoid (GC) intensification (tacrolimus group). Minor flare was defined as a ≥ 1-point increase in a total score between 3 and 11 in the SLE Disease Activity Index (SLEDAI). We enrolled as controls patients who were administered increased doses of GC for minor flare (GC group). All patients were followed for one year. The primary outcome measure was the proportion of responders. RESULTS: There were 14 eligible patients in the tacrolimus group and 20 eligible patients in the GC group. The mean SLEDAI at flare tended to be higher in the tacrolimus group than in the GC group (7.5 vs. 6.2, p = 0.085). A mean dose of 1.6 mg tacrolimus/day was administered for flare, while the mean GC dose was 13.7 mg/day in the GC group. The proportion of responders was 86% (12/14) in the tacrolimus group and 75% (15/20) in the GC group (p = 0.67). The mean dose of GC at 12 months was higher in the GC group than in the tacrolimus group (9.7 mg/day vs. 7.1 mg/day, p < 0.05). Only one patient discontinued tacrolimus because of fatigue after three months. CONCLUSION: Adding tacrolimus without increasing the GC dose may provide an effective treatment option for minor flares in patients with SLE.

Cognitive and affective functions in diabetic patients associated with diabetes-related factors, white matter abnormality and aging.

BACKGROUND AND PURPOSE: Diabetes mellitus (DM) is associated with a decline in cognitive and affective functions. METHODS: In all, 182 outpatients with DM were investigated for associations of cognitive and affective functions with diabetes-related factors and cerebral white matter abnormalities. In addition, the difference in cognitive decline of age-matched late elderly normal subjects and DM patients was investigated. RESULTS: The present study revealed that cognitive and affective functions declined in some DM patients. Furthermore, the decline in these functions was unrelated to fasting blood sugar level but was related to glycosylated hemoglobin (HbA1c) and insulin resistance. Poor HbA1c control was associated with a significant decline in the 'calculation' subscale and insulin resistance for 'naming', 'read list of letters' and 'delayed recall' Montreal Cognitive Assessment (MoCA) subscale scores. Magnetic resonance imaging scans showed that both periventricular hyperintensity (PVH) and deep white matter hyperintensity were associated with Mini Mental State Examination (MMSE) and MoCA scores, but only PVH was related to homeostasis model assessment of insulin resistance scores. Compared with age-matched late elderly normal subjects, 'orientation to time' and 'registration' MMSE subscales declined in late elderly DM patients. CONCLUSIONS: These results suggest that cognitive and affective decline in DM patients was mostly related to glucose control and insulin resistance, whilst amongst late elderly subjects the impairment of 'attention' and 'orientation' were characteristic features of DM patients.

Comparison of insulin detemir and insulin glargine on glycemic variability in patients with type 1 and type 2 diabetes.

AIMS: To compare the glycemic variability of insulin detemir and insulin glargine in type 1 and type 2 diabetic patients. METHODS: 15 type 1 and 14 type 2 diabetic patients receiving intensive insulin therapy with insulin glargine were enrolled. Before and after switching insulin glargine to insulin detemir, we assessed fasting glucose variability using the standard deviation (SD) and the coefficient of variance (CV) of self-monitored fasting blood sugar (FBS) levels. RESULTS: The SD and CV values were significantly decreased in type 1 diabetes after switching the therapy, though there was no significant difference in type 2 diabetes. The frequency of hypoglycemia was decreased in type 1 diabetes and there was no change in type 2 diabetes. The changes of the CV value also showed significant positive correlation with fasting serum CPR levels in all patients and total insulin dose in type 1 diabetes. The changes of frequency of hypoglycemia showed significant positive correlation with total and basal insulin dose adjusted for body weight in type 1 diabetes. CONCLUSION: The present study demonstrated lower within-subject variability of insulin detemir compared to insulin glargine, suggesting that the basal insulin replacement with insulin detemir may provide a useful therapeutic strategy for uncontrolled type 1 diabetes with high glucose variability.

Two cases of ovarian cancer at an early stage incidentally detected using transvaginal ultrasonography in screening: importance of interval for ovarian cancer screening and selection of population with a high risk of ovarian cancer.

Interval of ovarian cancer screening using transvaginal ultrasonography (TVS) and selection of populations with a high risk of this disease are an important issue in detecting early stage-disease. We report two cases of ovarian cancer patients incidentally detected at FIGO Stage I using TVS in the obligatory staff health check. They had undergone other ovarian cancer screening by TVS six months before and received a carefree result at that time. One patient had risk factors (RFs) for ovarian cancer such as obesity and a familal history of ovarian cancer in a first degree relative, and the other had RFs such as obesity and endometrial malignancy. Although cost-effective screening may be important, we recommend that while normal and asymptomatic populations are screened annually, women with any high RFs for ovarian cancer should be screened every six months.

Neuroendoscopic trans-third ventricle approach for lesions of the ventral brainstem surface.

Due to the establishment in recent years of neuroendoscopic third ventriculostomy (ETV), it has become possible during ETV to observe the ventral brainstem surface--particularly the prepontine cistern--in a minimally invasive manner via the third ventricular base with a neuroendoscope. As an adaptation of that technique in this study, we investigated a neuroendoscopic trans-third ventricle approach (ETTVA), which accesses lesions of the ventral brainstem surface with a neuroendoscope inserted via the stoma of the third ventricular floor. Our study included 6 cases, including one case each of neurenteric cyst, chordoma, pontine glioma (astrocytoma), ecchordosis physaliphora, endodermal cyst, and cystic schwannoma. Surgical operations performed by ETTVA included 3 cases of tumor resection, 2 cases of tumor biopsy, and 1 case of cyst puncture and aspiration. There were no complications accompanying ETTVA. Out of the 6 cases, only 1 required additional surgical treatment following ETTVA surgery. In the other 5 cases, no additional surgical procedures were performed. This study showed that ETTVA allowed access to the prepontine cistern quickly and in a minimally invasive manner. In selected cases, ETTVA can offer a new approach to these lesions.

Depression among caregivers of the frail elderly in Japan before and after the introduction of the Public Long-Term Care Insurance System.

Cross sectional studies were conducted in five towns in Japan before and after the introduction of the Long-term Care Insurance System (LTCIS), in order to evaluate the factors relating to depression among family caregivers for the frail elderly. Depressive caregivers were more likely to consult with their doctors, to be in poor health, to care for demented elderly with behavioral disturbances than the non-depressive caregivers both before and after the LTCIS. Before LTCIS, depressive caregivers were more likely to attend to the elderly for more than 16 hours per day than their counterparts. After the LTCIS, depressive caregivers were more likely to be a spouse, to care for a frail elderly male, and less likely to be able to go out without accompanying the elderly than their counterparts. Even after the introduction of LTCIS, half of the caregivers were depressive. It is suggested that a government agency should be created to support not only the frail elderly but also their caregivers.

Patient specific simulation and navigation of ventriculoscopic interventions.

In this paper a comprehensive framework for pre-operative planning, procedural skill training, and intraoperative navigation is presented. The goal of this system is to integrate surgical simulation with surgical planning in order to improve the individual treatment of patients. Various surgical approaches and new, more complex procedures can be assessed using a safe and objective platform that will allow the physicians to explore and discuss possible risks and benefits prior to the intervention. A simulation environment extends the pre-operative planning in a natural way, as it allows for direct evaluation of the surgical approach envisioned for each case. In addition, by providing intraoperative navigation based on this simulation, surgeons can carry out the previously optimized plan with higher precision and greater confidence.

Erythromycin ameliorates renal injury via anti-inflammatory effects in experimental diabetic rats.

AIMS/HYPOTHESIS: Recent studies have shown that the inflammatory process is involved in the pathogenesis of diabetic nephropathy. Fourteen-membered ring macrolides, including erythromycin, have anti-inflammatory, as well as antibacterial effects. The aim of this study was to investigate the renoprotective effects of erythromycin in streptozotocin (STZ)-induced diabetic rats. METHODS: STZ-induced diabetic rats were treated orally with erythromycin (5 mg/kg body weight) or vehicle every day for 8 weeks. To evaluate the effect of erythromycin treatment, we measured urinary albumin excretion, and examined the following in the kidney: histological changes, the expression of intercellular adhesion molecule-1 (ICAM-1), macrophage infiltration, and nuclear factor-kappa B (NF-kappaB) activity. RESULTS: Erythromycin significantly reduced urinary albumin excretion without affecting blood glucose levels and blood pressure. Erythromycin also attenuated glomerular hypertrophy, mesangial expansion, macrophage infiltration and ICAM-1 expression in renal tissues. The expression of the gene encoding TGFB1 (also known as TGF-beta1), type IV collagen protein production and NF-kappaB activity in renal tissues were increased in diabetic rats and reduced by erythromycin treatment. CONCLUSIONS/INTERPRETATION: Erythromycin prevented renal injuries without changes of blood glucose levels and blood pressure in experimental diabetic rats. These results suggest that the renoprotective effects of erythromycin are based on its anti-inflammatory effect via suppression of NF-kappaB activation. Modulation of microinflammation with erythromycin may provide a new approach for diabetic nephropathy.

Indications for neuroendoscopic aqueductoplasty without stenting for obstructive hydrocephalus due to aqueductal stenosis.

OBJECTIVE: Neuroendoscopic aqueductoplasty (EAP) is a curative and radical procedure for obstructive hydrocephalus due to aqueductal stenosis that re-establishes the physiological circulation of cerebrospinal fluid (CSF). We assessed the indications for safe neuroendoscopic aqueductoplasty without stenting to treat aqueductal stenosis. METHODS: In the past 5 years, 6 (5.5 %) of the 110 patients with obstructive hydrocephalus due to aqueductal stenosis were judged to be suitable for EAP on the basis of the MRI features of the aqueduct and intraoperative neuroendoscopic findings from the third ventricle for the aqueductal stenosis. The remaining 104 patients were treated by neuroendoscopic third ventriculostomy. Indications for safe EAP were determined retrospectively based on the clinical features, preoperative MRI, intraoperative neuroendoscopic findings and outcome of the 6 patients who underwent EAP. RESULTS: There were no deaths due to EAP. All of the patients showed improvement or resolution of their preoperative symptoms. In 5 patients, dilatation of the third ventricle and lateral ventricles diminished, and prestenotic dilatation of the aqueduct also disappeared. After an average follow-up period of 39.5 months, recurrence of aqueductal stenosis has not been observed. In one patient, there was a complication of oculomotor nerve paresis after EAP. CONCLUSIONS: EAP can be considered the best surgical procedure for restoring physiological circulation of CSF in patients with obstructive hydrocephalus caused by aqueductal stenosis. However, EAP candidates must be selected very carefully using the following indications: 1) obstructive triventricular hydrocephalus with increased intracranial pressure, 2) translucent membranous stenosis or aqueduct obstruction, and 3) prestenotic dilatation of the aqueduct.

Distribution of estrogen, nonylphenol and its derivatives in the sediments of a shallow lake.

To determine the distribution of endocrine disruptors (EDs) in lake water and sediments, field investigation was conducted in Lake Teganuma, which is a shallow eutrophic lake, highly affected by human activities. Concentration profiles with sediment depths were obtained for estrogens, nonylphenol (NP), nonylphenol ethoxylates (NPnEO), and nonylphenoxy acetic acids (NPnEC). 17beta-Estradiol (E2) was rarely detected, and 17alpha-ethynylestradiol (EE2) and estriol (E3) were undetected at all depths (0-98 cm) in any of the sediment core samples. The sediment concentrations of estrone (E1) ranging from <0.05 to 3.5 microg/kg-dry wt. and NP from 11.8 microg/kg-dry wt. to 21 mg/kg-dry wt. were obtained. The maximum concentrations of NPnEO and NPnEC in the core sediments were 2.5 mg/kg-dry wt. and 1.4 mg/kg-dry wt., respectively. The EDs concentrations are higher at the inlet than at the outlet (except for NP) in the sediments near the surface. The longitudinal distributions of E1, NPnEO and NPnEC in the benthic sediments show that the concentrations are highest at the inlet, and are fairly constant at lower levels towards the downstream. The obtained results also indicate that NP tends to be adsorbed to the organic particulates produced by algae, followed by sedimentation near the outlet of the lake.

Changes in serum leptin concentrations in overweight Japanese men after exercise.

AIM: To investigate the link between serum leptin concentrations and exercise. DESIGN: Cross-sectional and longitudinal studies of an exercise intervention. SUBJECTS: 110 Japanese overweight men aged 32-59 years were recruited. At baseline, the average body mass index (BMI) was 28.5 +/- 2.5 kg/m2. From this group, we used data of 36 overweight men (BMI, 28.9 +/- 2.3) for a 1-year exercise programme. MEASUREMENTS: Leptin was measured at baseline and after 1 year. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical levels. Anthropometric parameters, aerobic exercise level, muscle strength and flexibility were also investigated at baseline and after 1 year. RESULTS: In the first analysis, using cross-sectional data, leptin was significantly correlated with total body fat (r = 0.760, p < 0.01), V (r = 0.383, p < 0.01) and S (r = 0.617, p < 0.01) areas. In the second analysis, using longitudinal data, leptin was significantly reduced after 1 year (pre 6.7 +/- 4.0 ng/ml vs. post 5.1 +/- 3.1 ng/ml, p < 0.01). Results showed that steps per day were increased, and aerobic exercise level, weight-bearing index (WBI) and insulin resistance were significantly improved. Although, there was a positive correlation between Delta leptin(positive changes in leptin after 1 year) and anthropometric measurements such as Delta body weight, Delta BMI and Delta body fat, leptin/body weight, leptin/BMI and leptin/body fat ratios were significantly reduced during exercise intervention. CONCLUSION: The present study indicated exercise significantly lowers serum leptin concentrations, and thus it may improve the leptin resistance observed in overweight Japanese men.

Endoscopic transmaxillary reduction and balloon technique for blowout fractures of the orbital floor.

The indications for and timing of surgical treatment of blowout fractures of the orbital floor remain controversial. We report good results with the endoscopic transmaxillary reduction and balloon technique for blowout fractures of the orbital floor in the early stage after trauma in a consecutive series of 29 patients treated over the last 3 years, based on the following criteria: 1) diplopia observed by ophthalmological examination, 2) entrapment of intraorbital tissue at the fracture site on diagnostic imaging, mainly using CT scans, and 3) no improvement of diplopia during the acute phase (within one week of injury). Even in the presence of eyelid swelling, this method allows reduction and fixation of the fracture and impacted tissues simply and in a short time. Disappearance of diplopia was reported by 27 patients (93 %) within three months after surgery, and all 20 patients with enophthalmos were cured. There were only 4 cases with transient minor operative complications. Re-entrapment at the fracture site or relapse of symptoms was not seen during follow-up for 5 to 39 months (mean: 23.4 months). The combination of endoscopic transmaxillary reduction and the balloon technique for blowout fractures of the orbital floor is an effective and minimally invasive treatment with a high rate of improvement, not just for disturbances of ocular movement, but also for enophthalmos, which is often a problem in the long term.

Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education.

OBJECTIVE: To investigate whether the changes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and after weight reduction in Japanese overweight men are associated with changes in body mass index (BMI), visceral, subcutaneous fat, VO(2) and work rate (WR) at ventilatory threshold (VT). DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: In total, 30 Japanese overweight men (BMI, 29.0+/-2.2 kg/m(2)) and 31 normal-weight men (BMI, 22.5+/-1.6 kg/m(2)) at baseline were enrolled: 30 overweight men (BMI, 29.0+/-2.2 kg/m(2)) were further enrolled into a 6-month exercise program. MEASUREMENTS: Fat distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, angiogenic peptides including VEGF and bFGF, exercise tests at baseline and after 6 months. RESULTS: In normal-weight and overweight subjects at baseline, VEGF positively correlated with S area (r=0.350, P=0.007) but not with V area. In contrast, bFGF negatively correlated with BMI (r=-0.619, P<0.001), S (r=-0.457, P<0.001) and V areas (r=-0.466, P<0.001). By intervention with exercise education, 30 overweight subjects showed reduction in BMI (29.0+/-2.2 to 28.0+/-2.0, P<0.001), V and S areas, increase in VO(2) and WR at VT, increase in bFGF (9.21+/-5.82-21.2+/-7.04 ng/ml, P<0.001), and no change in VEGF (1.45+/-0.72-1.88+/-0.52 ng/ml, P=0.016). The stepwise multiple regression analysis revealed that DeltaBMI (beta=-6.052) and DeltaVO(2) (beta=2.806) were independently related to DeltabFGF (P<0.001) and all other variables including DeltaS area, and DeltaV area, and DeltaWR did not enter the equation at significant levels. CONCLUSION: The present study indicated a negative correlation between serum bFGF levels and BMI at baseline as well as an association of DeltaBMI and DeltaVO(2) with DeltabFGF after exercise intervention. The exercise-induced elevation of bFGF may be beneficial in the prevention of the atherosclerosis in overweight subjects.

Performance analysis on hybrid ventilation system for residential buildings using a test house.

Hybrid ventilation system is a two-mode system that can automatically switch between passive and mechanical modes at different times of the day or season of the year. In this study various ventilation systems, including hybrid system, are used for the investigation. These systems are set up in a full-scale test house constructed in the Tohoku University, Japan. Case studies for evaluating the performance of these systems, by field studies and numerical simulations, are described. The results obtained from this study show that, the hybrid system can supplement the under-ventilation even under a milder weather condition and the airflow rate can be fixed at a certain high level, in comparison with passive system.