Rhino-Orbito-Cerebral Mucormycosis in an Immunocompromised Patient

Rhino-orbito-cerebral mucormycosis (ROCM) is an invasive fungal infection that usually occurs in immunocompromised patients. It is aggressive and has a high risk of mortality. With unclear guidelines, ROCM is treated in various ways. We present a patient who underwent kidney transplant and who treated for ROCM without major complications.

Genetic Variants and Clinical Phenotypes in Korean Patients With Hereditary Hemorrhagic Telangiectasia

Objectives@#. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. @*Methods@#. Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. @*Results@#. In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. @*Conclusion@#. Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Intralymphatic allergen-specific immunotherapy

Although allergen-specific immunotherapy (AIT) is a standard treatment for allergic diseases, only 5% or less of patients in whom AIT is indicated have been receiving immunotherapy because AIT needs a long-term therapeutic duration of up to 5 years. To overcome this limitation of conventional AIT, Kündig and his colleagues first introduced intralymphatic immunotherapy (ILIT) in patients with allergic rhinitis, publishing their results in 2008. Since then, 10 clinical trials that evaluated therapeutic efficacies and adverse effects of ILIT have been conducted. This article reviews the clinical trials of ILIT and suggests unmet needs in research fields of ILIT.

Usefulness of Unilateral Nasal Packing for Recurred Septal Deviation within a Month after Septoplasty: Preliminary Study

BACKGROUND AND OBJECTIVES: To investigate the effect of unilateral nasal packing on the correction of recurred septal deviation after septoplasty. MATERIALS AND METHOD: We analyzed 12 patients who had undergone septoplasty and developed septal deviation recurrence. Polyvinylacetate and Vaseline gauze were inserted into the nasal passage on the convex side of the septum for 4 days in order to shift the septum to the midline. We analyzed nasal symptoms, acoustic rhinometric results, and endoscopic findings before and after unilateral packing in order to evaluate the treatment outcomes. RESULTS: Ten (83%) out of 12 patients showed improvements in nasal obstruction, acoustic rhinometric results, and endoscopic findings. The mean visual analogue scale (VAS) score for nasal obstruction was 5.25±1.60 before and 2.08±1.50 after packing (p=0.004). The minimal cross-sectional area (MCA) improved from 0.17±0.14 to 0.27±0.13 (p=0.002), and the mean endoscopic score improved from 2.0±0.43 to 1.08±0.29 (p=0.002). CONCLUSION: Unilateral nasal packing was a safe, easy, and effective method for correcting recurred septal deviation after septoplasty.

Intralymphatic Immunotherapy Alleviates Allergic Symptoms During Allergen Exposure in Daily Life

No abstract available.

Allergen Microarrays for In Vitro Diagnostics of Allergies: Comparison with ImmunoCAP and AdvanSure

BACKGROUND: In vitro detection of the allergen-specific IgE antibody (sIgE) is a useful tool for the diagnosis and treatment of allergies. Although multiple simultaneous allergen tests offer simple and low-cost screening methods, these platforms also have limitations with respect to multiplexibility and analytical performance. As an alternative assay platform, we developed and validated a microarray using allergen extracts that we termed “GOLD” chip. METHODS: Serum samples of 150 allergic rhinitis patients were used in the study, and the diagnostic performance of the microarray was compared with that of AdvanSure (LG Life Sciences, Daejun, Korea) and ImmunoCAP (Phadia, Uppsala, Sweden). Standard IgE samples were used for the quantitative measurement of sIgEs. RESULTS: The microarray-based assay showed excellent performance in the quantitative measurement of sIgEs, demonstrating a linear correlation within the range of sIgE concentrations tested. The limit of detection (LOD) was lower than 0.35 IU/mL, which is the current standard for the LOD cut-off. The assay also provided highly reproducible sets of data. The total agreement percentage of positive and negative calls was 92.2% compared with ImmunoCAP. Moreover, an outstanding correlation was observed between the microarray and the ImmunoCAP results, with Cohen's kappa and Pearson correlation coefficient values of 0.80 and 0.79, respectively. CONCLUSIONS: The microarray-based in vitro diagnostic platform offers a sensitive, reproducible, and highly quantitative method to detect sIgEs. The results showed strong correlations with that of ImmunoCAP. These results suggest that the new allergen microarray can serve as a useful alternative to current screening platforms, ultimately becoming a first-line screening method.

Low Concentration PM10 Had No Effect on Nasal Symptoms and Flow in Allergic Rhinitis Patients

OBJECTIVES: Since Korea is geographically close to China (the origin site for Asian sand dust [ASD]) the health influence of ASD event will be still greater in Korea. We aimed to evaluate the effect of PM₁₀ (particulate matter with aerodynamic diameter 100 μg/m³) RESULTS: There was no significant difference between group A and B in nasal symptoms and PNIF during the 120-day period. Changes in nasal symptoms and PNIF were not statistically significant before or after a PM₁₀ concentration rise above 100 μg/m³. CONCLUSION: Low concentration PM10 does not have significant effect on nasal symptoms and PNIF in AR patients.

A Pilot Study of Intralymphatic Immunotherapy for House Dust Mite, Cat, and Dog Allergies

Several recent clinical trials reported that intralymphatic immunotherapy (ILIT) for some allergens, such as cat dander and pollen, induce tolerance more rapidly than conventional subcutaneous or sublingual immunotherapy, have a comparable duration of effect after only 3 injections, and do not provoke serious local or systemic reactions. However, the efficacy and safety of ILIT are using Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), and dog, which are indoor allergens that are commonly found globally, need to be evaluated. Furthermore, use of multiple allergens in ILIT should be investigated. We assessed the clinical efficacy and adverse effects of ILIT using aqueous Df, Dp, dog, and cat allergens or mixtures thereof in patients with allergic rhinitis. A total of 11 subjects with AR sensitized to Df, Dp, cat, and/or dog allergens received 3 intralymphatic inguinal injections of sensitized allergen extract (HollisterStier, New Orleans, LA, USA). Clinical parameters were assessed before ILIT, and 4 months and 1 year after the first injection. Rhinitis symptoms were alleviated and quality of life was improved 4 months after ILIT (P=0.012 and P=0.007, respectively), and these improvements lasted for 1 year after ILIT (P=0.047 and P=0.009, respectively). However, we observed 2 cases of anaphylaxis, one case of a moderate-to-severe systemic hypersensitivity reaction and the other case of a severe local reaction at the injection site after ILIT. In conclusion, ILIT can rapidly improve allergy symptoms and quality of life, and this effect lasts for 1 year. In hypersensitized patients, however, ILIT can provoke severe systemic and/or local hypersensitivity reactions when performed using aqueous allergen extracts.

A Case of Rhinosporidiosis of the Nasal Cavity / 대한이비인후과학회지

Rhinosporidiosis is a chronic granulomatous infectious disease caused by Rhinosporidium seeberi, which is endemic to South India, Sri Lanka, and parts of Africa. It is primarily an infection of the nose. Although involvement of other parts of body has occasionally been reported, it rarely presents as a disseminated disease. We describe a case of nasal rhinosporidiosis in Korea and discuss its clinical manifestations and management.

Analysis of Characteristics and Steroid Effects in Olfactory Dysfunction Patients

BACKGROUND AND OBJECTIVES: Olfactory dysfunction is a common sensory disorder, but there are currently no standard diagnostics or therapeutic methods. We analyzed the effects of systemic steroid therapy in patients with olfactory dysfunction. MATERIALS AND METHOD: We analyzed patients who visited our ENT department with olfactory dysfunction for 3 years. We reviewed their charts and classified the patients according to age, sex, etiology of olfactory dysfunction, degrees of olfactory dysfunction and the effect of systemic steroid therapy. RESULTS: The mean age was 44.3 years old and there were 50 males and 55 females; 55 patients had inflammatory disease and 50 patients had non-inflammatory disease. The distribution of degrees of olfactory disorder according to cause was not significantly different (p=0.120). In 105 patients, 20% experienced improvements after systemic steroid therapy, and the response of systemic steroid therapy was better among patients with inflammatory causes. In cases of inflammatory disease, there was a larger amount of severe hyposmia patients, and their response to systemic steroid therapy was significant (p=0.015). Patients with mild and moderate hyposmia were more responsive to systemic steroid therapy than patients with severe hyposmia (p=0.382). CONCLUSION: In cases of hyposmia due to inflammatory disease, systemic steroid therapy with proper operative management may increase therapeutic effects.

In vivo Tracking of Dendritic Cell using MRI Reporter Gene, Ferritin.

The noninvasive imaging of dendritic cells (DCs) migrated into lymph nodes (LNs) can provide helpful information on designing DCs-based immunotherapeutic strategies. This study is to investigate the influence of transduction of human ferritin heavy chain (FTH) and green fluorescence protein (GFP) genes on inherent properties of DCs, and the feasibility of FTH as a magnetic resonance imaging (MRI) reporter gene to track DCs migration into LNs. FTH-DCs were established by the introduction of FTH and GFP genes into the DC cell line (DC2.4) using lentivirus. The changes in the rate of MRI signal decay (R2*) resulting from FTH transduction were analyzed in cell phantoms as well as popliteal LN of mice after subcutaneous injection of those cells into hind limb foot pad by using a multiple gradient echo sequence on a 9.4 T MR scanner. The transduction of FTH and GFP did not influence the proliferation and migration abilities of DCs. The expression of co-stimulatory molecules (CD40, CD80 and CD86) in FTH-DCs was similar to that of DCs. FTH-DCs exhibited increased iron storage capacity, and displayed a significantly higher transverse relaxation rate (R2*) as compared to DCs in phantom. LNs with FTH-DCs exhibited negative contrast, leading to a high R2* in both in vivo and ex vivo T2*-weighted images compared to DCs. On histological analysis FTH-DCs migrated to the subcapsular sinus and the T cell zone of LN, where they highly expressed CD25 to bind and stimulate T cells. Our study addresses the feasibility of FTH as an MRI reporter gene to track DCs migration into LNs without alteration of their inherent properties. This study suggests that FTH-based MRI could be a useful technique to longitudinally monitor DCs and evaluate the therapeutic efficacy of DC-based vaccines.

Comparison of Component-Resolved Diagnosis by Using Allergen Microarray With the Conventional Tests in Allergic Rhinitis Patients: The First Using in Korea

OBJECTIVES: The aim of this study was to evaluate the component-resolved diagnosis using a microarray allergen chip (Immuno Solid-phase Allergen Chip, ImmunoCAP ISAC) and to compare this new diagnostic tool with the established ImmunoCAP methods for allergen-specific IgE detection in allergic rhinitis patients. METHODS: One hundred sixty-eight allergic rhinitis patients were included in this study. All the patients were diagnosed with allergic rhinitis according to their clinical symptoms, physical examination and a positive skin prick test. We analyzed their specific IgEs for house dust mites (Dermatophagoides farine [DF] and Dermatophagoides pteronyssinus [DP]), Alternaria alternata, birch, and mugwort using ImmunoCAP and ImmunoCAP ISAC in the same patient sample. We compared the sensitivity and correlation between the two tests. RESULTS: In cases of allergies to DP and DF, the sensitivity of the specific IgE was 80% and that of the allergen microarray was 78.9%. The correlation between the two tests was significant for both DP and DF (P<0.001). For the A. alternata, birch and mugwort allergens, the sensitivity of ImmunoCAP ISAC was slightly lower than that of ImmunoCAP. CONCLUSION: These results suggest that the allergen microarray chip method is a reliable new method to diagnose the components of an allergen in patients with allergic rhinitis sensitive to house dust mites. Further study about the utility of the allergen microarray is needed.

Two Cases of Rhinocerebral Mucormycosis

Mucormycosis is a rare opportunistic fungal infection. The most common infection site is the paranasal sinuses, although it can also occur in the lungs and skin. The fungus adheres to tissue membranes and forms thrombi, causing ischemia and hemorrhagic necrosis. Rhinocerebralmucormycosiscan occurin the nose, but mightrapidly spread to the orbit and intracranium. Therefore, prompt and aggressive treatment is required. However, because of its low incidence, few reported cases have focused on accompanying disease, proper treatment period, and disease progression. Herein, we report two cases of rhinocerebralmucormycosiswith a brief literature review.

Reconstruction of a Columellar Defect With a Nasolabial Island Flap

Columellar skin defects may be caused by excision of cutaneous malignancy, trauma, or tissue necrosis associated with surgery. Although columellar skin necrosis rarely occurs following rhinoplasty, this condition might be more common when using an external approach than a closed approach. Columellar skin incision performed with exaggerated tip augmentation may cause columellar necrosis. The nasolabial island flap, used unilaterally to cover columellar skin defects, is used for a single-stage reconstruction procedure and is generally not associated with the need for secondary surgeries. This technique is well suited for repairing columellar skin defects. We experienced a patient with columellar skin necrosis occurring after rhinoplasty which was reconstructed using a unilateral single-stage nasolabial island flap.

In vivo magnetic resonance imaging of transgenic mice expressing human ferritin.

OBJECTIVE: This study aims to produce the transgenic mice (TG) engineered for magnetic resonance imaging (MRI) studies based on the ubiquitous expression of ferritin MRI reporter gene in diverse tissues. PROCEDURES: Transgenic mice (TG) expressing myc-tagged human heavy chain ferritin (myc-hFTH) under the control of a ubiquitous CAG promoter were produced. The expression of myc-hFTH in diverse tissues of the myc-hFTH TG was assessed by RT-PCR, Western blotting, and immunohistochemistry. The iron accumulation and the deposition of ferritin aggregates in tissues of myc-hFTH TG and WT were analyzed by Prussian blue staining and transmission electron microscopy. The myc-hFTH TG (n = 9) and wild-type mice (WT) (n = 4) were subjected to MRI on 9.4 T MR scanner. An eight-point T(2)* mapping was performed using a multiple gradient echo sequence, and T(2)* value was estimated pixel by pixel by using a routine least-squares fitting algorithm. RESULTS: We generated the myc-hFTH TG expressing myc-hFTH in brain, heart, liver, lung, spleen, pancreas, kidney, and intestine. The myc-hFTH TG showed no apparent pathological symptoms and no histological changes compared to WT. The expression of myc-hFTH in the brain and liver tissues of myc-hFTH TG led to a significant decrease in T(2)* values, as shown by noninvasive MRI, compared to WT (P < 0.05, TG vs. WT). CONCLUSIONS: This study demonstrates that the novel myc-hFTH TG, which expresses an MRI reporter in many tissues, would be a valuable animal model of FTH-based molecular imaging in which to study potential therapies for cell and tissue grafting using an MRI technique. These mice could also serve to study disease related with iron metabolism.

The Effect of Obstructive Sleep Apnea on DNA Damage and Oxidative Stress

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is associated with repeated hypoxia and re-oxygenation. This characteristic of OSAS may cause oxidative stress and DNA damage. However, the link of OSAS with oxidative stress and DNA damage is still controversial. In the current study, we investigated whether OSAS causes DNA damage using alkaline single-cell gel electrophoresis (comet assay) and measuring oxidative stress by monitoring serum malondialdehyde (MDA) levels. METHODS: From March 2009 to August 2010, 51 patients who underwent polysomnography (PSG) during the night were enrolled in this study. We obtained serum from the patients at 6 AM. DNA damage and oxidative stress were evaluated using a comet assay and measuring serum MDA, respectively. We divided the patients into two groups according to the existence of comets appearing in the comet assay. Group 1 included 44 patients with negative assay results and group 2 consisted of seven patients with positive comet assay findings. We compared the age, gender proportion, PSG data (respiratory disturbance index [RDI], lowest O2 saturation level, and arousal index [AI]), time of disease onset, smoking habits, and serum MDA levels between the two groups. RESULTS: The average age and gender proportion of the two groups were not statistically different (P>0.05). The average of RDI for group 1 was 30.4+/-18.4 and 8.0+/-7.7 (P0.05). No relationship between positive comet assay results and OSAS severity was identified. CONCLUSION: Results of the current study showed that OSAS was not associated with DNA damage as measured by comet assays or oxidative stress according to serum MDA levels.

Clinical and Physical Characteristics That Affect Apnea-Hypopnea Index in Suspected Obstructive Sleep Apnea Patients : The Preliminary Study

OBJECTIVES: The purpose of this study is to find the influential clinical and physical characteristics which affect apnea-hypopnea index (AHI) in suspected obstructive sleep apnea (OSA) patients. METHODS: We evaluated the comprehensive factors including sleep related symptoms, clinical scales, medical history, substance use, and anthropometric data of the 119 participants who complained of the symptoms of OSA. All the participants underwent attended-full night laboratory polysomnography. The correlation and multiple regression analysis were conducted to find the influential and predictive factors of AHI. RESULTS: A multiple linear regression model 1 showed that higher AHI was associated with higher body mass index (BMI)(p < 0.001) and higher frequency of observed apnea (p = 0.002). In multiple linear regression model 2, AHI was associated with higher BMI (p < 0.001) and loudness of snoring (p = 0.018). CONCLUSIONS: The present preliminary results suggest that BMI and observed apnea are most influential factors that affect AHI in suspected OSA patients. In the future study we will design the prediction formula for the OSA and AHI, which is useful in the clinical medical field.

A Case of Intraosseous Hemangioma of the Maxilla Bone / 대한이비인후과학회지

Intraosseous hemangioma is a rare tumor, occurring especially in the maxilla. Because hemangioma is a benign tumor with increased vascularity, some authors call it hamartoma. This tumor originates and expands into bony structures. We experienced a female patient with intraosseous hemangioma of the right maxilla. The tumor was completely removed through a gingivobuccal incision and the feeding vessel was embolized. We report this case regarding the radiologic work-up, differential diagnosis, pathology and treatment with a brief review of the literature.

Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition.

Post-translational modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is linked the development of diabetic cardiomyopathy. We investigated whether Nkx2.5 protein, a cardiac transcription factor, is regulated by O-GlcNAc. Recombinant Nkx2.5 (myc-Nkx2.5) proteins were reduced by treatment with the O-GlcNAcase inhibitors STZ and O-(2-acetamido-2-deoxy-D-glucopyroanosylidene)-amino-N-phenylcarbamate; PUGNAC) as well as the overexpression of recombinant O-GlcNAc transferase (OGT-flag). Co-immunoprecipitation analysis revealed that myc-Nkx2.5 and OGT-flag proteins interacted and myc-Nkx2.5 proteins were modified by O-GlcNAc. In addition, Nkx2.5 proteins were reduced in the heart tissue of streptozotocin (STZ)-induced diabetic mice and O-GlcNAc modification of Nkx2.5 protein increased in diabetic heart tissue compared with non-diabetic heart. Thus, excessive O-GlcNAcylation causes downregulation of Nkx2.5, which may be an underlying contributing factor for the development of diabetic cardiomyopathy.

Facile preparation of zwitterion-stabilized superparamagnetic iron oxide nanoparticles (ZSPIONs) as an MR contrast agent for in vivo applications.

We describe a simple method for synthesizing superparamagnetic nanoparticles (SPIONs) as small, stable contrast agents for magnetic resonance imaging (MRI) based on sulfobetaine zwitterionic ligands. SPIONs synthesized by thermal decomposition were coated with zwitterions to impart water dispersibility and high in vivo stability through the nanoemulsion method. Zwitterion surfactant coating layers are formed easily on oleic acid-stabilized SPIONs via hydrophobic and van der Waals interactions. Our zwitterion-coated SPIONs (ZSPIONs) had ultrathin (∼5 nm) coating layers with mean sizes of 12.0 ± 2.5 nm, as measured by dynamic light scattering (DLS). Upon incubation in 1 M NaCl and 10% FBS, the ZSPIONs showed high colloidal stabilities without precipitating, as monitored by DLS. The T2 relaxivity coefficient of the ZSPIONs, obtained by measuring the relaxation rate on the basis of the iron concentration, was 261 mM(-1) s(-1). This value was much higher than that of the commercial T2 contrast agent because of the ultrathin coating layer. Furthermore, we confirmed that ZSPIONs can be used as MR contrast agents for in vivo applications such as tumor imaging and lymph node mapping.