Erythropoietin (EPO) promotes red blood cell production thereby raising oxygen transport ability. Epo gene expression is positively controlled by hypoxia-inducible factor (HIF) through the HIF binding site in an Epo gene enhancer; and negatively controlled by GATA, which binds to the GATA site in the Epo gene promoter. Drugs that activate HIF (FG-2216) or inhibit GATA (K-11706) increase the production of EPO. Therefore, these drugs might be illicitly used to improve performance in sports as new doping practices. To develop a system for detecting such a doping strategy, we performed DNA microarray and quantitative RT-PCR to compare the effects of FG-2216^*, the derivative of FG-2216, and K-11706, on gene expression with that of recombinant human EPO (rhEPO) or hypoxia in mice. Gene expression analysis in bone marrow cells showed increased expression of Lactoperoxidase (Lpo) only in the mice treated with K-11706, and decreased expression of Oncostatin M (Osm) with FG-2216^* or hypoxia, but not with K-11706. Results to date suggest that gene expression changes observed in using these drugs have the potential to yield novel biomarkers in a detection system for new illicit drug use.

Garré's osteomyelitis is generally considered to be synonymous with chronic osteomyelitis with proliferative periostitis and occurs most commonly in the first molar region of the mandible. We report a case of Garré's osteomyelitis caused by the infected tooth-germ of a wisdom tooth. A 12-year-old boy had a swelling of the right cheek and his right mandibular second molar was covered by gingiva with pus retention. X-ray examination showed a radiolucent area around the impacted tooth-germ of the wisdom tooth and extracortical new bone at the angle of the mandible. After preoperative treatment with antibiotics, the tooth-germ and extracortical bone were removed. The antibiotics treatment was continued for 18 days postoperation. No recurrence of pain or swelling has been observed thereafter.

Methods: We examined the computed tomography scans from the thoracic vertebra to the sacrum used to diagnose DISH in 140 patients (98 men and 42 women; average age, 78.6 years). We compared patients who did (n=52) and did not have (n=88) fractures at the continuous vertebral bodies fused by bone bridges. The relationship between the vertebral fractures and the maximum number of vertebrae that are bony cross-linked with contiguous adjacent vertebrae (max VB) from the thoracic vertebra to the sacrum or from the lumbar vertebra to the sacrum and proximal femur BMD were analyzed using a logistic regression model. Results: We found that after adjusting for the confounding factors, higher max VB, both from the thoracic vertebrae to the sacrum and the lumbar vertebrae to the sacrum, was associated with a higher risk of vertebral fractures. This difference was statistically significant. The risk was higher when only the lumbar vertebrae to the sacrum was considered (thoracic vertebrae to the sacrum: odds ratio, 1.21; p<0.05; lumbar vertebrae to the sacrum: odds ratio, 2.78; p<0.01). Moreover, low proximal femur BMD in DISH patients raises the fracture risk (odds ratio, 0.47; p<0.01). Conclusions Many continuous vertebral bone bridges, especially those that extend to the lumbar spine and low proximal femur BMD, are risk factors for fracture in DISH patients.

The UBE woven 150cc WYK graft is a non-sealed graft that became available commercially in January 2005, and does not need to be preclotted before implantation. Subjects in this study comprised 50 patients with abdominal aortic aneurysms or common iliac arterial aneurysms, who received prosthetic Y grafts in our institution. Subjects were divided into 2 groups: the U group (n=26), with implantation of the UBE graft, and the I group (n=24) who received implantation of an INTERGARD^TM woven Y graft. Intraoperative bleeding, inflammatory response and duration of postoperative hospitalization were evaluated in each group. Significant differences were noted between C-reactive protein levels, frequency of recurrence of fever and duration of postoperative hospitalization. No differences were noted between intraoperative bleeding and time. The UBE woven 150cc WYK graft, compared with the INTERGARD^TM woven Y graft, required no extra time for implantation and appeared to offer advantages such reduced immunoreaction after surgery. However, follow-up for sufficient late-phase evaluation of the grafts is required.

BACKGROUND/AIMS: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. METHODS: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. RESULTS: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. CONCLUSIONS: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy.
Adsorption ; Arm ; Blood Component Removal ; Colitis, Ulcerative ; Extracorporeal Circulation ; Humans ; Inflammatory Bowel Diseases ; Prednisolone ; Prospective Studies ; Recurrence ; Remission Induction ; Salicylamides ; Ulcer

BACKGROUND/AIMS: Cytapheresis (CAP) is a novel strategy for ulcerative colitis (UC). However, there is insufficient data on the long-term outcome of UC patients who achieve remission by CAP. This study involved patients with severe UC who refracted to intravenous (iv) corticosteroid. METHODS: Forty-seven UC patients who had received CAP therapy for the first time within 1 year after UC diagnosis were followed for 36 months. One of the inclusion criteria was a clinical activity index (CAI) of > or =7 points at the end of a 2-week iv course of corticosteroid therapy. CAP therapy consisted of ten sessions over 10 weeks. RESULTS: CAP induced clinical remission (CAI< or =4) in 70.2% patients (33/47). The number of submissions for colectomy was higher for severe UC at entry (CAI> or =12, n=25) than for moderately severe UC at entry (7< or =CAI<12, p=15; p<0.02). The cumulative rates of avoiding surgery and relapse were 54.5% and 24.2%, respectively, at 36 months in patients who responded to CAP therapy. This was similar to that of iv cyclosporine reported recently. CONCLUSIONS: This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC.
Cohort Studies ; Colectomy ; Colitis, Ulcerative ; Cyclosporine ; Cytapheresis ; Humans ; Inflammatory Bowel Diseases ; Leukapheresis ; Recurrence ; Retrospective Studies ; Ulcer

BACKGROUND/AIMS: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-alpha has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX. METHODS: Twenty-two patients with a CD activity index (CDAI) of 194.2+/-92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their first IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. RESULTS: CDAI significantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-beta1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-alpha (p<0.04), IL-6 (p<0.03), interferon (IFN)-gamma (p<0.04), IFN-gamma-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1beta (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-gamma)/Th2 (IL-4) ratio (p<0.03). CONCLUSIONS: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance.
Antibodies ; Antibodies, Monoclonal ; Chemokine CCL2 ; Chemokine CCL5 ; Chemokines ; Crohn Disease ; Cytokines ; Humans ; Immune System ; Interferons ; Interleukin-10 ; Interleukin-13 ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Lymphocytes ; Macrophages ; Mesalamine ; Remission Induction ; T-Lymphocytes, Regulatory ; Tumor Necrosis Factor-alpha ; Infliximab

Purpose: To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. Materials and Methods: This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community-dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. Results: The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Conclusions Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels.

Methods: This study analyzed 143 patients who underwent decompression surgery between 2012 and 2014, who had symptomatic cervical disorders and MRI evidence of spinal cord or nerve compression but had no history of cervical spine surgery. Patient demographics, disease type, Japanese Orthopedic Association score, and follow-up periods were recorded. Spinal surgeons conducted radiological evaluations to determine stenosis levels using computed tomography myelography or MRI in neutral and extended positions. Measurements such as dural tube and spinal cord diameters, cervical alignment, range of motion, and various angles and distances were also analyzed. The residual space available for the spinal cord (SAC) was also calculated. Results: During extension, new stenosis frequently appeared caudal to the stenosis site in a neutral position, particularly at C5/C6 and C6/C7. A low SAC was identified as a significant risk factor for the development of new stenosis in both the upper and lower adjacent disc levels. Each 1-mm decrease in SAC resulted in an 8.9- and 2.7-fold increased risk of new stenosis development in the upper and lower adjacent disc levels, respectively. A practical SAC cutoff of 1.0 mm was established as the threshold for new stenosis development. Conclusions The study identified SAC narrowing as the primary risk factor for new stenosis, with a clinically relevant cutoff of 1 mm. This study highlights the importance of local factors in stenosis development, advocating for further research to improve outcomes in patient with cervical spine disorders.

BACKGROUND: The July 2018 Japan Floods caused enormous damage to western Japan. Such disasters can especially impact elderly persons. Research has shown that natural disasters exacerbated a decline in cognitive function, but to date, there have been no studies examining the effects of this disaster on the elderly. The object of this study was to reveal the effect of this disaster in terms of cognitive decline among the elderly. METHODS: Study participants were certified users of the long-term care insurance (LTCI) system in Hiroshima, Okayama, and Ehime prefectures from May 2018 to June 2018. The observation period was from July 2018 to December 2018. Our primary outcome was cognitive decline after the disaster using a dementia symptomatology assessment. In addition to a crude model, a multivariate Cox proportional hazards model was used to assess the cognitive decline of victims, adjusting for age classification, gender, the level of dementia scale before the disaster occurred, residential environment, whether a participant used facilities shut down after the disaster, and population density. After we confirmed that the interaction term between victims and residential environment was statistically significant, we stratified them for the analysis. RESULTS: The total number of participants was 264,614. Victims accounted for 1.10% of the total participants (n = 2,908). For the Cox proportional hazards model, the hazard ratio of the victims was 1.18 (95% confidential interval (CI): 1.05-1.32) in the crude model and 1.12 (95% CI: 1.00-1.26) in the adjusted model. After being stratified by residential environment, the hazard ratio of home victims was 1.20 (95% CI: 1.06-1.36) and the hazard ratio of facility victims was 0.89 (95% CI: 0.67-1.17). CONCLUSIONS This study showed that elderly living at home during the 2018 Japan Floods were at risk for cognitive decline. Medical providers, care providers, and local governments should establish a system to check on the cognitive function of elderly victims and provide necessary care support.
Aged ; Cognitive Dysfunction/etiology* ; Floods ; Humans ; Insurance, Long-Term Care ; Japan/epidemiology* ; Retrospective Studies