Dong H. Lee

Is normosmic Parkinson disease a unique clinical phenotype

Objective: Olfactory dysfunction is present in the majority of patients with early-stage Parkinson disease (PD) and can precede the onset of motor symptoms by many years. We performed this study to evaluate whether normosmic patients with PD had different clinical features compared to hyposmic patients. Methods: We analyzed the data of 208 de novo patients with PD (mean age, 65.4 ± 9.7 years; range, 38–85 years; 104 men) who underwent both olfactory function tests and dopamine transporter (DAT) scans. Results: Normosmic patients were significantly younger and had fewer motor deficits than hyposmic patients with PD. Striatal subregional DAT activities were comparable between the 2 groups, but intersubregional gradients were significantly higher in normosmic than hyposmic PD. A general linear model showed that normosmic patients with PD showed significantly fewer motor deficits after controlling the patients age, sex, symptom duration, and DAT activity in the posterior putamen (p = 0.016). Levodopa-equivalent dose at approximately 2.5 years follow-up tended to be lower in normosmic than in hyposmic PD (p = 0.055). Conclusions: These results suggest that normosmic PD is a unique clinical phenotype with a more benign course, compared to hyposmic PD. Either less pathologic involvement in the olfactory system or a greater potential for olfactory neurogenesis in normosmic PD may contribute to this benign process compared to hyposmic PD.

P. aeruginosa Infection Increases Morbidity in Experimental Cholesteatomas

Clinicians have long noted that infected cholesteatomas are more aggressive than uninfected ones without data to support these observations. The purpose of this study is to determine the etiological role of biofilm forming P. aeruginosa (PA) and the virulence factor, type IV pili (TFP), in the pathogenesis of experimental cholesteatomas.

Association of body mass index and the depletion of nigrostriatal dopamine in Parkinson's disease

Several antecedent studies had reported close relationship between low body weight and Parkinsons disease (PD). However, there have been few investigations about the role of body weight to nigrostriatal dopaminergic neurodegeneration. This study enrolled 398 de novo patients with PD whom underwent [18F] N-(3-Fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography scan and body mass index (BMI) measurement. The relationships between BMI and dopamine transporter (DAT) activity were analyzed using linear regression analysis. A multivariate analysis adjusted for age, gender, disease duration, smoking status, coffee and tea consumption, and residence area revealed that BMI remained independently and significantly associated with DAT activity in all striatal subregions. Moreover, multiple logistic regression analyses showed that BMI was a significant predictor for the lowest quartile of DAT activity in the anterior putamen, ventral striatum, caudate nucleus, and total striatum. The present findings suggest that a low BMI might be closely associated with low density of nigrostriatal dopaminergic neurons in PD, which could support the evidence for the role of low body weight to PD-related pathologies.

Effect of Dielectric Barrier Discharge Treatment of Blood Plasma to Improve Rheological Properties of Blood

The whole blood viscosity (WBV) is one of the major independent indicators for the risk of cardiovascular disease, stroke, and peripheral arterial diseases. Furthermore, oxidized LDL molecules are known to cause atherosclerotic plaques in arteries, and it is one of the key components that increase WBV. The present study attempted to reduce WBV by coagulating plasma proteins and lipid molecules from blood plasma using non-thermal dielectric barrier discharge (DBD) and removing them through filtration. The DBD treatment was found to produce coagulated particles in blood plasma. After filtration of the coagulated particles, WBV decreased by 9.1 and 17.7% for both systolic and diastolic blood viscosities, respectively. The present results suggest that the removal of excess plasma proteins and lipid molecules might be feasible using DBD treatment.

Successful Posttransplant Treatment of Hepatitis C with Ledipasvir-Sofosbuvir in HIV+ Kidney Transplant Recipients.

Background Ledipasvir-sofosbuvir is effective at eradicating hepatitis C virus (HCV) infection in the general population and in HCV-monoinfected kidney transplant recipients, but there are no data to guide its use in human immunodeficiency virus/HCV coinfected kidney transplant patients. Methods We treated 6 human immunodeficiency virus/HCV coinfected kidney transplant recipients with ledipasvir-sofosbuvir at our 2 centers. All were infected with genotype 1 and 66% had received kidneys from HCV+ donors. Results All patients cleared the virus while on therapy and 100% have achieved a sustained virologic response at 12 weeks after completion of ledipasvir-sofosbuvir. Tacrolimus dosing required adjustment during and after ledipasvir-sofosbuvir therapy but antiretroviral regimens did not. Conclusions Ledipasvir-sofosbuvir was well tolerated. Although all patients in our series were treated posttransplant, the ideal timing of HCV therapy in this population is unknown, and the impact of HCV clearance on posttransplant outcomes is yet to be determined.

Radiographic and micro-computed tomographic imaging of lipopolysaccharide-mediated bone resorption.

Objectives: Chronic otitis media and cholesteatomas cause hearing loss as a result of bony erosion. This bone resorption is known to be more aggressive when cholesteatomas become infected. The most common organism isolated from both diseases is the gram-negative bacterium Pseudomonas aeruginosa. Lipopolysaccharide (LPS), a major virulence factor found in the gram-negative bacterial cell wall, is well known to incite inflammatory bone resorption. The mechanisms underlying this process, however, are poorly understood. In this study, we developed a mouse model of calvarial osteolysis in which resorption was reliably imaged by plain radiography and micro–computed tomography (micro-CT). Methods: A murine calvarial model was developed to study bone resorption induced by P aeruginosa LPS. Calvariae from wild-type and knockout mice used in this model were imaged by plain radiography and micro-CT. Results: A high degree of correlation between plain radiography and micro-CT was identified (R2 = 0.8554). Furthermore, maximal LPS-induced bone resorption required functioning toll-like receptor (TLR) 2, TLR4, and myeloid differentiation factor 88 (MyD88). Conclusions: We have developed a successful model of inflammatory osteolysis in which plain radiography can reliably delineate induced bone resorption. In vivo, we have shown that P aeruginosa LPS signals via TLR2, as well as TLR4 through MyD88.

Serum creatinine elevation after switch to dolutegravir in a human immunodeficiency virus–positive kidney transplant recipient

Dolutegravir is a preferred antiretroviral drug for human immunodeficiency virus (HIV)‐infected patients following solid organ transplantation. It has potent antiretroviral activity and does not interact with calcineurin inhibitors. We describe a case of an HIV‐infected kidney transplant patient, who was noted to have a rising serum creatinine following initiation of dolutegravir. At first, an acute rejection episode was suspected, but this finding was later attributed to inhibition of creatinine secretion by dolutegravir. We suggest that an awareness of this potential effect of dolutegravir is important for providers who take care of HIV‐positive kidney transplant recipients, in order to prevent potentially unnecessary testing.

Barriers to listing for HIV-infected patients being evaluated for kidney transplantation

Human immunodeficiency virus (HIV)‐infected patients have excellent outcomes following kidney transplantation (KT) but still might face barriers in the evaluation and listing process. The aim of this study was to characterize the patient population, referral patterns, and outcomes of HIV‐infected patients who present for KT evaluation. We performed a single‐center retrospective cohort study of HIV‐infected patients who were evaluated for KT. The primary outcome was time to determination of eligibility for KT. Between 2011 and 2015, 105 HIV‐infected patients were evaluated for KT. Of the 105 patients, 73 were listed for transplantation by the end of the study period. For those who were deemed ineligible, the most common reasons cited were active substance abuse (n = 7, 22%) and failure to complete the full transplant evaluation (n = 7, 22%). Our cohort demonstrated a higher proportion of HIV‐infected patients eligible for KT than in previous studies, likely secondary to advances in HIV management. Among those who were denied access to transplantation, we identified that many were unable to complete the evaluation process, and that active substance abuse was common. Future prospective studies should examine reasons and potential interventions for the lack of follow‐through and drug use we observed in this population.

Spatial distribution of polycyclic aromatic hydrocarbon and polychlorinated biphenyl sources in the Nakdong River Estuary, South Korea.

ABSTRACT Our research team investigated the elemental composition and the presence of various toxic organic compounds, such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), in estuary surface sediments to trace the spatial distribution of the sources of pollution deposited in Nakdong River, Busan, South Korea. The spatial patterns of elemental composition and toxic organic compounds were determined from the measurements of total organic carbon (TOC), total nitrogen, total sulfur, PAHs, and PCBs. The sediments had TOC contents of between 0.02 and 1.80 wt% (avg. 0.34 wt%), depending on the amount of clay-sized particles. The concentrations of PAHs and PCBs (10.8–167.7 ng g−1 dry wt and 197.0–754.0 pg g−1 dry wt, respectively) in surface sediments revealed different spatial patterns for these compounds, suggesting that they partially originated from the combustion of fossil fuels and from the use of commercial PCB products at adjacent industrial complexes. Although these concentrations were far below the Sediment Quality Guideline (SQG) of the National Oceanic and Atmospheric Administration (NOAA), the sediments at one site contained PCBs at concentrations close to the response level (754.0 pg g−1 dry wt), and were dominated by low-molecular-weight PAHs. The PAHs and PCBs in Nakdong River Estuary sediments were likely to have originated from the combustion of fossil fuels and biomass at the adjacent industrial complexes. The primarily analyzed results determined that PAHs originated from the combustion of fossil fuels and biomass, and overall concentrations were related to the contributions of individual PAHs in most sediment samples. Based on the SQG of the NOAA, our results indicate that the anthropogenic activity should be considered on the future-sustainable management of this estuary system.

A rare case of disseminated Mycobacterium avium complex with colitis in a renal transplant recipient

Mycobacterium avium complex (MAC) colitis is a rare complication of immunosuppression in solid organ transplant (SOT) recipients. Here, we describe a case of disseminated MAC infection with colitis following renal transplantation. Despite common pathways of immunosuppression, SOT recipients and human immunodeficiency virus (HIV)‐infected patients differ in their typical presentations of MAC infection. Intestinal infections have been more commonly reported in HIV‐infected patients than in SOT recipients. The explanation for this difference may be related to HIVs targeted effects on the CD4+ T‐cell reservoir in gut‐associated lymphoid tissue.