Unilateral Retroorbital Pain Secondary to Isolated Sphenoid Sinus Aspergillosis

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Temporal Variation and Vertical Structure of the Marine Atmospheric Mixed Layer over the East China Sea from Mie-Scattering Lidar Data

The marine atmospheric mixed layer (MAML) has an important influence on the diffusion of air pollutants over the East China Sea. We analyzed seasonal and diurnal variations and the vertical structure of the MAML by using continuous Mie-scattering lidar data recorded from March 2008 to February 2010 at Cape Hedo, Okinawa Island, Japan. The height of the MAML showed clear seasonal variation: a summer minimum and a winter maximum, and was significantly correlated with thermal stability (St), which we defined as sea surface temperature minus the temperature at the 850 hPa level. The height of the MAML showed minor diurnal variations in summer: a nighttime minimum and a daytime maximum. We detected the entrainment layer between the MAML and the free atmosphere by analysis of the intensity of fluctuations of aerosol concentrations determined from lidar data. Both the intensity of the fluctuations and the thickness of the entrainment zone increased with increasing St. The altitude of maximum fluctuation was a little above the top of the MAML

Relationship between the cAMP levels in leukocytes and the cytokine balance in patients surviving gram negative bacterial pneumonia

Lipopolysaccharide-stimulated leukocytes secrete proinflammatory cytokines including tumor necrosis factor-α and interleukin-12. Over-activation of host defense systems may result in severe tissue damage and requires regulation. Granulocyte colony-stimulating factor and interleukin-10 are candidate cytokines for inducing tolerance to lipopolysaccharide re-stimulation. We compared cytokines secreted by lipopolysaccharide-stimulated blood cells from patients who had survived gram negative bacterial pneumonia (Pseudomonas aeruginosa, Escherichia coli or Proteus mirabilis, n = 26) and age-matched healthy volunteers (n = 18). Interleukin-12p70 and tumor necrosis factor-α expression was significantly lower in patients (p = 0.0039 and p<0.001) compared to healthy controls, while granulocyte colony-stimulating factor production was markedly higher in patients (p<0.001). Levels of interleukin-10 were comparable. Granulocyte colony-stimulating factor expression was inversely correlated with interleukin-12p70 (R = −0.71, p<0.001) and tumor necrosis factor-α (R = −0.64, p<0.001) expression; interleukin-10 showed no significant correlation. In unstimulated leukocytes from patients, cAMP levels were significantly raised (p = 0.020) and were correlated inversely with interleukin-12p70 levels (R = −0.81, p<0.001) and directly with granulocyte colony-stimulating factor (R = 0.72, p = 0.0020), matrix metalloproteinase-9 (R = 0.67, p = 0.0067) and interleukin-10 (R = 0.54, p = 0.039) levels. Our results demonstrate that granulocyte colony-stimulating factor production by lipopolysaccharide-stimulated leukocytes is a useful indicator of tolerance induction in surviving pneumonia patients and that measuring cAMP in freshly isolated leukocytes may also be clinically significant

Mid-term results of computer-assisted cervical reconstruction for rheumatoid cervical spines

Study design A retrospective single-center study. Summary and background We routinely have used C1-C2 transarticular and cervical pedicle screw fixations to reconstruct highly destructed unstable rheumatoid arthritis (RA) cervical lesions. However, there is little data on midterm results of surgical reconstruction for rheumatoid cervical disorders, particularly, cervical pedicle screw fixation. Objectives The purpose of this study was to evaluate the mid-term surgical results of computer-assisted cervical reconstruction for such lesions. Methods Seventeen subjects (4 men, 13 women; mean age, 61 +/- 9 years) with RA cervical lesions who underwent C1-C2 transarticular screw fixation or occipitocervical fixation, with at least 5 years follow-up were studied. A frameless, stereotactic, optoelectronic, CT-based image-guidance system, was used for correct screw placement. Variables including the Japanese Orthopaedic Association (JOA) score, Ranawat class, EuroQol (EQ-5D), atlantodental interval, and Ranawat values before, and at 2 and 5 years after surgery, were evaluated. Furthermore, screw perforation rates were evaluated. Results The lesions included atlantoaxial subluxation (AAS, n = 6), AAS + vertical subluxation (VS, n = 7), and AAS + VS + subaxial subluxation (n = 4). There was significant neurological improvement at 2 years after surgery, as evidenced by the JOA scores, Ranawat class, and the EQ-5D utility weight. However, at 5 years after surgery, there was a deterioration of this improvement. The Ranawat values before, and at 2 and 5 years after surgery, were not significantly different. Major screw perforation rate was 2.1 %. No neural and vascular complications associated with screw insertion were observed. Conclusions Subjects with rheumatoid cervical lesions who underwent C1-C2 transarticular screw fixation or occipitocervical fixation using a pedicle screw had significantly improved clinical parameters at 2 years after surgery. However, there was a deterioration of this improvement at 5 years post surgery.ArticleJOURNAL OF ORTHOPAEDIC SCIENCE. 18(6):916-925 (2013)journal articl

ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles

Rho-associated kinase (ROCK) I mediates signaling from Rho to the actin cytoskeleton. To investigate the in vivo functions of ROCK-I, we generated ROCK-I–deficient mice. Loss of ROCK-I resulted in failure of eyelid closure and closure of the ventral body wall, which gave rise to the eyes open at birth and omphalocele phenotypes in neonates. Most ROCK-I−/− mice died soon after birth as a result of cannibalization of the omphalocele by the mother. Actin cables that encircle the eye in the epithelial cells of the eyelid were disorganized and accumulation of filamentous actin at the umbilical ring was impaired, with loss of phosphorylation of the myosin regulatory light chain (MLC) at both sites, in ROCK-I−/− embryos. Stress fiber formation and MLC phosphorylation induced by EGF were also attenuated in primary keratinocytes from ROCK-I−/− mice. These results suggest that ROCK-I regulates closure of the eyelids and ventral body wall through organization of actomyosin bundles

Development of eosinophilic granulomatosis with polyangiitis during the clinical course of microscopic polyangiitis: A case report

Rationale: Eosinophilic granulomatosis with polyangiitis (EGPA) is belongs to the antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) subgroups. EGPA, unlike other subgroups of AAV, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis, has the unique feature that both ANCA and eosinophilic inflammation are involved in its pathogenesis. Although AAV often relapses, there are currently no reports of EGPA developing during other subgroups of AAV. Herein, we document a case of EGPA that developed during the clinical course of MPA.Patient concerns: A 61-year-old Japanese woman was diagnosed with MPA based on interstitial lung disease and myeloperoxidase-ANCA positivity. After starting immunosuppression therapy, including prednisolone and tacrolimus, she was expected to achieve clinical remission. Nonetheless, she occasionally experienced MPA relapse, which required an increased prednisolone dose, rituximab, intravenous cyclophosphamide, and plasma exchange. Three years after MPA onset, she developed renal amyloidosis; thus, subcutaneous tocilizumab was added to her regimen. Following clinical remission, the administration interval of her subcutaneous tocilizumab therapy was extended and immunosuppressants were discontinued. She then developed bronchial asthma and mild eosinophilia (eosinophilic count: ~1000/μL). Further, a year later, she underwent total hip replacement using a titanium implant. Subsequently, she developed abnormal sensation in both hands, numbness, and muscle weakness, as well as palpable purpura and massive eosinophilia (eosinophilic count: ~8500/μL).Diagnosis: We diagnosed the patient with EGPA based on 5 items (asthma, multiple mononeuropathies, sinus abnormality, and extravascular eosinophils) of the 1990 American College of Rheumatology classification criteria.Interventions: We administered 400 mg/kg intravenous immunoglobulin for 5 consecutive days, 300 mg mepolizumab subcutaneously every 4 weeks, and 40 mg/day prednisolone following pulsed methylprednisolone therapy (1000 mg/day for 3 consecutive days).Outcomes: After these treatments, the patient’s symptoms improved, and eosinophilic count and inflammatory markers declined.Lessons: The present case suggests that EGPA can be induced by the development of eosinophilic inflammation in other subgroups of AAV.Abbreviations: AAV = ANCA-associated vasculitis, ANCA = antineutrophil cytoplasmic autoantibody, CCL = chemokine (C–C motif) ligands, CRP = C-reactive protein, EGPA = eosinophilic granulomatosis with polyangiitis, IL = interleukin, ILC2 = group 2 innate lymphoid cells, ILD = interstitial lung disease, MPA = microscopic polyangiitis, MPO = myeloperoxidase, mPSL = methylprednisolone, PSL = prednisolone, TAC = tacrolimus, TCZ = tocilizumab, Th2 = T helper 2

Myxopapillary Ependymoma of the Cauda Equina in a 5-Year-Old Boy

Myxopapillary ependymoma in childhood typically occurs in the central nervous system. There are few surgical cases of myxopapillary ependymoma of the cauda equina in children. We report a case of myxopapillary ependymoma of the cauda equina in a 5-year-old boy, who presented with leg pain and abnormal gait. Subtotal resection surgery was performed. Following the subtotal tumor resection, follow-up magnetic resonance imaging evaluation showed a recurrent tumor. As a result, we performed a second subtotal tumor resection and followed with postoperative radiation therapy. No further evidence of the disease has been noted elsewhere in the patient in over ten years of follow-up. Myxopapillary ependymoma of the cauda equina in a young boy was improved by subtotal tumor resection and postoperative radiation therapy

Discontinuation of methotrexate in rheumatoid arthritis patients achieving clinical remission by treatment with upadacitinib plus methotrexate (DOPPLER study)

Background: The administration of Janus kinase inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved the clinical outcomes of patients with rheumatoid arthritis (RA). Previous trials have shown that upadacitinib, a Janus kinase inhibitor, can effectively improve disease activity and prevent progression of joint destruction in RA patients with inadequate responses to methotrexate (MTX). It remains unclear whether reduced disease activity can be maintained after discontinuation of MTX in patients treated with upadacitinib plus MTX. Thus, the aim of this study is to evaluate changes in disease activity after administration of upadacitinib plus MTX in RA patients who failed to achieve an adequate response to MTX and to determine whether clinical relapse can be avoided after discontinuation of MTX in those who achieved clinical remission.Methods/design: The proposed study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. The cohort will include 155 RA patients with at least moderate disease activity during treatment with MTX. Patients will receive upadacitinib and MTX will be discontinued for those who achieve clinical remission. Disease activity will be evaluated longitudinally by measuring clinical disease activity indices and with musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who sustain a disease activity score-28- C reactive protein score of ≤3.2 from week 24 to 48 after a disease activity score-28- C reactive protein score of <2.6 at week 24. Important secondary endpoints are changes from baseline MSUS scores. Serum levels of multiple biomarkers, including cytokines and chemokines, will be comprehensively analyzed.Discussion: The study results are expected to show the clinical benefit of the discontinuation of MTX after achieving clinical remission by treatment with upadacitinib plus MTX combination therapy. The strength of this study is the prospective evaluation of therapeutic efficacy using clinical disease activity indices and standardized MSUS, which can accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers. Furthermore, parameters to predict clinical remission after administration of upadacitinib plus MTX combination therapy and nonclinical relapse after discontinuation of MTX will be screened by integrated multilateral assessments (i.e., clinical disease activity indices, MSUS findings, and serum biomarkers)