The incidence of lumbar spinal canal stenosis (LSCS) is increasing in Japan. Posterior lumbar decompression surgery, wide fenestration and laminectomy, for LSCS is a common treatment modality. Compared with posterior fusion surgery, posterior decompression surgery has been considered as less invasive. However, no reports regarding postoperative anemia following posterior decompression surgery have been published. In this retrospective study, we evaluated changes in hemoglobin values following wide fenestration in 80 patients with LSCS based on the number of operated levels, and also analyzed the differences between intraoperative and postoperative bleeding volume. Two patients required allogenic transfusion. The mean preoperative hemoglobin values were 13.6 g/dL and the mean postoperative minimum hemoglobin values were 11.2 g/dL. The mean hemoglobin values decreased by 1.8 g/dL in patients with one operated level (n = 15); 2.2 g/dL in those with two operated levels (n = 31); 2.6 g/dL in those with three operated levels (n = 23); and 3 g/dL in those with four operated levels (n = 11). The mean decrease in hemoglobin values was calculated as follows: 1.8 + 0.4 × (X − 1), where X was the number of operated levels. The mean intraoperative bleeding volume was 94 ml and the mean postoperative bleeding volume was 418 ml. Postoperative bleeding volume was significantly larger than intraoperative bleeding volume. Accordingly, postoperative hemoglobin values can be predicted in patients undergoing wide fenestration. Effective management of postoperative bleeding is necessary to prevent postoperative anemia.
Psychosocial stress is generally associated with adverse health behaviors and has been linked to the development of cardiovascular diseases (CVD). Recently, an individual's sense of coherence (SOC), which is a concept that reflects the ability to cope with psychosocial stress, has been recognized as an essential component of long-term health and stress management. The association between SOC and traditional and alternative atherosclerotic markers in a community sample, however, has not been thoroughly investigated. In the present study, we evaluated stress management capability and psychological conditions using the Japanese version of the Sense of Coherence-13 (SOC-13) Scale, supplemented by the General Health Questionnaire-12 (GHQ-12) that screens for minor psychiatric disorders. The study subjects were 511 adults, median age 64 years (range 48-70), who participated in a regular medical screening program in Nagasaki Prefecture, Japan. We then correlated our findings with atherosclerotic risk factors in the same community sample, such as body mass index (BMI) and proper and regular sleeping habits. We found that close association between good stress management capability and lower BMI and/or regular sleeping habits in elderly Japanese. This provides strong evidence that BMI and sleep management are contributory to SOC. If the ability to cope with psychosocial stress is important to the prevention of CVD, then weight control and proper sleep habits must be emphasized from a psychosocial stress-management perspective as well as a physical one.
Regular physical activity is associated with improvements of metabolic syndrome (MetS) risk factors. Furthermore, recent physical activity guidelines for health promotion recommend that moderate to vigorous physical activity should be performed in bouts lasting ≥ 10 min. Brisk walking is a popular and readily attainable form of moderate intensity physical activity and is suitable for the majority of individuals. However, it is unclear whether brisk walking lasting ≥ 10 min is associated with improvement in MetS. This study aimed to determine the effects of a 1-year lifestyle-based physical activity intervention with brisk walking of ≥ 10 min using a pedometer on the improvement in MetS. Three hundred and seventy-six overweight male employees with ≥ 1 MetS component(s) participated in this intervention study from 2008 to 2009 (age, 30-62 years; body mass index, 23.0-45.5 kg/m2). Overall, 316 participants (84%) completed the 1-year intervention. MetS was defined according to the Japanese criteria at baseline and after 1 year. Brisk walking lasting ≥ 10 min was significantly associated with the decrease in waist circumference (β = −1.479) and triglyceride (β = −31.260), and the increase in high-density lipoprotein cholesterol (β = 2.117). The brisk walking step counts were also significantly associated with higher odds for an improvement in MetS (OR, 1.48; 95% CI, 1.05-2.09) and abdominal obesity (OR, 1.45; 95% CI, 1.12-1.87). In conclusion, the lifestyle-based intervention with brisk walking of ≥ 10 min is an effective strategy to improve MetS in overweight male employees.
It has been reported that intermittent administration of human parathyroid hormone (h-PTH) promotes bone healing after surgery for osteoporotic fractures. If bone healing is promoted by the administration of h-PTH during pre-operative waiting period, we can prevent prolonged bed rest. Therefore, we evaluated the effects of pre-operative h-PTH treatment on cancellous bone union and its mechanism for fracture healing in ovariectomized rats as a model for osteoporosis. Ovariectomized 7-month-old female Sprague-Dawley rats underwent an osteotomy of the proximal tibia as a fracture model, and h-PTH (30 μg/kg body weight) or vehicle was administered as a pre-operative treatment for one week. After the one-week treatment, tibiae were fixed with wire for osteosynthesis, and h-PTH or vehicle was administered for 1 or 3 weeks following wire fixation. In addition to bone histomorphometry, we used alcian blue/hematoxylin stained sections for evaluating cartilage volume and immunostained sections for analyzing the expression of proliferating cell nuclear antigen (PCNA) for cell proliferation and that of Sox9 and Runx2, differentiation markers for cartilage cells and osteoblasts, respectively. Pre-operative treatment with PTH significantly increased bone volume. Pre-operative and pre- to post-operative treatment with PTH for 2 weeks significantly promoted bone union. Pre-operative treatment with PTH significantly increased cartilage volume, and pre- to post-operative treatment with PTH for 2 weeks significantly increased the percentage of cells positive for Runx2 (p < 0.01), but not PCNA or Sox9. Pre-operative administration of h-PTH enhances bone union by promoting cartilage formation and cell differentiation to osteoblasts, but not by promoting cell proliferation.
Patients suffering from autoimmune rheumatic diseases have significantly higher risk of developing various infections compared to the healthy population. Our study included patients suffering from systemic lupus erythematosus (n = 30), rheumatoid arthritis (n = 37) or Sjögren's syndrome (n = 32), with stable underlying diseases status. In November 2010, 47 patients, including 35 subjects vaccinated annually during 2006-2010, received immunization against influenza with trivalent inactivated split vaccine, whereas 52 patients did not accept proposed vaccination in that period. The presence of viral (primarily influenza) and bacterial infections, parameters of disease activity (from the date of vaccination until April 2011), and titers of antibodies against A H1N1 were then monitored in vaccinated and unvaccinated patients. We have identified the importance of predisposing factors for influenza occurrence (i.e. previous respiratory infections and vaccinations in last five years, age, sex, type of disease and duration, medications, smoking) in those groups of patients. The incidence of influenza or bacterial complications (bronchitis) among vaccinated patients was significantly lower, compared to the non-vaccinated group. Importantly, there was no case of exacerbation of the underlying disease. The last vaccination in 2010 reduced the risk of influenza by 87%, but previous bacterial infections (bronchitis and pneumonia) increased influenza risk significantly. In the present study, we have shown the efficiency, sufficient immunogenicity and safety of modern influenza vaccine application in patients suffering from systemic lupus erythematosus, rheumatoid arthritis or Sjögren's syndrome.
Liver fibrosis represents the final common pathway of virtually all types of chronic liver diseases, and it has been a major public health concern. Many genes have been demonstrated to be involved in the pathogenesis of liver fibrosis, while the mechanisms underlying gene regulation still needs further research. On the other hand, hepatic stellate cells (HSCs) are quiescent cells in the perisinusoidal space in liver. HSCs facilitate hepatocytes interactions via releasing soluble inflammatory factors and producing extracellular matrix. HSCs can be activated in response to liver injury, and they differentiate to myofibroblasts, which greatly contribute to the fibrogenesis process. Various epigenetic procedures, including DNA methylation, histone modification and formation of particular chromatin structure, play crucial roles in the gene transcriptional expression in HSCs, regulating various vital processes. For instance, epigenetic modulation on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene promoter accounts for HSC differentiation through interacting pathways. Aberrant expression of a series of histones and chemokines in activated HSCs can aggravate inflammation and oxidative stress, which in turn promotes differentiation of HSCs to myofibroblasts and enhances the whole fibrogenesis process. Degradation of extracellular matrix is also regulated through epigenetic modulation on matrix associated enzymes. Moreover, fibrosis-related epigenetic modifications in the parental generation may be inherited to their offspring. In this review, we firstly summarize the vital epigenetic modifications of fibrosis-related genes in HSCs, and highlight specific nucleic acid sequences and structures in gene promoters as important action sites, which may provide indicators for liver fibrosis diagnosis in the future.
Aldehyde dehydrogenase-2 (ALDH2) is the main enzyme responsible for acetaldehyde oxidation in ethanol metabolism and also provides protection against oxidative stress. Alpha-lipoic acid (α-LA), a natural dithiol compound with antioxidant properties, has been reported to increase ALDH2 activity in cultured cells. We analyzed the therapeutic efficacy of α-LA in 63 patients with confirmed acute coronary syndrome (ACS). These patients (52 men and 11 women, with age range 49-72 years) were randomized into two groups: untreated group (n = 30) and α-LA group (n = 33). Patients in the α-LA group were given an intravenous injection of 600 mg α-LA every day for 5 days while the patients in the untreated group were given saline. An isoprostane, 8-iso-prostaglandin F2α (8-iso-PGF2α), one product of arachidonic acid metabolism, was measured as a marker for oxidative stress. The serum levels of 8-iso-PGF2α and ALDH2 activity were determined at admission to the hospital (time 0), and at 24 hours and 1 week after treatment. At 24 hours and 1 week after treatment, ALDH2 activity was significantly higher in the α-LA group than in the untreated group (P < 0.05), whereas the levels of 8-iso-PGF2α were significantly lower in the α-LA group than in the untreated group (all P < 0.05). Importantly, the decrease of 8-iso-PGF2α levels correlated with the increased ALDH2 activity at both 24 hours (r = 0.6234, P < 0.001) and 1 week after treatment (r = −0.3941, P = 0.0014). α-LA may ameliorate oxidative stress through up-regulating ALDH2 activity in patients with ACS.
Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with β-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of β-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with β-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.
Lymphatic malformation (LM), which was previously termed lymphangioma, is a rare congenital malformation of the lymphatic system and its treatment is still challenging. Propranolol (beta blocker) has been recently developed as a first-line treatment of infantile hemangioma. Our study aimed to assess the effect of propranolol on pediatric LM and the relationship between its effectiveness and vascular endothelial growth factor (VEGF) family members (VEGF-A, C and D). Six Japanese patients with LM (age range: 10 months-19 years old; 2 macrocystic, 2 microcystic and 2 combined type) were enrolled. Oral propranolol was administered at 2 mg/kg/day. The efficacy of propranolol for LM was evaluated by the rate of volume change as calculated from MRI imaging and by symptomatic improvement. In all patients, there were no significant side effects. Patients 3 and 5 were classified as objective responders with tumor volume reduction of 30.6% and 22.9%, respectively, at 24 weeks. Patient 1 showed 8% tumor volume reduction and patient 6 showed symptomatic improvement, hence, both were classified as minimal responders. The other two patients were classified as non-responders. Plasma VEGF-A, C, and D levels were significantly higher in the LM group than in the controls (all P < 0.01 by Mann-Whitney test). VEGF-A and D levels at 24 weeks were significantly lower than those at pre-treatment (P = 0.031, 0.047 by Wilcoxon matched pairs test). Though further trials with this treatment must be carried out, we propose that propranolol may be an alternative therapy option for intractable LM.
Rhythmical contraction of the heart is controlled by the cardiac conduction system (CCS) that consists of the three main parts: the sino-atrial node, the atrioventricular node and the His-Purkinje system. A heartbeat signal, originated from CCS, spreads through its branches to the different parts of the heart, initiating depolarization of the ventricles. However, this highly important system could not be distinguished visually from the surrounding heart tissues: myocardium (MC) and connective tissue (CT). Thus, during surgical procedures, CCS could be easily damaged; namely, the reliable method for identification of CCS either in vivo or ex vivo does not exist. Accordingly, there is a definite need for developing a CCS imaging method. Reflection confocal microscopy (RCM) offers non-destructive imaging of the tissue at depths of up to 0.35 mm with the capability of identification of a single cell. During the visualization procedure, a given tissue is illuminated with infrared laser light and the image is obtained because of different reflections from the tissue structures. However, the reflective structures in the heart tissues are still not identified. In the present study, for the first time we investigated cardiac tissues by RCM. The resolution of the method allowed us to distinguish MC cells and CCS cells. The method also allowed us to distinguish the network-like structures that are main components of CT. The ability to visualize different tissue components indicates a great potential for RCM to be used in non-destructive cardiac investigations and for imaging CCS.
Small cell carcinoma of the uterine cervix (SCCC) is a rare subtype of cervical cancer with an aggressive behavior. Although SCCC has a worse prognosis than other histological types of uterine cervical cancer such as squamous cell carcinoma or adenocarcinoma, standard therapy for SCCC remains to be established due to its rarity. The purpose of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) using a regimen consisting of vincristine, adriamycin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE). We analyzed a series of 9 patients with SCCC. Five patients with stage IB disease underwent radical hysterectomy followed by CCRT. Four patients with advanced stage disease received CCRT primarily. With a median follow-up duration of 47.4 months (range, 10.5 to 86.4 months), 4 out of 5 patients with stage IB disease were alive without recurrence. In 4 patients with advanced stage disease, the response rate was 75% (complete response, 1; partial response, 2; progressive disease, 1). One patient with stage IVB disease remained without recurrence for 89.5 months. At 5 years, overall survival (OS) and progression-free survival for all patients was 52% and 56%, respectively. Patients with early-stage disease had an 80% 5-year OS rate compared to 25% for patients with advanced stage disease. Although all patients developed grade 3-4 neutropenia, CCRT using VAC/PE is feasible in both the primary and adjuvant settings for SCCC. In particular, this combined modality therapy may improve both local control and survival as postoperative treatment in patients with early-stage disease.
Tolosa-Hunt syndrome (THS) is a rare disorder, especially in the pediatric population, characterized by unilateral painful ophthalmoplegia with a relapsing-remitting course. Because the diagnosis of THS is based on the exclusion of other causes of painful ophthalmoplegia, attention should be paid to possible alternative diagnoses. Thallium-201 chloride (201Tl) scintigraphy has been used to evaluate tissue histology in clinical oncology with a marker, the retention index (RI). A higher value indicates histological malignancy. Although its utility in pediatric THS has not been discussed, we suggest that 201Tl scintigraphy may be informative as a marker in the diagnosis. We present an 11-year-old boy with THS who was evaluated with 201Tl scintigraphy before treatment with corticosteroids, when he had headache, photophobia, and diplopia. The RI of 201Tl indicated that the lesion would be benign. Although his clinical symptoms did not fulfill the THS criteria completely, his eye symptoms disappeared 2 weeks after corticosteroid treatment, which was not within the 72h as in the diagnostic criteria of THS. He has been symptom-free for more than 2years with only an initial 4-week corticosteroid therapy. This report not only shows the potential of 201Tl scintigraphy to contribute to the correct diagnosis of pediatric THS but also suggests the possibility that the diagnosis of THS could be supported uniquely even in a pediatric THS-suspicious patient who did not fulfill the current THS criteria completely. In conclusion, we suggest that 201Tl scintigraphy may be useful for making the diagnosis of THS, especially in pediatric patients.